Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
. CA 02324421 2000-09-26. '
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DESCRIPTION
Method And Rea ents For The Treatment Of
Diseases Or Conditions Related To
Molecules Involved In An io enic Res onses
PCT/US99/06507
Background Of The Invention
This invention relates to methods and reagents for
the treatment of diseases or conditions relating to the
levels of expression of angiogenic factors and receptors
involved in the regulation of angiogenesis.
The following is a discussion of relevant art, none
of which is admitted to be prior art to the present
invention.
The formation of blood vessels in vertebrates can be
described in two embyronic stages. During the first
stage, known as vasculogenesis, yolk sac splanchnopleuric
mesenchyme differentiates into vascular progenitor cells
and then to blood island aggregates which are primitive
blood cells surrounded by fused endothelial progenitors
(angioblasts). These blood islands then fuse and go on to
form a vascular plexus which supplies nutrients to the
embryo (Merenmies et al., 1997, Gel1 Growth & Development
8, 3-10). The next vascular developmental step is known as
angiogenesis. From the vessels formed during
vasculogenesis, new blood vessels sprout, elongate and
develop into capillary loop formations of endothelial
cells. It is a highly complex event involving local
basement membrane disruption, endothelial cell
proliferation, migration and microvessel morphogenesis
(Rak et al., 1995, Anti-Cancer Drugs 6, 3-18). Organs
such as the brain and kidney are vascularized through the
angiogenic process (Dumont et al., 1995, Developmental
Dynamics 203, 80-92).
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Angiogenesis has been described to occur through two
mechanisms, vascular sprouting and intussusception.
Intussusception of pre-existing vessels occur after
proliferation of endothelial cells producing a wide lumen.
Through the utilization of transcapillary pillars or posts
of extracellular matrix, the lumen is split to form two
vessels (Risau, 1997, Nature 386, 671-674). Sprouting
angiogenesis also originates from pre-existing blood
vessels and consists of new blood vessels sprouting,
elongating and developing into capillary loop formations
of endothelial cells. It is a highly complex event
involving disruption of extracellular matrix, endothelial
cell proliferation, chemotaxic migration and microvessel
morphogenesis (Rak, supra). Many factors regulating
positive and negative control of angiogenesis have been
reported demonstrating the sophistication of this process.
An example of an angiogenic factor is Vascular Endothelial
Growth Factor receptor (VEGFr) which has been shown to be
specific to endothelial cells and is discussed in Pavco et
al., Int. PCT Pub. No. WO 97/15662.
Unlike vasculogenesis, angiogenesis not only occurs
in embyronic development, but can also occur throughout
the lifespan of the organism during such events as wound
healing, bone repair, inflammation, and female menstral
cycles. Local delivery of oxygen and nutrients and the
removal of waste requires a complex system of blood
vessels which has the ability to adapt as the tissue
requirements changes. Involvement of a large number of
positive and negative factors in angiogenic regulation
demonstrates the complexity of this process. When the
balance between upregulating factors and downregulating
factors is disrupted in favor of increased angiogenesis,
disease states have been known to occur.
Many factors have been identified which contribute to
increased angiogenesis including:
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1) ryl Hydrocarbon Nuclear Transporter (ARNT): ARNT
(also known as HIF-1(3) forms heterodimers with several
factors including HIF-a(Maxwell et al., 1997, Proc. Natl.
Acad. Sci. USA 94, 8109-8209). When HIF-a and ARNT complex
together, they form a complex called HIF-1. HIF -1 is
believed to be regulate genes involved in the response to
oxygen deprivation. ARNT -/- embryonic stem cells fail to
induce VEGF expression in response to hypoxia. ARNT -/-
mice are not viable beyond embryonic day 10.5. Like VEGF
knockout mice, these embryos show defective angiogenesis
of the yolk sac (Maltepe et al., 1997, Nature 386, 403-
907) .
Hepatoma cells containing an ARNT mutation that is
functionally deficient in dimerizing with HIF-lashows
greatly reduced VEGF expression in response to hypoxia
compared to normal cells (Wood et al., 1996, J. Biol.
Chem. 271, 15117-15123). Tumor xenografts derived from
these cells show reduced vascularity and approximately 2=
fold reduced tumor growth rates (Maxwell et al., 1997,
supra) .
2) Tie-2: Tie-2 (also known as Tek), is a tyrosine
kinase protein receptor which consists of 1122 amino acids
and is produced in endothelial (Merenmies et al., 1997,
Cell Growth & Differentiation 8, 3-10) as well as early
hematopoeitic cells (Maisonpierree et al., 1993, Oncogene
8, 1631-1637). Tie-2 expression has been demonstrated in
mice, rats and humans. The human gene is thought to be
located on chromosome 9p21 (Dumont et al., 1994, Genes &
Development 8, 1897-1909). Tie-2 homozygous mutant
endothelial cells were examined using anti-PECAM
monoclonal antibody (Sato et al., 1997, Nature 376, 70-
74). All of the homozygous mutants were dead within 10.5
days with obvious deformities in the head and heart
present by day 9.5. In addition, large vessels were
indistinguishable from small vessels and no capillary
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sprouts were seen in the brain. These observations
suggested that Tie-2 plays an important role in
angiogenesis rather than vasculogenesis. The earlier
effects of Tie-2 mutant compared to the Tie-1 mutant
indicates separate roles for the two RTK's in
angiogenesis.
Ligands to Tie-2 have been discovered and named'
angiopoietin 1 and 2 (angl and 2) (Davis, S. et al., 1993,
Cell 87, 1161; Maisonpierre, P.C. et a1.,1997, Science,
277, 55-60). Both factors consist of an NH2-terminal
coiled-coil domain as well as a COOH-terminal fibrinogen-
like domain. Angl binds to Tie-2/Tek but not Tie-1 and
stimulates angiogenesis through autophosphorylation. Ang2
is a 496 amino acid polypeptide whose human and mouse
homologs are 85$ identical. Autophosphorylation caused by
Angl binding to the Tie-2 receptor can be blocked with the
addition of Ang2. The Tie-2 receptor is unusual in that it
utilizes both positive and negative control mechanisms.
3) Integrins: Integrins are a family of cell
adhesion and migration mediating proteins that are
comprised of at least 15 alpha and 8 beta subunits that
are expressed as a number of different a(3 non-covalently
bound heterodimers on cell surfaces (Varner, 1997,
Regulation of Angiogenesis, ed I.D Goldberg & E.M. Rosen,
361-390; Brooks, 1996, Eur J Cancer 14, 2423-2429). Each
combination of integrin subunits is thought to have
angiogenic capabilities, for example a6(31 has been
implicated in capillary tube formation Additionally,
distinct integrins allow for the attachment to many
different extracellular matrix (ECM) components including
fibronectin, vitronectin, laminin and collagen (Stromblad
& Cheresh, 1996, Chemistry & Biochemistry 3, 881-885).
Integrin production has been shown to be induced by a
number a stimuli including intracellular pH increases,
calcium concentration, inositol lipid synthesis, tyrosine
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phosphorylation of a focal contact associated tyrosine
kinase, and activation of p34/cdc2 and cyclin A (Varner &
Cheresh, 1996, Curr Op in Cell Bio1 8,724-730).
a"[33 a 160kDa protein is the most well characterized
5 molecule of the integrin family and is believed to play a
large role in angiogenesis (Varner, 1997, supra). a~(33
binds the largest number of ECM components of all known
heterodimers indicating any cell with these molecules on
the cell surface could adhere to or migrate on almost any
of the ECM components (Varner, 1997, supra). When
vascular endothelial cells are in their quiescent state
very little a~(33 is expressed, but is highly upregulated in
several pathological conditions including neoplasms.
Antagonists to a"(33 can inhibit angiogenesis in the chick
chorioallentoic membrane (CAM) model and in SCID mice and
even reduce the tumor volume. When antibodies are
administered for A"(33, apoptosis is observed in the
proliferating vascular vessels. This has led to
suggestions that a"~33 provides a survival signal for
vascular cells allowing for continued proliferation
(Stromblad & Cheresh, 1996, supra; Varner, 1997 supra).
Other angiogenic targets are included and their
characteristics are defined in the following references,
all of which are incorporated herein by reference in their
entirety: Methionine Aminopeptidase: (Arfin et al., 1995,
PNAS 92, 7714-7718 (Genbank Accession No. U29607) ; Sin,
N. et.al., 1997, PNAS 94, 6099-6103; Griffith et al.,
1997, Chem Biol. 4(6), 461-471); Transcription factor Ets-
1: (Iwasaka, C. et a1. 1996. J. Cell Phys.iol. 169, 522-531:
Chen, Z. et al. ,1997, Cancer Res. 57, 2013-2019;
Hultgardh-Nilsson A, et al., 1996, Circ Res. 78(4), 589-
595; Reddy et al., 1988, Oncogene Res. 3 (3), 239-246
(Genbank accession No. X14798)); Platelet-derived
endothelial cell growth factor and its receptor (PD-ECGF &
PD-ECGFr): (Furukawa, T. et al., 1992, Nature 356, 668;
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Moghaddam, A. et al., 1995, Proc. Natl. Acad. Sci.; Clark,
R.A.F. et a1. ,1996, Am J. Pathol. 148, 1407; Hoshina,
T.M., et al., 1995, Int. J. Cancer 64, 79-82; Nakanishi,
A.K., et al., 1992, J. Biol. Chem 267, 20311-20316;
Finnis et al., unpublished (Genbank accession No. M63193);
Transforming Growth factors (TGFs): (Schreiber et al.,
1986, Science 232, 1250; Maione, T.E. and Sharpe,
R.J.,1990, Trends Pharm. Sci., 11, 457-461; Noma et al.,
1991, Growth Factors 9 (4), 247-255; Sukurai (unpublished)
(Genbank accession No. AB009356);Transformin growth
factor receptor: (Miyazono, K.,1996, Nippon Yakurigaku
Zasshu 107, 133-140; Mahooti-Brooks. et a1.,1996, J. Clin.
Invest. 97, 1436-1446; Lopez-Casillas et al., 1991, Cell
67 (4 ) , 797-805; Lopez-Casillas et a1. , 1991, Cell 67 (4 ) ,
785-795 (Genbank Accession No. L07594); Angiogenin: (Fett
et al., 1985, Biochemistry 24, 5480-5486; Bicknell &
Vallee, 1988, PNAS 85, 5961-5965; Vallee & Riordan,1988,
Adv. Exp. Med. Bio.I 234, 41-53; Shapiro & Vallee,1987,
PNAS 84, 2238-2241; Shapiro et a.I.,1986, Biochemistry 25,
3527-3532; Olson et al., 1994, Cancer Res. 54, 4576-4579;
Kurachi et al., 1985, Biochemistry 24, 5494-5499; Kurachi
et al., 1985, Biochemistry 24 (20), 5494-5499(Genbank
Accession No. M11567)); Tumor necrosis factor receptor:
(Naismith et a1.,1995,. J. Inflamm 47, 1-7; Loetscher et
al., 1990, Cell 61, 351-359; Himmler et al., 1990, DNA
Cell Biol. 9, 705-715 (Genbank Accession No. M63121
M75861); Endothelial cell stimulating an io enesis factor
(ESAF): (Brown & Weiss,1988,. Ann. Rheum. Dis., 47, 881-
885); Interleukin-8 (IL-8): (Elner et al., 1991, , Am
J. Pathol. 139, 977-988; Strieter et a1.,1992, Am. J.
Pathol. 191, 1279-1284; Mukaida et al., 1989, J. Immunol.
143 (4), 1366-1371(Genbank Accession No. M28130));
Angiopoietin 1: (Davis, S. et a1.,1996, Cel~ 87, 1161;
Iwama, A. et a1.,1993, Biochem Biophys. Res. Commun. 195,
301; Dumont, D.J. et al.,1995, Genes Dev 8, 1897; Sato,
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T.N. et a1.,1995, Nature 376, 70; Suri, C. et al., 1996)
Cell 87, 1171(Genbank Accession No. U83508)); Angiopoietin
2: (Maisonpierre, et a1.,1997, Science, 277, 55-60;
Hanahan, 1997, Science 277, 48-50; Genbank Accession No.
AF004327 (unpublished));Insulin-like growth factor (IGF-
1): (Warren, R.S. et a1.,1996, J. Biol. Chem. 271, 29483-
29488; Grant et.al., 1993,Diabetologia 36, 282-291;
Nicosia et al., 1994, Am. J. Pathol. 145, 1023-1029;
Steenbergh et al., Biochem. Biophys. Res. Commun. 175,
507-514 (Genbank Accession: X57025); Insulin-like growth
factor receptor (IGF-lr): (Ullrich et al., 1986, EMBO J.
5, 2503-2512 (Genbank Accession No. X04439 M24599); B61:
(Pandey, A. et al., 1995, Science 268, 567-569; Holzman et
al., 1990, Mol. Cell. Biol. 10, 5830-5838 (Genbank
Accession No. M57730 M37476); B61 receptor (Eck): (Pandey,
A. et al., 1995, Science 268, 567-569; Lindberg & Hunter,
1990, Mol. Cell. Biol. 10 (12), 6316-6324 (Genbank
Accession No. M59371 M36395); Protein kinase C: (Morris et
al., 1988, Cell Physiol. 23, C318-C322; Oikawa, T. et al.,
20. 1992, J. Antibiot. 45, 1155-1160; Finkenzeller. et al.,
1992, Cancer Res. 52, 4821-4823; Kubo et al., 1987, FEBS
Lett. 223 (1), 138-142 (Genbank Accession No. X06318
M27545): ); SH2 domain (Guo, D. et al., 1995, J. Biol.
Chem 270, 6729-6733)
a. Phospholipase c-g:(Guo, D. at al., 1995, J. Biol.
Chem 270, 6729-6733; Rhee, S.G. et al. (1992) J. Biol.
Chem 267, 12393-12396; Burgess et al., 1990, Mol. Cell.
Biol. 10, 4770-4777 (Genbank Accession No. M34667))
b. Phosphatidylinositol 3 kinase (PI-3): (Downs, C.P.
et a1.,1991, Cell Signalling 3, 501-513; Genbank
accession No. 229090; Genbank accession No. 296973)
c. Ras GTPase activating protein (GAP): (Trahey, M.
et a1.,1987, Science 238, 542-545; Guo, D. et al., 1995,
J. Biol. Chem 270, 6729-6733; Trahey et al., 1988, Science
242, 1697-1700 (Genbank accession No. M23612))
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d. Oncogene adaptor protein Nck:(Park & Rhee, 1992,
Mol. Cell. Biol. 12, 5816-5823; Johnson, 1990, Nucleic
Acids Res. 18 (4), 1048 (Genbank accession No. X17576));
Granulocyte Colony-Stimulating Factor: (Devlin et al.,
1987, J. Leukoc. Biol. 41, 302-306 (Genbank accession No.
M17706)); Hepatocyte growth factor: (Miyazawa et al.,
1991, Eur. J. Biochem. 197 (1), 15-22 (Genbank accession
No. X57574); Proliferin: (Groskopf et al., 1997,
Endocrinology 138(7), 2835-2840; Jackson D, et al., 1994,
Science. 266(5190), 1581-1584; Volpert et al., 1996 ,
Endocrinology 137(9): 3871-3876); Placental growth factor:
(Kodama et al., 1997, Eur J Gynaecol Oncol.; 18(6), 508
510; Ziche et al., 1997, Lab Invest. 76(4), 517-531; Relf
et al., 1997, Cancer Res. 57(5), 963-969; Genbank
accession No. Y09268)
Summary Of The Invention
The invention features the use of enzymatic nucleic
acid molecules and methods for their use to down regulate
or inhibit the expression of angiogenic factors.
Specifically, the enzymatic nucleic acids of the present
invention are used as a treatment for indications relating
to angiogenesis including but not limited to cancer, age
related macular degeneration (ARMD), diabetic retinopathy,
inflammation, arthritis, psoriasis and the like.
In a preferred embodiment, the invention features
enzymatic nucleic acid molecules that cleave RNAs encoding
angiogenic selected from a group comprising: Tie-2,
integrin subunit X33, integrin subunit a6, and aryl
hydrocarbon nuclear transporter (ARNT).
By "inhibit" it is meant that the activity of the
cleaved RNA is reduced below that observed in the absence
of the nucleic acid. In one embodiment, inhibition with
ribozymes preferably is below that level observed in the
presence of an enzymatically inactive. RNA molecule that is
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able to bind to the same site on the mRNA, but is unable
to cleave that RNA.
By "angiogenic factors" is meant a peptide molecule
which is involved in a process or pathway necessary for
the formation of novel blood vessels.
In another preferred embodiment, the invention
features the use of enzymatic nucleic acids that cleave
the RNAs encoded by angiogenic factors selected from a
group comprising: Methionine Aminopeptidase; Ets-1
Transcription factor; integrins; platelet derived
endothelial cell growth factor (PD-ECGF); PD-ECGF
receptor; Transforming Growth factors (TGFs); Transforming
growth factor receptor; Angiogenin; Endothelial cell
stimulating angiogenesis factor (ESAF); Interleukin-8 (IL-
8); Angiopoietin 1 and 2; TIE-1; insulin-like growth
factor (IGF-1); insulin-like growth factor receptor (IGF-
lr); B61; B61 receptor (Eck); Protein kinase C; an SH2
domain. (e.g. Phospholipase c-g, Phosphatidylinositol 3
kinase (PI-3), Ras GTPase activating protein (GAP);
Oncogene adaptor protein Nck; Granulocyte Colony-
Stimulating Factor; Hepatocyte growth factor; Proliferin;
and Placental growth factor.
By "enzymatic nucleic acid" it is meant a nucleic
acid molecule capable of catalyzing reactions including,
but not limited to, site-specific cleavage and/or ligation
of other nucleic acid molecules, cleavage of peptide and
amide bonds, and trans-splicing. Such a molecule with
endonuclease activity may have complementarity in a
substrate binding region to a specified gene target, and
also has an enzymatic activity that specifically cleaves
RNA or DNA in that target. That is, the nucleic acid
molecule with endonuclease activity is able to
intramolecularly or intermolecularly cleave RNA or DNA and
thereby inactivate a target RNA or DNA molecule. This
complementarity functions to allow sufficient
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hybridization of the enzymatic RNA molecule to the target
RNA or DNA to allow the cleavage to occur. 100$
complementarity is preferred, but complementarity as low
as 50-75$ may also be useful in this invention. The
5 nucleic acids may be modified at the base, sugar, and/or
phosphate groups. The term enzymatic nucleic acid is used
interchangeably with phrases such as ribozymes, catalytic
RNA, enzymatic RNA, catalytic DNA, catalytic
oligonucleotides, nucleozyme, DNAzyme, RNA enzyme, endo-
10 ribonuclease, endonuclease, minizyme, leadzyme, oligozyme
or DNA enzyme. All of these terminologies describe
nucleic acid molecules with enzymatic activity. The
specific enzymatic nucleic acid molecules described in the
instant application are not meant to be limiting and those
skilled in the art will recognize that all that is
important in an enzymatic nucleic acid molecule of this
invention is that it have a specific substrate binding
site which is complementary to one or more of the target
nucleic acid regions, and that it have nucleotide
sequences within or surrounding that substrate binding
site which impart a nucleic acid cleaving activity to the
molecule (Cech et al., U.S. Patent No. 4,987,071 Cech et
al., 1988, JAMA).
By "enzymatic portion" or "catalytic domain" is meant
that portion/region of the ribozyme essential for cleavage
of a nucleic acid substrate (for example see Figure 1).
By "substrate binding arm" or "substrate binding
domain" is meant that portion/region of a ribozyme which
is complementary to (i.e., able to base-pair with) a
portion of its substrate. Generally, such complementarity
is 100$, but can be less if desired. For example, as few
as IO bases out of 14 may be base-paired. Such arms are
shown generally in Figure 1. That is, these arms contain
sequences within a ribozyme which are intended to bring
ribozyme and target RNA together through complementary
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base-pairing interactions. The ribozyme of the invention
may have binding arms that are contiguous or non-
contiguous and may be of varying lengths. The length of
the binding arms) are preferably greater than or equal to
four nucleotides; specifically 12-100 nucleotides; more
specifically 14-24 nucleotides long. If two binding arms
are chosen, the design is such that the length of the
binding arms are symmetrical (i.e., each of the binding
arms is of the same length; e.g., five and five
nucleotides, six and six nucleotides or seven and seven
nucleotides long) or asymmetrical (i.e., the binding arms
are of different length; e.g., six and three nucleotides;
three and six nucleotides long; four and five nucleotides
long; four and six nucleotides long; four and seven
nucleotides long; and the like).
By DNAzyme is meant, an enzymatic nucleic acid
molecule lacking a 2'-OH group.
In one of the preferred embodiments, the enzymatic
nucleic acid molecule is formed in a hammerhead or hairpin
motif, but may also be formed in the motif of a hepatitis
8 virus, group I intron, group II intron or RNase P RNA
(in association with an RNA guide sequence), Neurospora VS
RNA or DNAzymes. Examples of such hammerhead motifs are
described by Dreyfus, supra, Rossi et al., 1992, AIDS
Research and Human Retroviruses 8, 183; of hairpin motifs
by Hampel et al., EP0360257, Hampel and Tritz, 1989
Biochemistry 28, 4929, Feldstein et al., 1989, Gene 82,
53, Haseloff and Gerlach, 1989, Gene, 82, 43, and Hampel
et al., 1990 Nucleic Acids Res. 18, 299; of the hepatitis
d virus motif is described by Perrotta and Been, 1992
Biochemistry 31, 16; of the RNaseP motif by Guerrier-
Takada et al., 1983 Cel.I 35, 849; Forster and Altman,
1990, Science 299, 783; Li and Altman, 1996, Nucleic Acids
Res. 24, 835; Neurospora VS RNA ribozyme motif is
described by Collins (Saville and Collins, 1990 Cell 61,
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685-696: Saville and Collins, 1991 Proc. Natl. Acad. Sci.
USA 88, 8826-8830; Collins and Olive, 1993 Biochemistry
32, 2795-2799: Guo and Collins, 1995, EMBO. J. 14, 363);
Group II introns are described by Griffin et al., 1995,
Chem. Biol. 2, 761: Michels and Pyle, 1995, Biochemistry
34, 2965: Pyle et al., International PCT Publication No.
WO 96/22689: of the Group I intron by Cech et al:, U.S.
Patent 4,987,071 and of DNAzymes by Usman et al.,
International PCT Publication No. WO 95/11304; Chartrand
et al., 1995, NAR 23, 4092; Breaker et al., 1995, Chem.
Bio. 2, 655: Santoro et al., 1997, PNAS 94, 4262. These
specific motifs are not limiting in the invention and
those skilled in the art will recognize that all that is
important in an enzymatic nucleic acid molecule of this
invention is that it has a specific substrate binding site
which is complementary to one or more of the target gene
RNA regions, and that it have nucleotide sequences within
or surrounding that substrate binding site which impart an
RNA cleaving activity to the molecule (Cech et al., U.S.
Patent No. 4,987,071).
By "equivalent" RNA to Tie-2, integrin subunit (33,
integrin subunit a6, or ARNT is meant to include those
naturally occurring RNA molecules having homology (partial
or complete) to Tie-2, integrin subunit (33, integrin
subunit a6, or ARNT or encoding for proteins with similar
function as Tie-2, integrin subunit (33, integrin subunit
a6, or ARNT in various animals, including human, rodent,
primate, rabbit and pig. The equivalent RNA sequence also
includes in addition to the coding region, regions such as
5'-untranslated region, 3'-untranslated region, introns,
intron-exon junction and the like.
By "homology" is meant the nucleotide sequence of two
or more nucleic acid molecules is partially or completely
identical.
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By "complementarity" is meant a nucleic acid
molecules that can form hydrogen bonds) with another
nucleic acid sequence by either traditional Watson-Crick
or other non-traditional types (for example, Hoogsteen
type) of base-paired interactions.
In a preferred embodiment the invention provides a
method for producing a class of enzymatic cleaving agents
which exhibit a high degree of specificity for the RNA of
a desired target. The enzymatic nucleic acid molecule is
preferably targeted to a highly conserved sequence region
of a target RNAs encoding Tie-2, integrin subunit (33,
integrin subunit a6, or ARNT proteins such that specific
treatment of a disease or condition can be provided with
either one or several enzymatic nucleic acids. Such
enzymatic nucleic acid molecules can be delivered
exogenously to specific cells as required. Alternatively,
the ribozymes can be expressed from DNA/RNA vectors that
are delivered to specific cells.
By "highly conserved sequence region" is meant a
nucleotide sequence of one or more regions in a nucleic
acid molecule does not vary significantly from one
generation to the other or from one biological system to
the other.
Such ribozymes are useful for the prevention of the
diseases and conditions including cancer, diabetic
retinopathy, macular degeneration, neovascular glaucoma,
myopic degeneration, arthritis, psoriasis, verruca
vulgaris, angiofibroma of tuberous sclerosis, pot-wine
stains, Sturge Weber syndrome, Kippel-Trenaunay-Weber
syndrome, Osler-Weber-Rendu syndrome and any other
diseases or conditions that are related to the levels of
Tie-2, integrin subunit ~i3, integrin subunit a6, or ARNT
activity in a cell or tissue.
By "related" is meant that the inhibition of Tie-2,
integrin subunit X33, integrin subunit a6, and/or ARNT RNAs
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14
and thus reduction in the level respective protein
activity will relieve to some extent the symptoms of the
disease or condition.
In preferred embodiments, the ribozyrnes have binding
arms which are complementary to the target sequences in
Tables III-X. Examples of such ribozymes are also shown
in Tables III-X. Tables III and IV display target
sequences and ribozymes for ARNT, Tables V and VI display
target sequences and ribozymes for Tie-2, tables VII and
VIII display target sequences and ribozymes for integrin
subunit alpha 6, and tables IX and X display target
sequences and ribozymes for integrin subunit beta 3.
Examples of such ribozymes consist essentially of
sequences defined in these Tables.
By "consists essentially of" is meant that the active
ribozyme contains an enzymatic center or core equivalent
to those in the examples, and binding arms able to bind
mRNA such that cleavage at the target site occurs . Other
sequences may be present which do not interfere with such
cleavage.
Thus, in a first aspect, the invention features
ribozymes that inhibit gene expression and/or cell
proliferation. These chemically or enzymatically
synthesized RNA molecules contain substrate binding
domains that bind to accessible regions of their target
mRNAs. The RNA molecules also contain domains that
catalyze the cleavage of RNA. The RNA molecules are
preferably ribozymes of the hammerhead or hairpin motif.
Alternatively, the ribozymes are DNAzymes. Upon binding,
the ribozymes cleave the target mRNAs, preventing
translation and protein accumulation. In the absence of
the expression of the target gene, cell proliferation is
inhibited. Chemically synthesized RNA molecules also
include RNA molecules assembled together from various
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
fragments of RNA using a chemical or an enzymatic ligation
method.
In a preferred embodiment, ribozymes are added
directly, or can be complexed with cationic lipids,
5 packaged within liposomes, or otherwise delivered to
target cells. The nucleic acid or nucleic acid complexes
can be locally administered to relevant tissues ex vivo,
or in vivo through injection, infusion pump or stent, with
or without their incorporation in biopolymers. In another
10 preferred embodiment, the ribozyme is administered to the
site of Tie-2, integrin subunit (33, integrin subunit a6,
or ARNT expression (e. g. tumor cells, endothelial cells)
in an appropriate liposomal vehicle.
In another aspect of the invention, ribozymes that
15 cleave target molecules and inhibit Tie-2, integrin
subunit (33, integrin subunit a6, or ARNT activity are
expressed from transcription units inserted into DNA or
RNA vectors. The recombinant vectors are preferably DNA
plasmids or viral vectors. Ribozyme expressing viral
vectors could be constructed based on, but not limited to,
adeno-associated virus, retrovirus, adenovirus, or
alphavirus. Preferably, the recombinant vectors capable of
expressing the ribozymes are delivered as described above,
and persist in target cells. Alternatively, viral vectors
may be used that provide for transient expression of
ribazymes. Such vectors might be repeatedly administered
as necessary. Once expressed, the ribozymes cleave the
target RNA. Delivery of ribozyme expressing vectors could
be systemic, such as by intravenous or intramuscular
administration, by administration to target cells ex-
planted from the patient followed by reintroduction into
the patient, or by any other means that would allow for
introduction into the desired target cell (for a review
see Couture and Stinchcomb, 1996, TIG., 12, 510). In
another aspect of the invention, ribozymes that cleave
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WO 99/50403 PC'T/US99/06507
16
target molecules and inhibit cell proliferation are
expressed from transcription units inserted into DNA, RNA,
or viral vectors. Preferably, the recombinant vectors
capable of expressing the ribozymes are locally delivered
as described above, and transiently persist in smooth
muscle cells. However, other mammalian cell vectors that
direct the expression of RNA may be used for this purpose.
By "patient" is meant an organism which is a donor or
recipient of explanted cells or the cells themselves.
"Patient" also refers to an organism to which enzymatic
nucleic acid molecules can be administered. Preferably, a
patient is a mammal or mammalian cells . More preferably,
a patient is a human or human cells.
By "vectors" is meant any nucleic acid- and/or viral-
based technique used to deliver a desired nucleic acid.
These ribozymes, individually, or in combination or
in conjunction with other drugs, can be used to treat
diseases or conditions discussed above. For example, to
treat a disease or condition associated with Tie-2,
integrin subunit X33, integrin subunit a6, or ARNT, the
patient may be treated, or other appropriate cells may be
treated, as is evident to those skilled in the art.
In a further embodiment, the described ribozymes can
be used in combination with other known treatments to
treat conditions or diseases discussed above. For
example, the described ribozymes could be used in
combination with one or more known therapeutic agents to
treat cancer.
In preferred embodiments, the ribozymes have binding
arms which are complementary to the sequences in the
tables, shown as Seq. I.D. Nos. 394-786, 849-910, 1612
2312, 2381-2448, 3588-4726, 4821-4914, 5702-6488, and
6569-6648. Examples of such ribozymes are shown as Seq.
I.D. Nos.l-393, 787-848, 911-1611, 2313-2380, 2449-3587,
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WO 99/50403 PCT/US99/06507
17
4727 -4820. 4915-5701, and 6489-6568. Other sequences may
be present which do not interfere with such cleavage.
Other features and advantages of the invention will
be apparent from the following description of the
preferred embodiments thereof, and from the claims.
Description Of The Preferred Embodiments
The drawings will first briefly be described.
Figure 1 shows the secondary structure model for
seven different classes of enzymatic nucleic acid
molecules. Arrow indicates the site of cleavage. -------
- indicate the target sequence. Lines interspersed with
dots are meant to indicate tertiary interactions. - is
meant to indicate base-paired interaction. Group I
Intron: P1-P9.0 represent various stem-loop structures
(Cech et al., 1994, Nature Struc. Bio., I, 273). RNas~ P
(M1RNA): EGS represents external guide sequence (Forster
et al., 1990, Science, 249, 783; Pace et al., 1990, J.
Biol. Chem., 265, 3587). Group II Intron: 5'SS means 5'
splice site; 3'SS means 3'-splice site; IBS means intron
binding site; EBS means exon binding site (Pyle et al.,
1994, Biochemistry, 33, 2716). VS RNA: I-VI are meant to
indicate six stem-loop structures; shaded regions are
meant to indicate tertiary interaction (Collins,
International PCT Publication No. W0 96/19577). HDV
Ribozyme: . I-IV are meant to indicate four stem-loop
structures (Been et al., US Patent No. 5,625,047).
Hammerhead Ribozyme: . I-III are meant to indicate three
stem-loop structures; stems I-III can be of any length and
may be symmetrical or asymmetrical (Usman et al., 1996,
Curr. Op. Struct. Bio., 1, 527). Hairpin Ribozyme: Helix
1, 4 and 5 can be of any length; Helix 2 is between 3 and
8 base-pairs long; Y is a pyrimidine; Helix 2 (H2) is
provided with a least 4 base pairs (i.e., n is 1, 2, 3 or
4) and helix 5 can be optionally provided of length 2 or
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
18
more bases (preferably 3 - 20 bases, i.e., m is from 1 -
20 or more). Helix 2 and helix 5 may be covalently linked
by one or more bases (i.e., r is z 1 base). Helix 1, 4 or
may also be extended by 2 or more base pairs (e.g., 4 -
5 20 base pairs) to stabilize the ribozyme structure,' and
preferably is a protein binding site. In each instance,
each N and N' independently is any normal or modified base
and each dash represents a potential base-pairing
interaction. These nucleotides may be modified at the
sugar, base or phosphate. Complete base-pairing is not
required in the helices, but is preferred. Helix 1 and 4
can be of any size (i.e., o and p is each independently
from 0 to any number, e.g., 20) as long as some base-
pairing is maintained. Essential bases are shown as
specific bases in the structure, but those in the art will
recognize that one or more may be modified chemically
(abasic, base, sugar and/or phosphate modifications) or
replaced with another base without significant effect.
Helix 4 can be formed from two separate molecules, i.e.,
without a connecting loop. The connecting loop when
present may be a ribonucleotide with or without
modifications to its base, sugar or phosphate. "q" is Z
2 bases. The connecting loop can also be replaced with a
non-nucleotide linker molecule. H refers to bases A, U,
or C. Y refers to pyrimidine bases. " " refers to a
covalent bond. (Burke et al., 1996, Nucleic Acids & Mol.
eiol., 10, 129; Chowrira et al., US Patent No. 5,631,359).
Figure 2 is a diagrammatic representation of a
hammerhead ribozyme targeted against Tie-2 at position
1037.
Enzymatic Nucleic Acid Molecules
Seven basic varieties of naturally-occurring
enzymatic RNAs are known presently. In addition, several
in vitro selection (evolution) strategies (Orgel, 1979,
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
19
Proc. R. Soc. London, B 205, 435) have been used to evolve
new nucleic acid catalysts capable of catalyzing cleavage
and ligation of phosphodiester linkages (Joyce, 1989,
Gene, 82, 83-87; Beaudry et al., 1992, Science 257, 635-
641; Joyce, 1992, Scientific American 267, 90-97; Breaker
et al., 1994, TIBTECH 12, 268; Bartel et a1.,1993, Science
261:1411-1418; Szostak, 1993, TIBS 17, 89-93; Kumar et
al., 1995, FASEB J., 9, 1183; Breaker, 1996, Curr. Op.
Biotech., 7, 442; Santoro et al., 1997, Proc. Natl. Acad.
Sci., 94, 4262; Tang et al., 1997, RNA 3, 914; Nakamaye &
Eckstein, 1994, supra; Long & Uhlenbeck, 1994, supra;
Ishizaka et al., 1995, supra; Vaish et al., 1997,
Biochemistry 36, 6495; all of these are incorporated by
reference herein). Each can catalyze a series of
reactions including the hydrolysis of phosphodiester bonds
in traps (and thus can cleave other RNA molecules) under
physiological conditions. Table I summarizes some of the
characteristics of some of these ribozymes. In general,
enzymatic nucleic acids act by first binding to a target
RNA. Such binding occurs through the target binding
portion of an enzymatic nucleic acid which is held in
close proximity to an enzymatic portion of the molecule
that acts to cleave the target RNA. Thus, the enzymatic
nucleic acid first recognizes and then binds a target RNA
through complementary base-pairing, and once bound to the
correct site, acts enzymatically to cut the target RNA.
Strategic cleavage of such a target RNA will destroy its
ability to direct synthesis of an encoded protein. After
an enzymatic nucleic acid has bound and cleaved its RNA
target, it is released from that RNA to search for another
target and can repeatedly bind and cleave new targets.
The enzymatic nature of a ribozyme is advantageous
over other technologies, since the concentration of
ribozyme necessary to affect a therapeutic treatment is
lower. This advantage reflects the ability of the
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/0650'1
ribozyme to act enzymatically. Thus, a single ribozyme
molecule is able to cleave many molecules of target RNA.
In addition, the ribozyme is a highly specific inhibitor,
with the specificity of inhibition depending not only on
5 the base-pairing mechanism of binding to the target RNA,
but also on the mechanism of target RNA cleavage. Single
mismatches, or base-substitutions, near the site of
cleavage can be chosen to completely eliminate catalytic
activity of a ribozyme.
10 Nucleic acid molecules having an endonuclease
enzymatic activity are able to repeatedly cleave other
separate RNA molecules in a nucleotide base sequence-
specific manner. Such enzymatic nucleic acid molecules
can be targeted to virtually any RNA transcript, and
15 efficient cleavage achieved in vitro (Zaug et al., 324,
Nature 429 1986 ; Uhlenbeck, 1987 Nature 328, 596; Kim et
al., 84 Proc. Natl. Acad. Sci. USA 8788, 1987; Dreyfus,
1988, Einstein Quart. J. Bio. Med., 6, 92;_ Haseloff and
Gerlach, 339 Nature 585, 1988; Cech, 260 JAMA 3030, 1988;
20 and Jefferies et al., 17 Nucleic Acids Research 1371,
1989; Santoro et al., 1997 supra).
Because of their sequence-specificity, trans-cleaving
ribozymes show promise as therapeutic agents for human
disease (Usman & McSwiggen, 1995 Ann. Rep. Med. Chem. 30,
285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38,
2023-2037). Ribozymes can be designed to cleave specific
RNA targets within the background of cellular RNA. Such a
cleavage event renders the RNA non-functional and
abrogates protein expression from that RNA. In this
manner, synthesis of a protein associated with a disease
state can be selectively inhibited.
Ribozymes that cleave the specified sites in Tie-2,
integrin subunit (33, integrin subunit a6, and aryl
hydrocarbon nuclear transporter (ARNT) mRNAs represent a
novel therapeutic approach to treat cancer, macular
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
21
degeneration, diabetic retinopathy, inflammation,
psoriasis and other diseases. Applicant indicates that
ribozymes are able to inhibit the activity of Tie-2;
integrin subunit (33; integrin subunit a6; and aryl
hydrocarbon nuclear transporter (ARNT) and that the
catalytic activity of the ribozymes is required for their
inhibitory effect. Those of ordinary skill in the art
will find that it is clear from the examples described
that other ribozymes that cleave Tie-2, integrin subunit
(33, integrin subunit a6, and aryl hydrocarbon nuclear
transporter (ARNT) mRNAs may be readily designed and are
within the scope of the invention.
Target sites
Targets for useful ribozymes can be~ determined as
disclosed in Draper et al., WO 93/23569; Sullivan et al.,
WO 93/23057; Thompson et al., WO 94/02595; Draper et al.,
WO 95/04818; McSwiggen et al., US Patent No. 5,525,968 and
hereby incorporated by reference herein in totality.
Rather than repeat the guidance provided in those
documents here, below are provided specific examples of
such methods, not limiting to those in the art. Ribozymes
to such targets are designed as described in those
applications and synthesized to be tested in vitro and in
vivo, as also described. Such ribozymes can also be
optimized and delivered as described therein.
The sequence of human Tie-2, integrin subunit (33,
integrin subunit a6, and aryl hydrocarbon nuclear
transporter (ARNT) mRNAs were screened for optimal
ribozyme target sites using a computer folding algorithm.
Hammerhead or hairpin ribozyme cleavage sites were
identified. These sites are shown in Tables III-X (All
sequences are 5' to 3' in the tables) The nucleotide base
position is noted in the Tables as that site to be cleaved
by the designated type of ribozyme. The nucleotide base
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
22
position is noted in the tables as that site to be cleaved
by the designated type of ribozyme.
Hammerhead or hairpin ribozymes were designed that
could bind and were individually analyzed by computer
folding (Jaeger et al., 1989 Proc. Natl. Acad. Sci. USA,
86, 7706) to assess whether the ribozyme sequences fold
into the appropriate secondary structure. Those ribozymes
with unfavorable intramolecular interactions between the
binding arms and the catalytic core are eliminated from
consideration. Varying binding arm lengths can be chosen
to optimize activity. Generally, at least 5 bases on each
arm are able to bind to, or otherwise interact with, the
target RNA. Ribozymes of the hammerhead or hairpin motif
were designed to anneal to various sites in the mRNA
message. The binding arms are complementary to the target
site sequences described above.
Ribozyme Synthesis
Synthesis of nucleic acids greater than 100
nucleotides in length is difficult using automated
methods, and the therapeutic cost of such molecules is
prohibitive. In this invention, small nucleic acid motifs
(e.g., antisense oligonucleotides, hammerhead or the
hairpin ribozymes) are used for exogenous delivery. The
simple structure of these molecules increases the ability
of the nucleic acid to invade targeted regions of the mRNA
structure. However, these nucleic acid molecules can also
be expressed within cells from eukaryotic promoters (e. g.,
Izant and Weintraub, 1985 Science 229, 345; McGarry and
Lindquist, 1986 Proc. Natl. Acad. Sci. USA 83, 399;
Sullenger Scanlon et al., 1991, Proc. Natl. Acad. Sci.
USA, 88, 10591-5~ Kashani-Sabet et al., 1992 Antisense
Res. Dev., 2, 3-15; Dropulic et al., 1992 J. Virol, 66,
1432-41; Weerasinghe et al., 1991 J. Virol, 65, 5531-4;
Ojwang et al., 1992 Proc. Natl. Acad. Sci. USA 89, 10802-
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WO 99/50403 PCT/US99/06507
23
6; Chen et al., 1992 Nucleic Acids Res., 20, 4581-9;
Sarver et al., 1990 Science 247, 1222-1225; Thompson et
al., 1995 Nucleic Acids Res. 23, 2259). Those skilled in
the art realize that any nucleic acid can be expressed in
eukaryotic cells from the appropriate DNA/RNA vector. The
activity of such nucleic acids can be augmented by their
release from the primary transcript by a ribozyme (Draper
et al., PCT W093/23569, and Sullivan et al., PCT
W094/02595, both hereby incorporated in their totality by
reference herein; Ohkawa et al., 1992 Nucleic Acids Symp.
Ser., 27, 15-6; Taira et al., 1991, Nucleic Acids Res.,
19, 5125-30; Ventura et al., 1993 Nucleic Acids Res., 21,
3249-55; Chowrira et al., 1994 J. Biol. Chem. 269, 25856).
The ribozymes were chemically synthesized. The method
of synthesis used follows the procedure for normal RNA
synthesis as described in Usman et al., 1987 J. Am. Chem.
Soc., 109, 7845; Scaringe et al., 1990 Nucleic Acids Res.,
18, 5433; and Wincott et al., 1995 Nucleic Acids Res. 23,
2677-2684 and makes use of common nucleic acid protecting
and coupling groups, such as dimethoxytrityl at the 5'-
end, and phosphoramidites at the 3'-end. In a non-
limiting example, small scale synthesis were conducted on
a 394 Applied Biosystems, Inc. synthesizer using a
modified 2.5 umol scale protocol with a 5 min coupling
step for alkylsilyl protected nucleotides and 2.5 min
coupling step for 2'-O-methylated nucleotides. Table II
outlines the amounts, and the contact times, of the
reagents used in the synthesis cycle. A 6.5-fold excess
(163 uL of 0.1 M = 16.3 pmol) of phosphoramidite and a 29-
fold excess of S-ethyl tetrazole (238 uL of 0.25 M = 59.5
umol) relative to polymer-bound 5'-hydroxyl was used in
each coupling cycle. Average coupling yields on the 394
Applied Biosystems, Inc. synthesizer, determined by
colorimetric quantitation of the trityl fractions, were
97.5-99~. Other oligonucleotide synthesis reagents for the
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WO 99/50403 PCT/US99/06507
24
394 Applied Biosystems, Inc. synthesizer . detritylation
solution was 2~ TCA in methylene chloride (ABI); capping
was performed with 16~ N-methyl imidazole in THF (ABI) and
10~ acetic anhydride/10$ 2,6-lutidine in THF (ABI);
oxidation solution was 16.9 mM I2, 49 mM pyridine, 9$
water in THF (Millipore). B & J Synthesis ~ Grade
acetonitrile was used directly from the reagent bottle. S
Ethyl tetrazole solution (0.25 M in acetonitrile) was made
up from the solid obtained from American International
Chemical, Inc.
Deprotection of the RNA was performed as follows. The
polymer-bound oligoribonucleotide, trityl-off, was
transferred from the synthesis column to a 4mL glass screw
top vial and suspended in a solution of methylamine (MA)
at 65 °C for 10 min. After cooling to -20 °C, the
supernatant was removed from the polymer support. The
support was washed three times with 1.0 mL of
EtOH:MeCN:H20/3:1:1, vortexed and the supernatant was then
added to the first supernatant. The combined supernatants,
containing the oligoribonucleotide, were dried to a white
powder.
The base-deprotected oligoribonucleotide was
resuspended in anhydrous TEA~HF/NMP solution (250 uL of a
solution of l.5mL N-methylpyrrolidinone, 750 uL TEA and
1.0 mL TEA~3HF to provide a 1.4M HF concentration) and
heated to 65°C for . 1.5 h. The resulting, fully
deprotected, oligomer was quenched with 50 mM TEAB (9 mL)
prior to anion exchange desalting.
For anion exchange desalting of the deprotected
oligomer, the TEAR solution was loaded onto a Qiagen 500~
anion exchange cartridge (Qiagen Inc.) that was prewashed
with 50 mM TEAB (10 mL). After washing the loaded
cartridge with 50 mM TEAB (10 mL), the RNA was eluted with
2 M TEAB (10 mL) and dried down to a white powder.
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WO 99/50403 PCT/US99/06507
Inactive hammerhead ribozymes were synthesized by
substituting a U for G5 and a U for A14 (numbering from
Hertel, K. J., et al., 1992, Nucleic Acids Res., 20,
3252).
5 The average stepwise coupling yields were >98~
(Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684).
Hairpin ribozymes are synthesized in two parts and
annealed to reconstruct the active ribozyme (Chowrira and
Burke, 1992 Nucleic Acids Res., 20, 2835-2840). Ribozymes
10 are also synthesized from DNA templates using
bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck,
1989, Methods Enzymol. 180, 51).
Ribozymes are modified to enhance stability and/or
enhance catalytic activity by modification with nuclease
15 resistant groups, for example, 2'-amino, 2'-C-allyl, 2'
flouro, 2'-O-methyl, 2'-H, nucleotide base modifications
(for a review see Usman and Cedergren, 1992 TIBS 17, 34;
Usman et al., 1994 Nucleic Acids Symp. Ser. 31, 163;
Burgin et al., 1996 Biochemistry 6, 14090).
20 Ribozymes Were purified by gel electrophoresis using
general methods or are purified by high pressure liquid
chromatography (HPLC; See Stinchcomb et al., International
PCT Publication No. WO 95/23225, the totality of which is
hereby incorporated herein by reference) and are
25 resuspended in water.
The sequences of the ribozymes that are chemically
synthesized, useful in this study, are shown in Tables
III-X. Those in the art will recognize that these
sequences are representative only of many more such
sequences where the enzymatic portion of the ribozyme (all
but the binding arms) is altered to affect activity. For
example, stem-loop II sequence of hammerhead ribozymes can
be altered (substitution, deletion, and/or insertion) to
contain any sequences provided a minimum of two base-
paired stem structure can form. Similarly, stem-loop IV
CA 02324421 2000-09-26
WO 99/50403 PCTlUS99/06507
26
sequence of hairpin ribozymes, can be altered
(substitution, deletion, and/or insertion) to contain any
sequence, provided a minimum of two base-paired stem
structure can form. Preferably, no more than 200 bases
are inserted at these locations. The sequences listed in
Tables III-X may be formed of ribonucleotides or other
nucleotides or non-nucleotides. Such ribozymes (which have
enzymatic activity) are equivalent to the ribozymes
described specifically in the Tables.
Optimizing Ribozyme Activity
Catalytic activity of the ribozymes described in the
instant invention can be optimized as described by Draper
et al., supra. The details will not be repeated here, but
include altering the length of the ribozyme binding arms,
or chemically synthesizing ribozymes with modifications
(base, sugar and/or phosphate) that prevent their
degradation by serum ribonucleases and/or enhance their
enzymatic activity (see e.g., Eckstein et al.,
International Publication No. WO 92/07065; Perrault et
al., 1990 Nature 344, 565; Pieken et al., 1991 Science
253, 314; Usman and Cedergren, 1992 Trends in Biochem.
Sci. 17, 334; Usman et al., International Publication No.
WO 93/15187; and Rossi et al., International Publication
No. WO 91/03162; Sproat, US Patent No. 5,334,711; and
Burgin et al., supra all of these describe various
chemical modifications that can be made to the base,
phosphate and/or sugar moieties of enzymatic RNA
molecules). Modifications which enhance their efficacy in
cells, and removal of bases from stem loop structures to
shorten RNA synthesis times and reduce chemical
requirements are desired. (All these publications are
hereby incorporated by reference herein).
There are several examples in the art describing
sugar, base and phosphate modifications that can be
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
27
introduced into enzymatic nucleic acid molecules without
significantly effecting catalysis and with significant
enhancement in their nuclease stability and efficacy.
Ribozymes are modified to enhance stability and/or enhance
catalytic activity by modification with nuclease resistant
groups, for example, 2'-amino, 2'-C-allyl, 2'-flouro, 2'-
O-methyl, 2'-H, nucleotide base modifications (for a
review see Usman and Cedergren, 1992 TIBS 17, 34; Usman et
al., 1994 Nucleic Acids Symp. Ser. 31, 163: Burgin et al.,
1996 Biochemistry 35, 14090). Sugar modification of
enzymatic nucleic acid molecules have been extensively
described in the art (see Eckstein et al., International
Publication PCT No. WO 92/07065; Perrault et a1. Nature
1990, 394, 565-568; Pieken et a1. Science 1991, 253, 314-
317; Usman and Cedergren, Trends in Biochem. Sci. 1992,
17, 334-339; Usman et a1. International Publication PCT
No. WO 93/15187; Sproat, US Patent No. 5,334,711 and
Beigelman et al., 1995 J. Biol. Chem. 270, 25702; all of
the references are hereby incorporated in their totality
by reference herein). Such publications describe general
methods and strategies to determine the location of
incorporation of sugar, base and/or phosphate
modifications and the like into ribozymes without
inhibiting catalysis, and are incorporated by reference
herein. In view of such teachings, similar modifications
can be used as described herein to modify the nucleic acid
catalysts of the instant invention.
Nucleic acid catalysts having chemical modifications
which maintain or enhance enzymatic activity are provided.
Such nucleic acid is also generally more resistant to
nucleases than unmodified nucleic acid. Thus, in a cell
and/or in vivo the activity may not be significantly
lowered. As exemplified herein such ribozymes are useful
in a cell and/or in vivo even if activity over all is
reduced 10 fold (Burgin et al., 1996, Biochemistry, 35,
CA 02324421 2000-09-26
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28
14090) . Such ribozymes herein are said to "maintain" the
enzymatic activity on all RNA ribozyme.
Therapeutic ribozymes delivered exogenously must
optimally be stable within cells until translation of the
target RNA has been inhibited long enough to reduce the
levels of the undesirable protein. This period of time
varies between hours to days depending upon the disease
state. Clearly, ribozymes must be resistant to nucleases
in order to function as effective intracellular
therapeutic agents. Improvements in the chemical
synthesis of RNA (Wincott et al., 1995 Nucleic Acids Res.
23, 2677; incorporated by reference herein) have expanded
the ability to modify ribozymes by introducing nucleotide
modifications to enhance their nuclease stability as
described above.
By "nucleotide" as used herein is as recognized in
the art to include natural bases (standard), and modified
bases well known in the art. Such bases are generally
located at the 1' position of a sugar moiety. Nucleotide
generally comprise a base, sugar and a phosphate group.
The nucleotides can be unmodified or modified at the
sugar, phosphate and/or base moiety, (also referred to
interchangeably as nucleotide analogs, modified
nucleotides, non-natural nucleotides, non-standard
nucleotides and other; see for example, Usman and
McSwiggen, supra; Eckstein et al., International PCT
Publication No. WO 92/07065; Usman et al., International
PCT Publication No. WO 93/15187; all hereby incorporated
by reference herein). There are several examples of
modified nucleic acid bases known in the art and has
recently been summarized by Limbach et al., 1994, Nucleic
Acids Res. 22, 2183. Some of the non-limiting examples
of base modifications that can be introduced into
enzymatic nucleic acids without significantly effecting
their catalytic activity include, inosine, purine,
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29
pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2, 4,
6-trimethoxy benzene, 3-methyl uracil, dihydrouridine,
naphthyl, aminophenyl, 5-alkylcytidines (e.g., 5-
methylcytidine), 5-alkyluridines (e.g., ribothymidine), 5-
halouridine (e.g., 5-bromouridine) or 6-azapyrimidines or
6-alkylpyrimidines (e. g. 6-methyluridine) and others
(Burgin et al., 1996, Biochemistry, 35, 14090). By
"modified bases" in this aspect is meant nucleotide bases
other than adenine, guanine, cytosine and uracil at 1'
position or their equivalents; such bases may be used
within the catalytic core of the enzyme and/or in the
substrate-binding regions.
By "unmodified nucleoside" is meant one of the bases
adenine, cytosine, guanine, uracil joined to the 1' carbon
of b-D-ribo-furanose.
By "modified nucleoside" is meant any nucleotide base
which contains a modification in the chemical structure of
an unmodified nucleotide base, sugar and/or phosphate.
Various modifications to ribozyme structure can be
made to enhance the utility of ribozymes. Such
modifications will enhance shelf-life, half-life in vitro,
stability, and ease of introduction of such ribozymes to
the target site, e.g., to enhance penetration of cellular
membranes, and confer the ability to recognize and bind to
targeted cells.
Administration of Ribozymes
Sullivan et al., PCT WO 94/02595, describes the
general methods for delivery of enzymatic RNA molecules .
Ribozymes may be administered to cells by a variety of
methods known to those familiar to the art, including, but
not restricted to, encapsulation in liposomes, by
iontophoresis, or by incorporation into other vehicles,
such as hydrogels, cyclodextrins, biodegradable
nanocapsules, and bioadhesive microspheres. For some
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indications, ribozymes may be directly delivered ex vivo
to cells or tissues with or without the aforementioned
vehicles. Alternatively, the RNA/vehicle combination is
locally delivered by direct injection or by use of a
5 catheter, infusion pump or stent. Other routes of
delivery include, but are not limited to, intravascular,
intramuscular, subcutaneous or joint injection, aerosol
inhalation, oral (tablet or pill form), topical, systemic,
ocular, intraperitoneal and/or intrathecal delivery. More
10 detailed descriptions of ribozyme delivery and
administration are provided in Sullivan et al., supra and
Draper et al., PCT W093/23569 which have been incorporated
by reference herein.
The molecules of the instant invention can be used as
15 pharmaceutical agents. Pharmaceutical agents prevent,
inhibit the occurrence, or treat (alleviate a symptom to
some extent, preferably all of the symptoms) of a disease
state in a patient.
The negatively charged polynucleotides of the
20 invention can be administered (e. g., RNA, DNA or protein)
and introduced into a patient by any standard means, with
or without stabilizers, buffers, and the like, to form a
pharmaceutical composition. When it is desired to use a
liposome delivery mechanism, standard protocols for
25 formation of liposomes can be followed. The compositions
of the present invention may also be formulated and used
as tablets, capsules or elixirs for oral administration;
suppositories for rectal administration; sterile
solutions; suspensions for injectable administration; and
30 the like.
The present invention also includes pharmaceutically
acceptable formulations of the compounds described. These
formulations include salts of the above compounds, e.g.,
acid addition salts, for example, salts of hydrochloric,
hydrobromic, acetic acid, and benzene sulfonic acid.
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A pharmacological composition or formulation refers
to a composition or formulation in a form suitable for
administration, e.g., systemic administration, into a cell
or patient, preferably a human. Suitable forms, in part,
depend upon the use or the route of entry, for example
oral, transdermal, or by injection. Such forms should not
prevent the composition or formulation to reach a target
cell (i.e., a cell to which the negatively charged polymer
is desired to be delivered to). For example,
pharmacological compositions injected into the blood
stream should be soluble. Other factors are known in the
art, and include considerations such as toxicity and forms
which prevent the composition or formulation from exerting
its effect.
By "systemic administration" is meant in vivo
systemic absorption or accumulation of drugs in the blood
stream followed by distribution throughout the entire
body. Administration routes which lead to systemic
absorption include, without limitations: intravenous,
subcutaneous, intraperitoneal, inhalation, oral,
intrapulmonary and intramuscular. Each of these
administration routes expose the desired negatively
charged polymers, e.g., nucleic acids, to an accessible
diseased tissue. The rate of entry of a drug into the
circulation has been shown to be a function of molecular
weight or size. The use of a liposome or other drug
carrier comprising the compounds of the instant invention
can potentially localize the drug, for example, in certain
tissue types, such as the tissues of the reticular
endothelial system (RES). A liposome formulation which
can facilitate the association of drug with the surface of
cells, such as, lymphocytes and macrophages is also
useful. This approach may provide enhanced delivery of
the drug to target cells by taking advantage of the
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specificity of macrophage and lymphocyte immune
recognition of abnormal cells, such as the cancer cells.
The invention also features the use of the a
composition comprising surface-modified liposomes
containing poly (ethylene glycol) lipids (PEG-modified, or
long-circulating liposomes or stealth liposomes). These
formulations offer an method for increasing the
accumulation of drugs in target tissues. This class of
drug carriers resists opsonization and elimination by the
mononuclear phagocytic system (MPS or RES), thereby
enabling longer blood circulation times and enhanced
tissue exposure for the encapsulated drug (Lasic et a1.
Chem. Rev. 1995, 95, 2601-2627; Ishiwataet al., Chem.
Pharm. Bull. 2995, 43, 1005-1011). Such liposomes have
been shown to accumulate selectively in tumors, presumably
by extravasation and capture in the neovascularized target
tissues (Lasic et al., Science 1995, 267, 1275-1276; Oku
et a1.,1995, Biochim. Biophys. Acta, 1238, 86-90). The
long-circulating liposomes enhance the pharmacokinetics
and pharmacodynamics of DNA and RNA, particularly compared
to conventional cationic liposomes which are known to
accumulate in tissues of the MPS (Liu et al., J. Biol.
Chem. 1995, 42, 24864-24870; Choi et al., International
PCT Publication No. WO 96/10391; Ansell et al.,
International PCT Publication No. WO 96/10390; Holland et
al., International PCT Publication No. WO 96/10392; all of
these are incorporated by reference herein). Long-
circulating liposomes are also likely to protect drugs
from nuclease degradation to a greater extent compared to
cationic liposomes, based on their ability to avoid
accumulation in metabolically aggressive MPS tissues such
as the liver and spleen. All of these references are
incorporated by reference herein.
The present invention also includes compositions
prepared for storage or administration which include a
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pharmaceutically effective amount of the desired compounds
in a pharmaceutically acceptable carrier or diluent.
Acceptable carriers or diluents for therapeutic use are
well known in the pharmaceutical art, and are described,
for example, in Remington's Pharmaceutical Sciences, Mack
Publishing Co. (A. R. Gennaro edit. 1985) hereby
incorporated by reference herein. For example,
preservatives, stabilizers, dyes and flavoring agents may
be provided. Id. at 1949. These include sodium benzoate,
sorbic acid and esters of p-hydroxybenzoic acid. In
addition, antioxidants and suspending agents may be used.
Id.
A pharmaceutically effective dose is that dose
required to prevent, inhibit the occurrence, or treat
(alleviate a symptom to some extent, preferably all of the
symptoms) of a disease state. The pharmaceutically
effective dose depends on the type of disease, the
composition used, the route of administration, the type of
mammal being treated, the physical characteristics of the
specific mammal under consideration, concurrent
medication, and other factors which those skilled in the
medical arts will recognize. Generally, an amount between
0.1 mg/kg . and 100 mg/kg body weight/day of active
ingredients is administered dependent upon potency of the
negatively charged polymer.
Alternatively, the enzymatic nucleic acid molecules
of the instant invention can be expressed within cells
from eukaryotic promoters (e. g., Izant and Weintraub, 1985
Science 229, 345; McGarry and Lindquist, 1986 Proc. Natl.
Acad. Sci. USA 83, 399; Scanlon et al., 1991, Proc. Natl.
Acad. Sci. USA, 88, 10591-5; Kashani-Sabet et al., 1992
Antisense Res. Dev., 2, 3-15; Dropulic et al., 1992 J.
Virol, 66, 1432-41; Weerasinghe et al., 1991 J. Virol,
65, 5531-4; Ojwang et al., 1992 Proc. Natl. Acad. Sci.
USA 89, 10802-6; Chen et al., 1992 Nucleic Acids Res.,
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34
20, 4581-9~ Sarver et al., 1990 Science 247, 1222-1225;
Thompson et al., 1995 Nucleic Acids Res. 23, 2259; Good et
al., 1997, Gene Therapy, 9, 45; all of the references are
hereby incorporated in their totality by reference
herein). Those skilled in the art realize that any nucleic
acid can be expressed in eukaryotic cells from the
appropriate DNA/RNA vector. The activity of such nucleic
acids can be augmented by their release from the primary
transcript by a ribozyme (Draper et al., PCT WO 93/23569,
and Sullivan et al., PCT WO 94/02595 Ohkawa et al., 1992
Nucleic Acids Symp. Ser., 27, 15-6; Taira et al., 1991,
Nucleic Acids Res., 19, 5125-30; Ventura et al., 1993
Nucleic Acids Res., 21, 3249-55; Chowrira et al., 1994 J.
Biol. Chem. 269, 25856; all of the references are hereby
incorporated in their totality by reference herein).
In another aspect of the invention, enzymatic nucleic
acid molecules that cleave target molecules are expressed
from transcription units (see for example Couture et al.,
1996, TIG., 12, 510) inserted into DNA or RNA vectors. The
recombinant vectors are preferably DNA plasmids or viral
vectors. Ribozyme expressing viral vectors could be
constructed based on, but not limited to, adeno-associated
virus, retrovirus, adenovirus, or alphavirus. Preferably,
the recombinant vectors capable of expressing the
ribozymes are delivered as described above, and persist in
target cells. Alternatively, viral vectors may be used
that provide for transient expression of ribozymes. Such
vectors might be repeatedly administered as necessary.
Once expressed, the ribozymes cleave the target RNA. The
active ribozyme contains an enzymatic center or core
equivalent to those in the examples, and binding arms able
to bind target nucleic acid molecules such that cleavage
at the target site occurs. Other sequences may be present
which do not interfere with such cleavage. Delivery of
ribozyme expressing vectors could be systemic, such as by
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intravenous or intramuscular administration, by
administration to target cells ex-planted from the patient
followed by reintroduction into the patient, or by any
other means that would allow for introduction into the
5 desired target cell (for a review see Couture et al.,
1996, TIG., 12, 510).
In one aspect the invention features, an expression
vector comprising nucleic acid sequence encoding at least
one of the nucleic acid catalyst of the instant invention
10 is disclosed. The nucleic acid sequence encoding the
nucleic acid catalyst of the instant invention is operable
linked in a manner which allows expression of that nucleic
acid molecule.
In another aspect the invention features, the
15 expression vector comprises: a transcription initiation
region (e. g., eukaryotic pol I, II or III initiation
region): b) a transcription termination region (e. g.,
eukaryotic pol I, II or III termination region); c) a gene
encoding at least one of the nucleic acid catalyst of the
20 instant invention; and wherein said gene is operably
linked to said initiation region and said termination
region, in a manner which allows expression and/or
delivery of said nucleic acid molecule. The vector may
optionally include an. open reading frame (ORF) for a
25 protein operably linked on the 5' side or the 3'-side of
the gene encoding the nucleic acid catalyst of the
invention; and/or an intron (intervening sequences).
Transcription of the ribozyme sequences are driven
from a promoter for eukaryotic RNA polymerase I (pol I),
30 RNA polymerase II (pol II), or RNA polymerase III (pol
III). Transcripts from pol II or pol III promoters will
be expressed at high levels in all cells; the levels of a
given pol II promoter in a given cell type will depend on
the nature of the gene regulatory sequences (enhancers,
35 silencers, etc.) present nearby. Prokaryotic RNA
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36
polymerase promoters are also used, providing that the
prokaryotic RNA polymerase enzyme is expressed in the
appropriate cells (Elroy-Stein and Moss, 1990 Proc. Natl.
Acad. Sci. U S A, 87, 6743-7; Gao and Huang 1993 Nucleic
Acids Res., 21, 2867-72; Lieber et al., 1993 Methods
Enzymol., 217, 47-66~ Zhou et al., 1990 Mol. Cell.
Biol., 10, 4529-37). Several investigators have
demonstrated that ribozymes expressed from such promoters
can function in mammalian cells (e.g. Kashani-Sabet et
al., 1992 Antisense Res. Dev., 2, 3-15; Ojwang et al.,
1992 Proc. Natl. Acad. Sci. U S A, 89, 10802-6; Chen et
al., 1992 Nucleic Acids Res., 20, 4581-9; Yu et al., 1993
Proc. Natl. Acad. Sci. U S A, 90, 6340-4; L'Huillier et
al., 1992 EMBO J. 11, 4411-8; Lisziewicz et al., 1993
Proc. Natl. Acad. Sci. U. S. A., 90, 8000-4; Thompson et
al., 1995 Nucleic Acids Res. 23, 2259; Sullenger & Cech,
1993, Science, 262, 1566). More specifically,
transcription units such as the ones derived from genes
encoding U6 small nuclear (snRNA), transfer RNA (tRNA) and
adenovirus VA RNA are useful in generating high
concentrations of desired RNA molecules such as ribozymes
in cells (Thompson et al., supra; Couture and Stinchcomb,
1996, supra; Noonberg et al., 1994, Nucleic Acid Res., 22,
2830; Noonberg et al., US Patent No. 5,624,803; Good et
al., 1997, Gene Ther. 4, 45; Beigelman et al.,
International PCT Publication No. WO 96/18736; all of
these publications are incorporated by reference herein.
The above ribozyme transcription units can be incorporated
into a variety of vectors for introduction into mammalian
cells, including but not restricted to, plasmid DNA
vectors, viral DNA vectors (such as adenovirus or adeno-
associated virus vectors), or viral RNA vectors (such as
retroviral or alphavirus vectors) (for a review see
Couture and Stinchcomb, I996, supra).
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37
In yet another aspect the invention features an
expression vector comprising nucleic acid sequence
encoding at least one of the catalytic nucleic acid
molecule of the invention, in a manner which allows
expression of that nucleic acid molecule. The expression
vector comprises in one embodiment; a) a transcription
initiation region; b) a transcription termination region;
c) a gene encoding at least one said nucleic acid
molecules and wherein said gene is operably linked to said
initiation region and said termination region, in a manner
which allows expression and/or delivery of said nucleic
acid molecule. In another preferred embodiment the
expression vector comprises: a) a transcription initiation
regions b) a transcription termination region; c) an open
reading frame; d) a gene encoding at least one said
nucleic acid molecule, wherein said gene is operably
linked to the 3'-end of said open reading frame; and
wherein said gene is operably linked to said initiation
region, said open reading frame and said termination
region, in a manner which allows expression and/or
delivery of said nucleic acid molecule. In yet another
embodiment the expression vector comprises: a) a
transcription initiation region; b) a transcription
termination region; c) an intron~ d) a gene encoding at
least one said nucleic acid molecule; and wherein said
gene is operably linked to said initiation region, said
intron and said termination region, in a manner which
allows expression and/or delivery of said nucleic acid
molecule. In another embodiment, the expression vector
comprises: a) a transcription initiation region; b) a
transcription termination region; c) an intron; d) an
open reading frame; e) a gene encoding at least one said
nucleic acid molecule, wherein said gene is operably
linked to the 3'-end of said open reading framed and
wherein said gene is operably linked to said initiation
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region, said intron, said open reading frame and said
termination region, in a manner which allows expression
and/or delivery of said nucleic acid molecule.
Examples
The following are non-limiting examples showing the
selection, isolation, synthesis and activity of enzymatic
nucleic acids of the instant invention.
The following examples demonstrate the selection of
ribozymes that cleave Tie-2, integrin subunit b3, integrin
subunit a6, and aryl hydrocarbon nuclear transporter
(ARNT). The methods described herein represent a scheme
by which ribozymes may be derived that cleave other RNA
targets required for angiogenesis. Also provided is a
description of how such ribozymes may be delivered to
cells. The examples demonstrate that upon delivery, the
ribozymes inhibit cell proliferation in culture and
modulate gene expression in vivo. Moreover, significantly
reduced inhibition is observed if mutated ribozymes that
are catalytically inactive are applied to the cells.
Thus, inhibition requires the catalytic activity of the
ribozymes.
Example 1: Identification of Potential Ribozvme Cleavaae
Sites in TIE-2
The sequence of human Tie-2 was screened for
accessible sites using a computer folding algorithm.
Regions of the mRNA that did not form secondary folding
structures and contained potential hammerhead and/or
hairpin ribozyme cleavage sites were identified. The
sequences of these cleavage sites are shown in tables V
VI.
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Example 2: Selection of Ribozyme Cleavage Sites in Human_
mr~_~ Drtn
To test whether the sites predicted by the computer-
based RNA folding algorithm corresponded to accessible
sites in Tie-2 RNA, 20 hammerhead sites were selected for
analysis. Ribozyme target sites were chosen by analyzing
genomic sequences of Tie-2 (Ziegler et al., 1993, Oncogene
8 (3), 663-670 (Genbank sequence HUMTEKRPTK accession
number: M69238) and prioritizing the sites on the basis of
folding. Hammerhead ribozymes were designed that could
bind each target (see Figure 1) and were individually
analyzed by computer folding (Christoffersen et al., 1994
J. Mol. Struc. Theochem, 311, 273; Jaeger et al., 1989,
Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether
the ribozyme sequences fold into the appropriate secondary
structure. Those ribozymes with unfavorable
intramolecular interactions between the binding arms and
the catalytic core were eliminated from consideration. As
noted below, varying binding arm lengths can be chosen to
optimize activity. Generally, at least 5 bases on each
arm are able to bind to, or otherwise interact with, the
target RNA. An example of a ribozyme targeted to Tie-2 is
shown in figure 2.
Example 3: Chemical Synthesis and Purification of
Ribozymes for Efficient Cleavage of TIE-2 RNA
Ribozymes of the hammerhead or hairpin motif were
designed to anneal to various sites in the RNA message.
The binding arms are complementary to the target site
sequences described above. The ribozymes were chemically
synthesized. The method of synthesis used followed the
procedure for normal RNA synthesis as described in Usman
et al., (1987 J. Am. Chem. Soc., 109, 7845), Scaringe et
al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et
al., supra, and made use of common nucleic acid protecting
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and coupling groups, such as dimethoxytrityl at the 5'-
end, and phosphoramidites at the 3'-end. The average
stepwise coupling yields were >98$.
Inactive ribozymes were synthesized by substituting a
5 U for G5 and a U for A14 (numbering from Hertel et al.,
1992 Nucleic Acids Res., 20, 3252). Hairpin ribozymes
were synthesized in two parts and annealed to reconstruct
the active ribozyme (Chowrira and Burke, 1992 Nucleic
Acids Res., 20, 2835-2840). Ribozymes were also
10 synthesized from DNA templates using bacteriophage T7 RNA
polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol.
180, 51). Ribozymes were modified to enhance stability by
modification with nuclease resistant groups, for example,
2'-amino, 2'-C-allyl, 2'-flouro, 2'-O-methyl, 2'-H (for a
15 review see Usman and Cedergren, 1992 TIBS 17, 34).
Ribozymes were purified by gel electrophoresis using
general methods or were purified by high pressure liquid
chromatography (HPLC; See Wincott et al., supra; the
totality of which is hereby incorporated herein by
20 reference) and were resuspended in water. The sequences
of the chemically synthesized ribozymes used in this study
are shown below in Table V-VI.
Example 4: Ribozyme Cleavage of TIE-2 RNA Target in vitro
Ribozymes targeted to the human Tie-2 RNA are
25 designed and synthesized as described above. These
ribozymes can be tested for cleavage activity in vitro,
for example using the following procedure. The target
sequences and the nucleotide location within the Tie-2
mRNA are given in Table V.
30 Cleavage Reactions: Full-length or partially full-
length, internally-labeled target RNA for ribozyme
cleavage assay is prepared by in vitro transcription in
the presence of [a-32p] CTP, passed over a G 50 Sephadex
column by spin chromatography and used as substrate RNA
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41
without further purification. Alternately, substrates are
5'-32P-end labeled using T4 polynucleotide kinase enzyme.
Assays are performed by pre-warming a 2X concentration of
purified ribozyme in ribozyme cleavage buffer (50 mM Tris-
HC1, pH 7.5 at 37°C, 10 mM MgCl2) and the cleavage
reaction was initiated by adding the 2X ribozyme mix to an
equal volume of substrate RNA (maximum of 1-5 nM) that was
also pre-warmed in cleavage buffer. As an initial screen,
°
assays are carried out for 1 hour at 37 C using a final
concentration of either 40 nM or 1 mM ribozyme, i.e.,
ribozyme excess. The reaction is quenched by the addition
of an equal volume of 95$ formamide, 20 mM EDTA, 0.05$
bromophenol blue and 0.05$ xylene cyanol after which the
°
sample is heated to 95 C for 2 minutes, quick chilled and
loaded onto a denaturing polyacrylamide gel. Substrate
RNA and the specific RNA cleavage products generated by
ribozyme cleavage are visualized on an autoradiograph of
the gel. The percentage of cleavage is determined by
Phosphor Imager~ quantitation of bands representing the
intact substrate and the cleavage products.
Use of Ribozymes Targeting TIE-2
The rate of tumor growth is believed to be a function
of blood supplied and therefore a function of angiogenesis
(Rak, Supra; Blood & Zetter, 1990, Biochimica et
Biophysica Acta 1032, 89-118). Elevated levels of a
number of these angiogenic factors including Tie-2;
integrin subunit (i3; integrin subunit a6; and aryl
hydrocarbon nuclear transporter have been reported in a
number of cancers. Thus, inhibition of expression of
these angiogenic factors (for example using ribozymes)
would potentially reduce that rate of growth of these
tumors. The use of ribozymes would be desirable over such
therapies as chemotherapeutics since, chemotherapeutic
compounds such as doxorubicin because of its highly
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42
specific inhibition and reduction of the likelihood for
side effects. Ribozymes, with their catalytic activity
and increased site specificity (see above), are likely to
represent a potent and safe therapeutic molecule for the
treatment of cancer. Tumor angiogenesis and other
indications are discussed below.
Indications
1) Tumor angiogenesis: Angiogenesis has been shown
to be necessary for tumors to grow into pathological size
(Folkman, 1971, PNAS 76, 5217-5221; Wellstein & Czubayko,
1996, Breast Cancer Res and Treatment 38, 109-119). In
addition, it allows tumor cells to travel through the
circulatory system during metastasis. Increased levels of
gene expression of a number of angiogenic factors such as
vascular endothelial growth factor (VEGF) have been
reported in vascularized and edema-associated brain tumors
(Beckman et al., 1993 J. Clini. Invest. 91, 153). A more
direct demostration of the role of VEGF in tumor
angiogenesis was demonstrated by Jim Kim et al., 1993
Nature 362,841 wherein, monoclonal antibodies against VEGF
were successfully used to inhibit the growth of
rhabdomyosarcoma, glioblastoma multiforme cells in nude
mice. Similarly, expression of a dominant negative
mutated form of the flt-1 VEGF receptor inhibits
vascularization induced by human glioblastoma cells in
nude mice (Millauer et al., 1999, Nature 367, 576).
2) Ocular diseases: Neovascularization has been
shown to cause or exacerbate ocular diseases including but
not limited to, macular degeneration, neovascular
glaucoma, diabetic retinopathy, myopic degeneration, and
trachoma (Norrby, 1997, APMIS 105, 417-437). Aiello et
al., 1994 New Engl. J. Med. 331, 1480, showed that the
ocular fluid, of a majority of patients suffering from
diabetic retinopathy and other retinal disorders, contains
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43
a high concentration of VEGF. Miller et al., 1994 Am. J.
Pathol. 145, 574, reported elevated levels of VEGF mRNA in
patients suffering from retinal ischemia. These
observations support a direct role for VEGF in ocular
diseases. Other factors including those that stimulate
VEGF synthesis may also contribute to these indications.
3) Dermatological Disorders: Many indications have
been identified which may by angiogenesis dependent
including but not limited to psoriasis, verruca vulgaris,
angiofibroma of tuberous sclerosis, pot-wine stains,
Sturge Weber syndrome, Kippel-Trenaunay-Weber syndrome,
and Osler-Weber-Rendu syndrome (Norrby, supra).
Intradermal injection of the angiogenic factor b-FGF
demonstrated angiogenesis in nude mice (Weckbecker et al.,
1992, Angiogenesis: Key principles-Science-Technology
Medicine, ed R. Steiner) Detmar et al., 1999 J. Exp.
Med. 180, 1191 reported that VEGF and its receptors were
over-expressed in psoriatic skin and psoriatic dermal
microvessels, suggesting that VEGF plays a significant
role in psoriasis.
4) Rheumatoid arthritis: Immunohistochemistry and
in situ hybridization studies on tissues from the joints
of patients suffering from rheumatoid arthritis show an
increased level of VEGF and its receptors (Fava et al.,
1994 J. Exp. Med. 180, 341). Additionally, Koch et al.,
1994 J. Immunol. 152, 4149, found that VEGF-specific
antibodies were able to significantly reduce the mitogenic
activity of synovial tissues from patients suffering from
rheumatoid arthritis. These observations support a direct
role for VEGF in rheumatoid arthritis. Other angiogenic
factors including those of the present invention may also
be involved in arthritis.
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Animal Models
There are several animal models in which the anti-
angiogenesis effect of nucleic acids of the present
invention, such as ribozymes, directed against ARNT RNAs
can be tested. Typically a corneal model has been used
to study angiogenesis in rat and rabbit since recruitment
of vessels can easily be followed in this normally
avascular tissue (Pandey et al., 1995 Science 268: 567-
569). In these models, a small Teflon or Hydron disk
pretreated with an angiogenic compound is inserted into a
pocket surgically created in the cornea. Angiogenesis is
monitored 3 to 5 days later. Ribozymes directed against
ARNT, Tie-2 or integrin subunit RNAs would be delivered in
the disk as well, or dropwise to the eye over the time
course of the experiment. In another eye model, hypoxia
has been shown to cause both increased expression of VEGF
and neovascularization in the retina (Pierce et al., 1995
Proc. Natl. Acad. Sci. USA. 92: 905-909; Shweiki et al.,
1992 J. Clin. Invest. 91: 2235-2243).
Another animal model that addresses
neovascularization involves Matrigel, an extract of
basement membrane that becomes a solid gel when injected
subcutaneously (Passaniti et al., 1992 Lab. Invest. 67:
519-528). When the Matrigel is supplemented with
angiogenesis factors, vessels grow into the Matrigel over
a period of 3 to 5 days and angiogenesis can be assessed.
Again, ribozymes directed against ARNT, Tie-2 or integrin
subunit RNAs would be delivered in the Matrigel.
Several animal models exist for screening of anti
angiogenic agents. These include corneal vessel formation
following corneal injury (Burger et al., 1985 Cornea 4:
35-41; Lepri, et al., 1994 J. Ocular Pharmacol. 10: 273
280; Ormerod et al., 1990 Am. J. Pathol. 137: 1243-1252)
or intracorneal growth factor implant (Grant et al., 1993
Diabetologia 36: 282-291; Pandey et a1. 1995 supra;
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Zieche et al., 1992 Lab. Invest. 67: 711-715), vessel
growth into Matrigel matrix containing growth factors
(Passaniti et al., 1992 supra), female reproductive organ
neovascularization following hormonal manipulation
5 (Shweiki et al., 1993 Clin. Invest. 91: 2235-2243),
several models involving inhibition of tumor growth in
highly vascularized solid tumors (0'Reilly et al., 1994
Cell 79: 315-328; Senger et al., 1993 Cancer and Metas.
Rev. 12: 303-329; Takahasi et al., 1994 Cancer Res. 54:
10 4233-4237; Kim et al., 1993 supra), and transient hypoxia-
induced neovascularization in the mouse retina (Pierce et
al., 1995 Proc. Natl. Acad. Sci. USA. 92: 905-909).
The cornea model, described in Pandey et al. supra,
is the most common and well characterized anti-angiogenic
15 agent efficacy screening model. This model involves an
avascular tissue into which vessels are recruited by a
stimulating agent (growth factor, thermal or alkalai burn,
endotoxin). The corneal model would utilize the
intrastromal corneal implantation of a Teflon pellet
20 soaked in a angiogenic compound-Hydron solution to recruit
blood vessels toward the pellet which can be quantitated
using standard microscopic and image analysis techniques.
To evaluate their anti-angiogenic efficacy, ribozymes are
applied topically to the eye or bound within Hydron on the
25 Teflon pellet itself. This avascular cornea as well as
the Matrigel (see below) provide for low background
assays. While the corneal model has been performed
extensively in the rabbit, studies in the rat have also
been conducted.
30 The mouse model (Passaniti et al., supra) is a non-
tissue model which utilizes Matrigel, an extract of
basement membrane (Kleinman et al., 1986) or Millipore~
filter disk, which can be impregnated with growth factors
and anti-angiogenic agents in a liquid form prior to
35 injection. Upon subcutaneous administration at body
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46
temperature, the Matrigel or Millipore~ filter disk forms
a solid implant. An angiogenic compound would be embedded
in the Matrigel or Millipore~ filter disk which would be
used to recruit vessels within the matrix of the Matrigel
or Millipore~ filter disk that can be processed
histologically for endothelial cell specific vWF (factor
VIII antigen) immunohistochemistry, Trichrome-Masson
stain, or hemoglobin content. Like the cornea, the
Matrigel or Millipore~ filter disk are avascular; however,
it is not tissue. In the Matrigel or Millipore~ filter
disk model, ribozymes are administered within the matrix
of the Matrigel or Millipore~ filter disk to test their
anti-angiogenic efficacy. Thus, delivery issues in this
model, as with delivery of ribozymes by Hydron- coated
Teflon pellets in the rat cornea model, may be less
problematic due to the homogeneous presence of the
ribozyme within the respective matrix.
These models offer a distinct advantage over several
other angiogenic models listed previously. The ability to
use VEGF as a pro-angiogenic stimulus in both models is
highly desirable since ribozymes will target only VEGFr
RNA. In other words, the involvement of other non-
specific types of stimuli in the cornea and Matrigel
models is not advantageous from the standpoint of
understanding the pharmacologic mechanism by which the
anti-VEGFr RNA ribozymes produce their effects. In
addition, the models will allow for testing the
specificity of the anti-VEGFr RNA ribozymes by using
either a- or bFGF as a pro-angiogenic factor. Vessel
recruitment using FGF should not be affected in either
model by anti-VEGFr RNA ribozymes. Other models of
angiogenesis including vessel formation in the female
reproductive system using hormonal manipulation (Shweiki
et al., 1993 supra); a variety of vascular solid tumor
models which involve indirect correltations with
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angiogenesis (O'Reilly et al., 1994 supra; Senger et al.,
1993 supra; Takahasi et al., 1994 supra; Kim et al., 1993
supra); and retinal neovascularization following transient
hypoxia (Pierce et al., 1995 supra) were not selected for
efficacy screening due to their non-specific nature,
although there is a correlation between VEGF and
angiogenesis in these models.
Other model systems to study tumor angiogenesis is
reviewed by Folkman, 1985 Adv. Cancer. Res.. 43, 175.
Use of murine models
For a typical systemic study involving 10 mice (20 g
each) per dose group, 5 doses (1, 3, 10, 30 and 100 mg/kg
daily over 14 days continuous administration),
approximately 400 mg of ribozyme, formulated in saline
would be used. A similar study in young adult rats (200
g) would require over 4 g. Parallel pharmacokinetic
studies may involve the use of similar quantities of
ribozymes further justifying the use of murine models.
Ribozymes and Lewis lung carcinoma and B-16 melanoma
murine models
Identifying a common animal model for systemic
efficacy testing of ribozymes is an efficient way of
screening ribozymes for systemic efficacy.
The Lewis lung carcinoma and B-16 murine melanoma
models are well accepted models of primary and metastatic
cancer and are used for initial screening of anti-cancer.
These murine models are not dependent upon the use of
immunodeficient mice, are relatively inexpensive, and
minimize housing concerns. Both the Lewis lung and B-16
melanoma models involve subcutaneous implantation of
approximately 10' tumor cells from metastatically
aggressive tumor cell lines (Lewis lung lines 3LL or D122,
LLc-LN7; B-16-BL6 melanoma) in C57BL/6J mice.
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Alternatively, the Lewis lung model can be produced by the
surgical implantation of tumor spheres (approximately 0.8
mm in diameter). Metastasis also may be modeled by
injecting the tumor cells directly i.v.. In the Lewis
lung model, microscopic metastases can be observed
approximately 14 days following implantation with
quantifiable macroscopic metastatic tumors developing
within 21-25 days. The B-16 melanoma exhibits a similar
time course with tumor neovascularization beginning 4 days
following implantation. Since both primary and metastatic
tumors exist in these models after 21-25 days in the same
animal, multiple measurements can be taken as indices of
efficacy. Primary tumor volume and growth latency as well
as the number of micro- and macroscopic metastatic lung
foci or number of animals exhibiting metastases can be
quantitated. The percent increase in lifespan can also be
measured. Thus, these models would provide suitable
primary efficacy assays for screening systemically
administered ribozymes/ribozyme formulations.
In the Lewis lung and B-16 melanoma models, systemic
pharmacotherapy with a wide variety of agents usually
begins 1-7 days following tumor implantation/inoculation
with either continuous or multiple administration
regimens. Concurrent pharmacokinetic studies can be
performed to determine whether sufficient tissue levels of
ribozymes can be achieved for pharmacodynamic effect to be
expected. Furthermore, primary tumors and secondary lung
metastases can be removed and subjected to a variety of in
vitro studies (i.e, target RNA reduction).
Delivery of ribozymes and ribozyme formulations in the
Lewis lung model
Several ribozyme formulations, including cationic
lipid complexes which may be useful for inflammatory
diseases (e. g. DIMRIE/DOPE, etc.) and RES evading
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liposomes which may be used to enhance vascular exposure
of the ribozymes, are of interest in cancer models due to
their presumed biodistribution to the lung. Thus, liposome
formulations can be used for delivering ribozymes to sites
of pathology linked to an angiogenic response.
Diagnostic uses
Ribozymes of this invention may be used as diagnostic
tools to examine genetic drift and mutations within
diseased cells or to detect the presence of Tie-2;
integrin subunit ~i3; integrin subunit a6; and/or aryl
hydrocarbon nuclear transporter RNA in a cell. The close
relationship between ribozyme activity and the structure
of the target RNA allows the detection of mutations in any
region of the molecule which alters the base-pairing and
three-dimensional structure of the target RNA. By using
multiple ribozymes described in this invention, one may
map nucleotide changes which are important to RNA
structure and function in vitro, as well as in cells and
tissues. Cleavage of target RNAs with ribozymes may be
used to inhibit gene expression and define the role
(essentially) of specified gene products in the
progression of disease. In this manner, other genetic
targets may be defined as important mediators of the
disease. These experiments will lead to better treatment
of the disease progression by affording the possibility of
combinational therapies (e. g., multiple ribozymes targeted
to different genes, ribozymes coupled with known small
molecule inhibitors, or intermittent treatment with
combinations of ribozymes and/or other chemical or
biological molecules). Other in vitro uses of ribozymes
of this invention are well known in the art, and include
detection of the presence of RNAs associated with Tie-2;
integrin subunit (33; integrin subunit a6; and/or aryl
hydrocarbon nuclear transporter related condition. Such
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RNA is detected by determining the presence of a cleavage
product after treatment with a ribozyme using standard
methodology.
In a specific example, ribozymes which can cleave
5 only wild-type or mutant forms of the target RNA are used
for the assay. The first ribozyme is used to identify
wild-type RNA present in the sample and the second
ribozyme will be used to identify mutant RNA in the
sample. As reaction controls, synthetic substrates of
10 both wild-type and mutant RNA will be cleaved by both
ribozymes to demonstrate the relative ribozyme
efficiencies in the reactions and the absence of cleavage
of the "non-targeted" RNA species. The cleavage products
from the synthetic substrates will also serve to generate
15 size markers for the analysis of wild-type and mutant RNAs
in the sample population. Thus each analysis will
require two ribozymes, two substrates and one unknown
sample which will be combined into six reactions. The
presence of cleavage products will be determined using an
20 RNAse protection assay so that full-length and cleavage
fragments of each RNA can be analyzed in one lane of a
polyacrylamide gel. It is not absolutely required to
quantify the results to gain insight into the expression
of mutant RNAs and putative risk of the desired phenotypic
25 changes in target cells. The expression of mRNA whose
protein product is implicated in the development of the
phenotype (i.e., Tie-2; integrin subunit (33; integrin
subunit a6; ARNT) is adequate to establish risk. If
probes of comparable specific activity are used for both
30 transcripts, then a qualitative comparison of RNA levels
will be adequate and will decrease the cost of the initial
diagnosis. Higher mutant form to wild-type ratios will be
correlated with higher risk whether RNA levels are
compared qualitatively or quantitatively.
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Additional Uses
Potential usefulness of sequence-specific enzymatic
nucleic acid molecules of the instant invention might have
many of the same applications for the study of RNA that
DNA restriction endonucleases have for the study of DNA
(Nathans et al., 1975 Ann. Rev. Biochem. 44:273). For
example, the pattern of restriction fragments could be
used to establish sequence relationships between two
related RNAs, and large RNAs could be specifically cleaved
to fragments of a size more useful for study. The ability
to engineer sequence specificity of the ribozyme is ideal
for cleavage of RNAs of unknown sequence.
Other embodiments are within the following claims.
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TABLE I
Characteristics of naturally occurring ribozymes
Group I Introns
~ Size: 150 to >1000 nucleotides.
~ Requires a U in the target sequence immediately
5' of the cleavage site.
~ Binds 4-6 nucleotides at the 5'-side of the
cleavage site.
~ Reaction mechanism: attack by the 3'-OH of
guanosine to generate cleavage products with 3'-OH and 5'
guanosine.
~ Additional protein cofactors required in some
cases to help folding and maintainance of the active
structure.
~ Over 300 known members of this class . Found as
an intervening sequence in Tetrahymena thermophila rRNA,
fungal mitochondria, chloroplasts, phage T4, blue-green
algae, and others.
~ Major structural features largely established
through phylogenetic comparisons, mutagenesis, and
biochemical studies [1,2] .
~ Complete kinetic framework established for one
ribozyme [3, 9, 5~ s] .
Michel, Francois; Westhof, Eric. Slippery substrates. Nat.
Struct. Biol. (1994), 1(1), 5-7.
Lisacek, Frederique; Diaz, Yolande; Michel, Francois. Automatic
identification of group I intron cores in genomic DNA sequences. J.
Mol. Biol. (1994), 235(9), 1206-17.
Herschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by
the Tetrahymena thermophila ribozyme. 1. Kinetic description of the
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53
~ Studies of ribozyme folding and substrate
docking underway ['-, 8, 9] .
reaction of an RNA substrate complementary to the active site.
Biochemistry (1990), 29(44), 10159-71.
°- Herschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by
the Tetrahymena thermophila ribozyme. 2. Kinetic description of the
reaction of an RNA substrate that forms a mismatch at the active site.
Biochemistry (1990), 29(44), 10172-80.
Knitt, Deborah S.: Herschlag, Daniel. pH Dependencies of the
Tetrahymena Ribozyme Reveal an Unconventional Origin of an Apparent
pKa. Biochemistry (1996), 35(5), 1560-70.
Bevilacqua, Philip C.~ Sugimoto, Naoki; Turner, Douglas H.. A
mechanistic framework for the second step of splicing catalyzed by the
Tetrahymena ribozyme. Biochemistry (1996), 35(2), 648-58.
'- Li, Yi; Bevilacqua, Philip C.; Mathews, David; Turner, Douglas
H.. Thermodynamic and activation parameters for binding of a pyrene-
labeled substrate by the Tetrahymena ribozyme: docking is not
diffusion-controlled and is driven by a favorable entropy change.
Biochemistry (1995), 34(44), 14394-9.
Banerjee, Aloke Raj; Turner, Douglas H.. The time dependence of
chemical modification reveals slow steps in the folding of a group I
ribozyme. Biochemistry (1995), 34(19), 6504-12.
Zarrinkar, Patrick P.; Williamson, James R.. The P9.1-P9.2
peripheral extension helps guide folding of the Tetrahymena ribozyme.
Nucleic Acids Res. (1996), 24(5), 854-8.
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~ Chemical modification investigation of important
residues well established [lo, ii] .
~ The small (4-6 nt) binding site may make this
ribozyme too non-specific for targeted RNA cleavage,
however, the Tetrahymena group I intron has been used to
repair a "defective" ~i-galactosidase message by the
ligation of new (3-galactosidase sequences onto the
defective message [12] .
RNAse P RNA (M1 RNA)
~ Size: 290 to 400 nucleotides.
~ RNA portion of a ubiquitous ribonucleoprotein
enzyme.
~ Cleaves tRNA precursors to form mature tRNA [
~ Reaction mechanism: possible attack by M2+-OH to
generate cleavage products with 3'-OH and 5'-phosphate.
to Strobel, Scott A.: Cech, Thomas R.. Minor groove recognition of
the conserved G.cntdot.U pair at the Tetrahymena ribozyme reaction
site. Science (Washington, D. C.) (1995), 267(5198), 675-9.
11 Strobel, Scott A.; Cech, Thomas R.. Exocyclic Amine of the
Conserved G.cntdot.U Pair at the Cleavage Site of the Tetrahymena
Ribozyme Contributes to 5'-Splice Site Selection and Transition State
Stabilization. Biochemistry (1996), 35(4), 1201-11.
i2 Sullenger, Bruce A.; Cech, Thomas R.. Ribozyme-mediated repair
of defective mRNA by targeted trans-splicing. Nature (London) (1994),
371(6498), 619-22.
Robertson, H.D.; Altman, S.~ Smith, J.D. J. Biol. Chem., 247,
5243-5251 (1972).
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~ RNAse P is found throughout the prokaryotes and
eukaryotes. The RNA subunit has been sequenced from
bacteria, yeast, rodents, and primates.
~ Recruitment of endogenous RNAse P for
5 therapeutic applications is possible through hybridization
of an External Guide Sequence (EGS) to the target RNA
~19 15~
i
~ Important phosphate and 2' OH contacts recently
identified [ls,1']
10 Group II Introns
Size: >1000 nucleotides.
~ Trans cleavage of target RNAs recently
demonstrated [18 ls] .
1' Forster, Anthony C.; Altman, Sidney. External guide sequences
for an RNA enzyme. Science (Washington, D. C., 1883-) (1990),
249(4970), 783-6. -
is yuan, Y.; Hwang, E. S.; Altman, S. Targeted cleavage of mRNA by
human RNase P. Proc. Natl. Acad. Sci. USA (1992) 89, 8006-10.
is Harris, Michael E.; Pace, Norman R.. Identification of
phosphates involved in catalysis by the ribozyme RNase P RNA. RNA
(1995), 1(2), 210-18.
1' Pan, Tao; Loria, Andrew; Zhong, Kun. Probing of tertiary
interactions in RNA: 2'-hydroxyl-base contacts between the RNase P RNA
and pre-tRNA. Proc. Natl. Acad. Sci. U. S. A. (1995), 92(26), 12510-
19.
ie pyle, Anna Marie; Green, Justin B.. Building a Kinetic Framework
for Group II Intron Ribozyme Activity: Quantitation of Interdomain
Binding and Reaction Rate. Biochemistry (1994), 33(9), 2716-25.
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~ Sequence requirements not fully determined.
~ Reaction mechanism: 2'-OH of an internal
adenosine generates cleavage products with 3'-OH and a
"lariat" RNA containing a 3'-5' and a 2'-5' branch point.
~ Only natural ribozyme with demonstrated
participation in DNA cleavage [io~21] in addition to RNA
cleavage and ligation.
~ Major structural features largely established
through phylogenetic comparisons [2z].
~ Important 2' OH contacts beginning to be
identified [?3]
'-s Michels, William J. Jr.; Pyle, Anna Marie. Conversion of a Group
II Intron into a New Multiple-Turnover Ribozyme that Selectively
Cleaves Oligonucleotides: Elucidation of Reaction Mechanism and
Structure/Function Relationships. Biochemistry (1995), 39(9), 2965-77.
Zimmerly, Steven; Guo, Huatao; Eskes, Robert: Yang, Jian
Perlman, Philip S.~ Lambowitz, Alan M.. A group II intron RNA is a
catalytic component of a DNA endonuclease involved in intron mobility.
Cell (Cambridge, Mass.) (1995), 83(4), 529-38.
Zi Griffin, Edmund A., Jr.; Qin, Zhifeng; Michels, Williams J.,
Jr.; Pyle, Anna Marie. Group II intron ribozymes that cleave DNA and
RNA linkages with similar efficiency, and lack contacts with substrate
2'-hydroxyl groups. Chem. Biol. (1995), 2(11), 761-70.
Zz Michel, Francois~ Ferat, Jean Luc. Structure and activities of
group II introns. Annu. Rev. Biochem. (1995), 64, 935-61.
z3 Abramovitz, Dana L.; Friedman, Richard A.; Pyle, Anna Marie.
Catalytic role of 2'-hydroxyl groups within a group II intron active
site. Science (Washington, D. C.) (1996), 271(5254), 1410-13.
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~ Kinetic framework under development
Neurospora VS RNA
~ Size: 144 nucleotides.
~ Trans cleavage of hairpin target RNAs recently
demonstrated [25] .
~ Sequence requirements not fully determined.
~ Reaction mechanism: attack by 2'-OH 5' to the
scissile bond to generate cleavage products with 2',3'-
cyclic phosphate and 5'-OH ends.
~ Binding sites and structural requirements not
fully determined.
~ Only 1 known member of this class. Found in
Neurospora VS RNA.
Hammerhead Ribozyme
(see text for references)
~ Size: ~13 to 90 nucleotides.
~ Requires the target sequence UH immediately 5'
of the cleavage site.
~ Binds a variable number nucleotides on both
sides of the cleavage site.
~ Reaction mechanism: attack by 2'-OH 5' to the
scissile bond to generate cleavage products with 2',3'-
cyclic phosphate and 5'-OH ends.
24 Daniels, Danette L.; Michels, William J., Jr.; Pyle, Anna Marie.
Two competing pathways for self-splicing by group II introns: a
quantitative analysis of in vitro reaction rates and products. J. Mol.
Biol. (1996), 256(1), 31-99.
zs Guo, Hans C. T.: Collins, Richard A.. Efficient trans-cleavage
of a stem-loop RNA substrate by a ribozyme derived from Neurospora VS
RNA. EMBO J. (1995), 14(2), 368-76.
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~ 14 known members of this class. Found in a
number of plant pathogens (virusoids) that use RNA as the
infectious agent.
~ Essential structural features largely defined,
including 2 crystal structures [26, 27]
~ Minimal ligation activity demonstrated (for
engineering through in vitro selection) [2g]
~ Complete kinetic framework established for two
or more ribozymes [29] .
~ Chemical modification investigation of important
residues well established [30].
Hairpin Ribozyme
~ Size: ~50 nucleotides.
zs Scott, W.G., Finch, J.T., Aaron,K. The crystal structure of an
all RNA hammerhead ribozyme:Aproposed mechanism for RNA catalytic
cleavage. Cell, (1995), 81, 991-1002.
2' McKay, Structure and function of the hammerhead ribozyme: an
unfinished story. RNA, (1996), 2, 395-403.
?8 Long, D., Uhlenbeck, 0., Hertel, K. Ligation with hammerhead
ribozymes. US Patent No. 5,633,133.
?9 Hertel, K.J., Herschlag, D., Uhlenbeck, 0. A kinetic and
thermodynamic framework for the hammerhead ribozyme reaction.
Biochemistry, (1994) 33, 3374-3385.Beigelman, L., et al., Chemical
modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270,
25702-25708.
3° Beigelman, L:, et al., Chemical modifications of hammerhead
ribozymes. J. Biol. Chem., (1995) 270, 25702-25708.
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~ Requires the target sequence GUC immediately 3'
of the cleavage site.
~ Binds 4-6 nucleotides at the 5'-side of the
cleavage site and a variable number to the 3' -side of the
cleavage site.
~ Reaction mechanism: attack by 2'-OH 5' to the
scissile bond to generate cleavage products with 2',3'-
cyclic phosphate and 5'-OH ends.
~ 3 known members of this class. Found in three
plant pathogen (satellite RNAs of the tobacco ringspot
virus, arabis mosaic virus and chicory yellow mottle
virus) which uses RNA as the infectious agent.
~ Essential structural features largely defined
31 32 33 34
f-: ; ,-J
31 Hampel, Arnold; Tritz, Richard; Hicks, Margaret; Cruz, Phillip.
'Hairpin' catalytic RNA model: evidence for helixes and sequence
requirement for substrate RNA. Nucleic Acids Res. (1990), 18(2), 299-
304.
3z Chowrira, Bharat M.; Berzal-Herranz, Alfredo; Burke, John M..
Novel guanosine requirement for catalysis by the hairpin ribozyme.
Nature (London) (1991), 354(6351), 320-2.
33 gerzal-Herranz, Alfredo; Joseph, Simpson; Chowrira, Bharat M.:
Butcher, Samuel E.; Burke, John M.. Essential nucleotide sequences and
secondary structure elements of the hairpin ribozyme. EMBO J. (1993),
12(6), 2567-73.
39 Joseph, Simpson; Berzal-Herranz, Alfredo; Chowrira, Bharat M.;
Butcher, Samuel E.. Substrate selection rules for the hairpin ribozyme
determined by in vitro selection, mutation, and analysis of mismatched
substrates. Genes Dev. (1993), 7(1), 130-8.
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~ Ligation activity (in addition to cleavage
activity) makes ribozyme amenable to engineering through
in vitro selection [3s]
~ Complete kinetic framework established for one
5 ribozyme [36] .
~ Chemical modification investigation of important
residues begun [3'~ 3e~ .
Hepatitis Delta Virus (HDV) Ribozyme
~ Size: ~60 nucleotides.
10 ~ Trans cleavage of target RNAs demonstrated [39].
as Berzal-Herranz, Alfredo; Joseph, Simpson; Burke, John M.. In
vitro selection of active hairpin ribozymes by sequential RNA-
catalyzed cleavage and ligation reactions. Genes Dev. (1992), 6(1),
129-34.
3s Hegg, Lisa A.; Fedor, Martha J.. Kinetics and Thermodynamics of
Intermolecular Catalysis by Hairpin Ribozymes. Biochemistry (1995),
34(48), 15813-28.
3' Grasby, Jane A.; Mersmann, Karin; Singh, Mohinder; Gait, Michael
J.. Purine Functional Groups in Essential Residues of the Hairpin
Ribozyme Required for Catalytic Cleavage of RNA. Biochemistry (1995),
39(12), 4068-76.
3a Schmidt, Sabine; Beigelman, Leonid; Karpeisky, Alexander; Usman,
Nassim; Sorensen, Ulrik S.; Gait, Michael J.. Base and sugar
requirements for RNA cleavage of essential nucleoside residues in
internal loop B of the hairpin ribozyme: implications for secondary
structure. Nucleic Acids Res. (1996), 24(9), 573-B1.
39 Perrotta, Anne T.; Been, Michael D.. Cleavage of
oligoribonucleotides by a ribozyme derived from the hepatitis .delta.
virus RNA sequence. Biochemistry (1992), 31(1), 16-21.
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~ Binding sites and structural requirements not
fully determined, although no sequences 5' of cleavage
site are required. Folded ribozyme contains a pseudoknot
structure [40] .
~ Reaction mechanism: attack by 2'-OH 5' to the
scissile bond to generate cleavage products with 2',3'-
cyclic phosphate and 5'-OH ends.
~ Only 2 known members of this class. Found in
human HDV.
~ Circular form of HDV is active and shows
increased nuclease stability [9i]
'-° Perrotta, Anne T.: Been, Michael D.. A pseudoknot-like structure
required for efficient self-cleavage of hepatitis delta virus RNA.
Nature (London) (1991), 350(6317), 934-6.
41 puttaraju, M.; Perrotta, Anne T.; Been, Michael D.. A circular
trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res.
(1993), 21(18), 4253-8.
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Table II: 2.5 umol RNA Synthesis Cycle
Reagent Equivalents Amount Time*
Phosphoramidites 6.5 163 uL 2.5
S-Ethyl Tetrazole 23.8 238 uL 2.5
Acetic Anhydride 100 233 uL 5 sec
N-Methyl Imidazole 186 233 uL 5 sec
TCA 83.2 1.73 mL 21 sec
Iodine 8.0 1.18 mL 45 sec
Acetonitrile NA 6.67 mL NA
* Wait time does not include contact time during delivery.
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TABLE III: HAMMERHEAD RIBOZYME AND SITE SEQUENCES FOR ARNT
Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
AGUGGGAG CUGAUGAG X 1 UGGCGGCUC 394
CGAA
AGCCGCCA CUCCCACU
5 13 CCCAGUGG CUGAUGAG X 2 CGGCUCCUC 395
CGAA
AGGAGCCG CCACUGGG
49 UGGCCGCA CUGAUGAG X 3 GGUGGCAUC 396
CGAA
AUGCCACC UGCGGCCA
69 GUUGGCAG CUGAUGAG X 4 CGGCGACUA 397
CGAA
10 AGUCGCCG CUGCCAAC
91 GUACAUCU CUGAUGAG X 5 AAUGACAUC 398
CGAA
AUGUCAUU AGAUGUAC
98 AGUGAUGG CUGAUGAG X 6 UCAGAUGUA 399
CGAA
ACAUCUGA CCAUCACU
103 GACCCAGU CUGAUGAG X 7 UGUACCAUC 400
CGAA
AUGGUACA ACUGGGUC
111 AAUGGCUG CUGAUGAG X 8 CACUGGGUC 901
CGAA
ACCCAGUG CAGCCAUU
119 CCAGAGGC CUGAUGAG X 9 CCAGCCAUU 402
CGAA
AUGGCUGG GCCUCUGG
124 AGUUUCCA CUGAUGAG X 10 CAUUGCCUC 403
CGAA
AGGCAAUG UGGAAACU
133 CAGGUCCA CUGAUGAG X 11 UGGAAACUC 404
CGAA
AGUUUCCA UGGACCUG
146 CCACCUUG CUGAUGAG X 12 CCUGGAAUU 405
CGAA
AUUCCAGG CAAGGUGG
147 UCCACCUU CUGAUGAG X 13 CUGGAAUUC 406
CGAA
AAUUCCAG AAGGUGGA
169 CUCUGGAC CUGAUGAG X 14 GGAGCCAUU 907
CGAA
AUGGCUCC GUCCAGAG
167 GCCCUCUG CUGAUGAG X 15 GCCAUUGUC 408
CGAA
ACAAUGGC CAGAGGGC
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
177 CCGCUUAA CUGAUGAG X 16 AGAGGGCUA 409
CGAA
AGCCCUCU UUAAGCGG
179 CGCCGCUU CUGAUGAG X 17 AGGGCUAUU 410
CGAA
AUAGCCCU AAGCGGCG
180 UCGCCGCU CUGAUGAG X 18 GGGCUAUUA 911
CGAA
AAUAGCCC AGCGGCGA
201 AUCAUCAA CUGAUGAG X 19 GGCUGGAUU 912
CGAA
AUCCAGCC UUGAUGAU
202 CAUCAUCA CUGAUGAG X 20 GCUGGAUUU 413
CGAA
AAUCCAGC UGAUGAUG
203 UCAUCAUC CUGAUGAG X 21 CUGGAUUUU 419
CGAA
AAAUCCAG GAUGAUGA
228 CAAAAAUU CUGAUGAG X 22 GGAACAGUA 415
CGAA
ACUGUUCC AAUUUUUG
232 ACCUCAAA CUGAUGAG X 23 CAGUAAAUU 916
CGAA
AUUUACUG UUUGAGGU
233 CACCUCAA CUGAUGAG X 29 AGUAAAUUU 917
CGAA
2 AAUUUACU UUGAGGUG
O
234 ACACCUCA CUGAUGAG X 25 GUAAAUUUU 418
CGAA
AAAUUUAC UGAGGUGU
235 CACACCUC CUGAUGAG X 26 UAAAUUUUU 419
CGAA
AAAAUUUA GAGGUGUG
252 AGACAUCU CUGAUGAG X 27 AUGAUGAUC 420
CGAA
AUCAUCAU AGAUGUCU
259 UAUCGUUA CUGAUGAG X 28 UCAGAUGUC 421
CGAA
ACAUCUGA UAACGAUA
261 CUUAUCGU CUGAUGAG X 29 AGAUGUCUA 422
CGAA
AGACAUCU ACGAUAAG
267 CCGCUCCU CUGAUGAG X 30 CUAACGAUA 423
CGAA
AUCGUUAG AGGAGCGG
277 ACCUGGCA CUGAUGAG X 31 GGAGCGGUU 924
CGAA
ACCGCUCC UGCCAGGU
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I.D.
tion RZ I.D. Substrate No.
No.
278 GACCUGGG CUGAUGAG X 32 GAGCGGUUU 425
CGAA
AACCGCUC GCCAGGUC
5 286 CAUCAUCC CUGAUGAG X 33 UGCCAGGUC 426
CGAA
ACCUGGCA GGAUGAUG
304 UAUCCGCA CUGAUGAG X 39 GCAGAGCUC 427
CGAA
AGCUCUGC UGCGGAUA
312 UCUCUCUU CUGAUGAG X 35 CUGCGGAUA 428
CGAA
10 AUCCGCAG AAGAGAGA
323 UCCCUGGC CUGAUGAG X 36 GAGAGACUU 429
CGAA
AGUCUCUC GCCAGGGA
336 UUCACUGU CUGAUGAG X 37 GGGAAAAUC 430
CGAA
AUUUUCCC ACAGUGAA
15 347 CGCCGUUC CUGAUGAG X 38 AGUGAAAUU 431
CGAA
AUUUCACU GAACGGCG
379 CUGUGAUG CUGAUGAG X 39 GACAGCCUA 432
CGAA
AGGCUGUC CAUCACAG
383 AGUUCUGU CUGAUGAG X 40 GCCUACAUC 933
CGAA
2 AUGUAGGC ACAGAACU
O
399 CCAUAUCU CUGAUGAG X 41 AGAACUGUC 934
CGAA
ACAGUUCU AGAUAUGG
399 GGGUACCA CUGAUGAG X 42 UGUCAGAUA 435
CGAA
AUCUGACA UGGUACCC
2 404 CAGGUGGG CUGAUGAG X 43 GAUAUGGUA 436
5 CGAA
ACCAUAUC CCCACCUG
414 CAGGGCAC CUGAUGAG X 44 CCACCUGUA 437
CGAA
ACAGGUGG GUGCCCUG
426 UGGUUUUC CUGAUGAG X 95 CCCUGGCUC 438
CGAA
3
O
AGCCAGGG GAAAACCA
443 AAGAUGGU CUGAUGAG X 96 GACAAGCUA 439
CGAA
AGCUUGUC ACCAUCUU
449 AUGCGUAA CUGAUGAG X 47 CUAACCAUC 490
CGAA
AUGGUUAG UUACGCAU
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I.D.
tion RZ I.D. Substrate No.
No.
451 CCAUGCGU CUGAUGAG X 98 AACCAUCUU 441
CGAA
AGAUGGUU ACGCAUGG
452 GCCAUGCG CUGAUGAG X 49 ACCAUCUUA 442
CGAA
AAGAUGGU CGCAUGGC
469 AUGUGAGA CUGAUGAG X 50 AUGGCAGUU 943
CGAA
ACUGCCAU UCUCACAU
465 CAUGUGAG CUGAUGAG X 51 UGGCAGUUU 449
CGAA
AACUGCCA CUCACAUG
966 UCAUGUGA CUGAUGAG X 52 GGCAGUUUC 945
CGAA
AAACUGCC UCACAUGA
468 CUUCAUGU CUGAUGAG X 53 CAGUUUCUC 446
CGAA
AGAAACUG ACAUGAAG
978 CCCGCAAG CUGAUGAG X 59 CAUGAAGUC 447
CGAA
ACUUCAUG CUUGCGGG
481 UUCCCCGC CUGAUGAG X 55 GAAGUCCUU 948
CGAA
AGGACUUC GCGGGGAA
502 CAUCAGUG CUGAUGAG X 56 CAACACAUC 449
CGAA
2 AUGUGUUG CACUGAUG
O
514 GCUUAUAG CUGAUGAG X 57 UGAUGGCUC 450
CGAA
AGCCAUCA CUAUAAGC
517 ACGGCUUA CUGAUGAG X 58 UGGCUCCUA 951
CGAA
AGGAGCCA UAAGCCGU
2 519 AGACGGCU CUGAUGAG X 59 GCUCCUAUA 452
5 CGAA
AUAGGAGC AGCCGUCU
526 UGAGGAAA CUGAUGAG X 60 UAAGCCGUC 453
CGAA
ACGGCUUA UUUCCUCA
528 AGUGAGGA CUGAUGAG X 61 AGCCGUCUU 454
CGAA
30
AGACGGCU UCCUCACU
529 CAGUGAGG CUGAUGAG X 62 GCCGUCUUU 455
CGAA
AAGACGGC CCUCACUG
530 UCAGUGAG CUGAUGAG X 63 CCGUCUUUC 456
CGAA
AAAGACGG CUCACUGA
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
533 UGAUCAGU CUGAUGAG X 64 UCUUUCGUC 457
CGAA
AGGAAAGA ACUGAUCA
540 CAGUUCCU CUGAUGAG X 65 UCACUGAUC 458
CGAA
AUCAGUGA AGGAACUG
555 CAAGAUCA CUGAUGAG X 66 UGAAACAUU 459
CGAA
AUGUUUCA UGAUCUUG
556 CCAAGAUC CUGAUGAG X 67 GAAACAUUU 460
CGAA
1 AAUGUUUC GAUCUUGG
O
560 GCCUCCAA CUGAUGAG X 68 CAUUUGAUC 461
CGAA
AUCAAAUG UUGGAGGC
562 CUGCCUCC CUGAUGAG X 69 UUUGAUCUU 462
CGAA
AGAUCAAA GGAGGCAG
15 580 UAAACAGA CUGAUGAG X 70 AGAUGGCUU 463
CGAA
AGCCAUCU UCUGUUUA
581 AUAAACAG CUGAUGAG X 71 GAUGGCUUU 464
CGAA
AAGCCAUC CUGUUUAU
582 AAUAAACA CUGAUGAG X 72 AUGGCUUUC 465
CGAA
2 AAAGCCAU UGUUUAUU
O
586 AGACAAUA CUGAUGAG X 73 CUUUCUGUU 466
CGAA
ACAGAAAG UAUUGUCU
587 GAGACAAU CUGAUGAG X 74 UUUCUGUUU 967
CGAA
AACAGAAA AUUGUCUC
25 588 UGAGACAA CUGAUGAG X 75 UUCUGUUUA 468
CGAA
AAACAGAA UUGUCUCA
590 CAUGAGAC CUGAUGAG X 76 CUGUUUAUU 469
CGAA
AUAAACAG GUCUCAUG
593 UCACAUGA CUGAUGAG X 77 UUUAUUGUC 470
CGAA
30
ACAAUAAA UCAUGUGA
595 UCUCACAU CUGAUGAG X 78 UAUUGUCUC 971
CGAA
AGACAAUA AUGUGAGA
619 CAGACACA CUGAUGAG X 79 GGUGGUGUA 472
CGAA
ACACCACC UGUGUCUG
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
625 CGGAGUCA CUGAUGAG X BO GUAUGUGUC 973
CGAA
ACACAUAC UGACUCCG
631 GAGUCACG CUGAUGAG X 81 GUCUGACUC 974
CGAA
AGUCAGAC CGUGACUC
639 CAAAACAG CUGAUGAG X 82 CCGUGACUC 475
CGAA
AGUCACGG CUGUUUUG
699 UGGUUCAA CUGAUGAG X 83 ACUCCUGUU 476
CGAA
ACAGGAGU UUGAACCA
695 CUGGUUCA CUGAUGAG X 84 CUCCUGUUU 477
CGAA
AACAGGAG UGAACCAG
646 GCUGGUUC CUGAUGAG X 85 UCCUGUUUU 978
CGAA
AAACAGGA GAACCAGC
661 ACCAUUCA CUGAUGAG X 86 GCCACAGUC 479
CGAA
ACUGUGGC UGAAUGGU
670 UGCUGCCA CUGAUGAG X 87 UGAAUGGUU 480
CGAA
ACCAUUCA UGGCAGCA
671 GUGCUGCC CUGAUGAG X 88 GAAUGGUUU 481
CGAA
2 AACCAUUC GGCAGCAC
O
683 UGAUCAUA CUGAUGAG X 89 AGCACACUC 482
CGAA
AGUGUGCU UAUGAUCA
685 CCUGAUCA CUGAUGAG X 90 CACACUCUA 483
CGAA
AGAGUGUG UGAUCAGG
690 GUGCACCU CUGAUGAG X 91 UCUAUGAUC 484
CGAA
AUCAUAGA AGGUGCAC
714 ACGAAGUU CUGAUGAG X 92 AUGUGGAUA 485
CGAA
AUCCACAU AACUUCGU
719 UGCUCACG CUGAUGAG X 93 GAUAAACUU 486
CGAA
AGUUUAUC CGUGAGCA
720 CUGCUCAC CUGAUGAG X 94 AUAAACUUC 487
CGAA
AAGUUUAU GUGAGCAG
731 GAAGUGGA CUGAUGAG X 95 GAGCAGCUU 488
CGAA
AGCUGCUC UCCACUUC
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
732 UGAAGUGG CUGAUGAG X 96 AGCAGCUUU 489
CGAA
AAGCUGCU CCACUUCA
733 CUGAAGUG CUGAUGAG X 97 GCAGCUUUC 490
CGAA
AAAGCUGC CACUUCAG
738 AUUUUCUG CUGAUGAG X 98 UUUCCACUU 491
CGAA
AGUGGAAA CAGAAAAU
739 CAUUUUCU CUGAUGAG X 99 UUCCACUUC 492
CGAA
AAGUGGAA AGAAAAUG
762 AUCCAGGA CUGAUGAG X 100 CAGGGCGUA 493
CGAA
ACGCCCUG UCCUGGAU
769 AGAUCCAG CUGAUGAG X 101 GGGCGUAUC 494
CGAA
AUACGCCC CUGGAUCU
771 AGUCUUUA CUGAUGAG X 102 UCCUGGAUC 495
CGAA
AUCCAGGA UAAAGACU
773 CCAGUCUU CUGAUGAG X 103 CUGGAUCUA 496
CGAA
AGAUCCAG AAGACUGG
801 AGACUGCU CUGAUGAG X 109 AGGAAGGUC 497
CGAA
2O ACCUUCCU AGCAGUCU
808 UCAUGGAA CUGAUGAG X 105 UCAGCAGUC 998
CGAA
ACUGCUGA UUCCAUGA
810 UCUCAUGG CUGAUGAG X 106 AGGAGUCUU 499
CGAA
AGACUGCU CCAUGAGA
2 811 UUCUCAUG CUGAUGAG X 107 GCAGUCUUC 500
5 CGAA
AAGACUGC CAUGAGAA
825 UGAGCCCA CUGAUGAG X 108 GAAUGUGUA 501
CGAA
ACACAUUC UGGGCUCA
832 AUCUCCUU CUGAUGAG X 109 UAUGGGCUC 502
CGAA
30
AGCCCAUA AAGGAGAU
841 AAAUAAAC CUGAUGAG X 110 AAGGAGAUC 503
CGAA
AUCUCCUU GUUUAUUU
894 GGCAAAUA CUGAUGAG X 111 GAGAUCGUU 504
CGAA
ACGAUCUC UAUUUGCC
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tion RZ I.D. Substrate No.
No.
845 CGGCAAAU CUGAUGAG X 112 AGAUCGUUU 505
CGAA
AACGAUCU AUUUGCCG
5 846 UCGGCAAA CUGAUGAG X 113 GAUCGUUUA 506
CGAA
AAACGAUC UUUGCCGA
898 AUUCGGCA CUGAUGAG X 119 UCGUUUAUU 507
CGAA
AUAAACGA UGCCGAAU
849 CAUUCGGC CUGAUGAG X 115 CGUUUAUUU 508
CGAA
10 AAUAAACG GCCGAAUG
870 CACAGAGC CUGAUGAG X 116 GUGGCAGUA 509
CGAA
ACUGCCAC GCUCUGUG
874 GGUCCACA CUGAUGAG X 117 CAGUAGCUC 510
CGAA
AGCUACUG UGUGGACC
15 887 UUCACAGA CUGAUGAG X 118 GACCCAGUU 511
CGAA
ACUGGGUC UCUGUGAA
888 AUUCACAG CUGAUGAG X 119 ACCCAGUUU 512
CGAA
AACUGGGU CUGUGAAU
889 UAUUCACA CUGAUGAG X 120 CCCAGUUUC 513
CGAA
2 AAACUGGG UGUGAAUA
0
897 GCUCAGCC CUGAUGAG X 121 CUGUGAAUA 514
CGAA
AUUCACAG GGCUGAGC
907 UCCUCACA CUGAUGAG X 122 GCUGAGCUU 515
CGAA
AGCUCAGC UGUGAGGA
25 908 UUCCUCAC CUGAUGAG X 123 CUGAGCUUU 516
CGAA
AAGCUCAG GUGAGGAA
935 ACAGAGCC CUGAUGAG X 124 AAUGGACUU 517
CGAA
AGUCCAUU GGCUCUGU
940 CCUUUACA CUGAUGAG X 125 ACUUGGCUC 518
CGAA
30
AGCCAAGU UGUAAAGG
944 CCAUCCUU CUGAUGAG X 126 GGCUCUGUA 519
CGAA
ACAGAGCC AAGGAUGG
960 CACGAAGU CUGAUGAG X 127 GGGAACCUC 520
CGAA
AGGUUCCC ACUUCGUG
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
969 CCACCACG CUGAUGAG X 128 ACCUCACUU 521
CGAA
AGUGAGGU CGUGGUGG
965 ACCACCAC CUGAUGAG X 129 CCUCACUUC 522
CGAA
AAGUGAGG GUGGUGGU
974 GUGCAGUG CUGAUGAG X 130 GUGGUGGUC 523
CGAA
ACCACCAC CACUGCAC
988 CCUUGAUG CUGAUGAG X 131 CACAGGCUA 524
CGAA
ld AGCCUGUG CAUCAAGG
992 CAGGCCUU CUGAUGAG X 132 GGCUACAUC 525
CGAA
AUGUAGCC AAGGCCUG
1016 GGGAGGGA CUGAUGAG X 133 GCAGGUGUU 526
CGAA
ACACCUGC UCCCUCCC
15 1017 UGGGAGGG CUGAUGAG X 134 CAGGUGUUU 527
CGAA
AACACCUG CCCUCCCA
1018 CUGGGAGG CUGAUGAG X 135 AGGUGUUUC 528
CGAA
AAACACCU CCUCCCAG
1022 UCAUCUGG CUGAUGAG X 136 GUUUCCCUC 529
CGAA
20 AGGGAAAC CCAGAUGA
1060 CUAGGCAA CUGAUGAG X 137 AAGCAAGUU 530
CGAA
ACUUGCUU UUGCCUAG
1061 ACUAGGCA CUGAUGAG X 138 AGCAAGUUU 531
CGAA
AACUUGCU UGCCUAGU
2 5 1062 CACUAGGC CUGAUGAG X 139 GCAAGUUUU 532
CGAA
AAACUUGC GCCUAGUG
1067 AUGGCCAC CUGAUGAG X 140 UUUUGCCUA 533
CGAA
AGGCAAAA GUGGCCAU
1076 AAUCUGCC CUGAUGAG X 141 GUGGCCAUU 534
CGAA
30
AUGGCCAC GGCAGAUU
1084 UUACCUGC CUGAUGAG X 142 UGGCAGAUU 535
CGAA
AUCUGCCA GCAGGUAA
1091 GAACUAGU CUGAUGAG X 143 UUGCAGGUA 536
CGAA
ACCUGCAA ACUAGUUC
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Posi- Seq. Seq.
I.D.
tion RZ I.D. Substrate No.
No.
1095 GGGAGAAC CUGAUGAG X 149 AGGUAACUA 537
CGAA
AGUUACCU GUUCUCCC
1098 GUUGGGAG CUGAUGAG X 195 UAACUAGUU 538
CGAA
ACUAGUUA CUCCCAAC
1099 AGUUGGGA CUGAUGAG X 146 AACUAGUUC 539
CGAA
AACUAGUU UCCCAACU
1101 ACAGUUGG CUGAUGAG X 147 CUAGUUCUC 540
CGAA
AGAACUAG CCAACUGU
1110 CAUGUCUG CUGAUGAG X 148 CCAACUGUA 541
CGAA
ACAGUUGG CAGACAUG
1122 ACAAACAU CUGAUGAG X 149 ACAUGAGUA 542
CGAA
ACUCAUGU AUGUUUGU
1127 GGUUGACA CUGAUGAG X 150 AGUAAUGUU 543
CGAA
ACAUUAGU UGUCAACC
1128 UGGUUGAC CUGAUGAG X 151 GUAAUGUUU 549
CGAA
AACAUUAC GUCAACCA
1131 UGUUGGUU CUGAUGAG X 152 AUGUUUGUC 595
CGAA
ACAAACAU AACCAACA
1149 GGGAGAUG CUGAUGAG X 153 AACAGAGUU 546
CGAA
ACUCUGUU CAUCUCCC
1145 CGGGAGAU CUGAUGAG X 154 ACAGAGUUC 547
CGAA
AACUCUGU AUCUCCCG
1148 UGUCGGGA CUGAUGAG X 155 GAGUUCAUC 548
CGAA
AUGAACUC UCCCGACA
1150 UGUGUCGG CUGAUGAG X 156 GUUCAUCUC 549
CGAA
AGAUGAAC CCGACACA
1163 AUACCCUC CUGAUGAG X 157 CACAACAUU 550
CGAA
AUGUUGUG GAGGGUAU
1170 AGUGAAGA CUGAUGAG X 158 UUGAGGGUA 551
CGAA
ACCCUCAA UCUUCACU
1172 AAAGUGAA CUGAUGAG X 159 GAGGGUAUC 552
CGAA
AUACCCUC UUCACUUU
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
1174 CAAAAGUG CUGAUGAG X 160 GGGUAUCUU 553
CGAA
AGAUACCC CACUUUUG
1175 ACAAAAGU CUGAUGAG X 161 GGUAUCUUC 559
CGAA
AAGAUACC ACUUUUGU
1179 AUCCACAA CUGAUGAG X 162 UCUUCACUU 555
CGAA
AGUGAAGA UUGUGGAU
1180 GAUCCACA CUGAUGAG X 163 CUUCACUUU 556
CGAA
1 AAGUGAAG UGUGGAUC
O
1181 UGAUCCAC CUGAUGAG X 169 UUCACUUUU 557
CGAA
AAAGUGAA GUGGAUCA
1188 ACAGCGGU CUGAUGAG X 165 UUGUGGAUC 558
CGAA
AUGCACAA ACCGCUGU
15 1203 GCCAACAG CUGAUGAG X 166 GUGUGGCUA 559
CGAA
AGCCACAC CUGUUGGC
1208 UGGUAGCC CUGAUGAG X 167 GCUACUGUU 560
CGAA
ACAGUAGC GGCUACCA
1213 GUGGCUGG CUGAUGAG X 168 UGUUGGCUA 561
CGAA
20 AGCCAACA CCAGCCAC
1229 UUUCCUAA CUGAUGAG X 169 CAGGAACUC 562
CGAA
AGUUCCUG UUAGGAAA
1231 UCUUUCCU CUGAUGAG X 170 GGAACUCUU 563
CGAA
AGAGUUCC AGGAAAGA
25 1232 UUCUUUCC CUGAUGAG X 171 GAACUCUUA 564
CGAA
AAGAGUUC GGAAAGAA
1292 UUCUACAA CUGAUGAG X 172 GAAAGAAUA 565
CGAA
AUUCUUUC UUGUAGAA
1249 AAUUCUAC CUGAUGAG X 173 AAGAAUAUU 566
CGAA
30
AUAUUCUU GUAGAAUU
1247 CAGAAUUC CUGAUGAG X 179 AAUAUUGUA 567
CGAA
ACAAUAUU GAAUUCUG
1252 GAUGACAG CUGAUGAG X 175 UGUAGAAUU 568
CGAA
AUUCUACA CUGUCAUC
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
1253 GGAUGACA CUGAUGAG X 176 GUAGAAUUC 569
CGAA
AAUUCUAC UGUCAUCC
1257 UUCAGGAU CUGAUGAG X 177 AAUUCUGUC 570
CGAA
ACAGAAUU AUCCUGAA
1260 GUCUUCAG CUGAUGAG X 178 UCUGUCAUC 571
CGAA
AUGACAGA CUGAAGAC
1277 UCUCUUAG CUGAUGAG X 179 CAGCAGCUU 572
CGAA
AGCUGCUG CUAAGAGA
1278 GUCUCUUA CUGAUGAG X 180 AGCAGCUUC 573
CGAA
AAGCUGCU UAAGAGAC
1280 CUGUCUCU CUGAUGAG X 181 CAGCUUCUA 574
CGAA
AGAAGCUG AGAGACAG
1291 CCUGUUGG CUGAUGAG X 182 AGACAGCUU 575
CGAA
AGCUGUCU CCAACAGG
1292 ACCUGUUG CUGAUGAG X 183 GACAGCUUC 576
CGAA
AAGCUGUC CAACAGGU
1301 AAUUUCAC CUGAUGAG X 189 CAACAGGUA 577
CGAA
2 ACCUGUUG GUGAAAUU
O
1309 GGCCUUUU CUGAUGAG X 185 AGUGAAAUU 578
CGAA
AUUUCACU AAAAGGCC
1310 UGGCCUUU CUGAUGAG X 186 GUGAAAUUA 579
CGAA
AAUUUCAC AAAGGCCA
1327 ACAUGACA CUGAUGAG X 187 AGUGCUGUC 580
CGAA
ACAGCACU UGUCAUGU
1331 CGGAACAU CUGAUGAG X 188 CUGUCUGUC 581
GGAA
ACAGACAG AUGUUCCG
1336 GGAACCGG CUGAUGAG X 189 UGUCAUGUU 582
CGAA
ACAUGACA CCGGUUCC
1337 CGGAACCG CUGAUGAG X 190 GUCAUGUUC 583
CGAA
AACAUGAC CGGUUCCG
1392 UAGACCGG CUGAUGAG X 191 GUUCCGGUU 584
CGAA
ACCGGAAC CCGGUCUA
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
1343 UUAGACCG CUGAUGAG X 192 UUCCGGUUC 585
CGAA
AACCGGAA CGGUCUAA
5 1348 GGUUCUUA CUGAUGAG X 193 GUUCCGGUC 586
CGAA
ACCGGAAC UAAGAACC
1350 UUGGUUCU CUGAUGAG X 194 UCCGGUCUA 587
CGAA
AGACCGGA AGAACCAA
1367 CUCAUCCA CUGAUGAG X 195 GAAUGGCUC 588
CGAA
10 AGCCAUUC UGGAUGAG
1389 AAGUAAAG CUGAUGAG X 196 AACCAGCUC 589
CGAA
AGCUGGUU CUUUACUU
1387 GGAAAGUA CUGAUGAG X 197 CAGCUCCUU 590
CGAA
AGGAGCUG UACUUUCC
15 1388 UGGAAAGU CUGAUGAG X 198 AGCUCCUUU 591
CGAA
AAGGAGCU ACUUUCCA
1389 CUGGAAAG CUGAUGAG X 199 GCUCCUUUA 592
CGAA
AAAGGAGC CUUUCCAG
1392 GUUCUGGA CUGAUGAG X 200 CCUUUACUU 593
CGAA
20 AGUAAAGG UCCAGAAC
1393 GGUUCUGG CUGAUGAG X 201 CUUUACUUU 594
CGAA
AAGUAAAG CCAGAACC
1394 GGGUUCUG CUGAUGAG X 202 UUUACUUUC 595
CGAA
AAAGUAAA CAGAACCC
2 5 1904 AUCUGAGU CUGAUGAG X 203 AGAACCCUU 596
CGAA
AGGGUUCU ACUCAGAU
1405 CAUCUGAG CUGAUGAG X 204 GAACCCUUA 597
CGAA
AAGGGUUC CUCAGAUG
1408 UUUCAUCU CUGAUGAG X 205 CCCUUACUC 598
CGAA
30
AGUAAGGG AGAUGAAA
1918 AUGUACUC CUGAUGAG X 206 GAUGAAAUU 599
CGAA
AUUUCAUC GAGUACAU
1423 AGAUGAUG CUGAUGAG X 207 AAUUGAGUA 600
CGAA
ACUCAAUU CAUCAUCU
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Posi- Seq. Seq.
I.D.
tion RZ I.D. Substrate No.
No:
1927 GUACAGAU CUGAUGAG X 208 GAGUACAUC 601
CGAA
AUGUACUC AUCUGUAC
1430 UUGGUACA CUGAUGAG X 209 UACAUCAUC 602
CGAA
AUGAUGUA UGUACCAA
1439 GGUGUUGG CUGAUGAG X 210 UCAUCUGUA 603
CGAA
ACAGAUGA CCAACACC
1956 CUUGGCUA CUGAUGAG X 211 GAAGAACUC 604
CGAA
AGUUCUUC UAGCCAAG
1958 UUCUUGGC CUGAUGAG X 212 AGAACUCUA 605
CGAA
AGAGUUCU GCCAAGAA
1476 GGAGAGUG CUGAUGAG X 213 CACGGCCUA 606
CGAA
AGGCCGUG CACUCUCC
1481 GUGUUGGA CUGAUGAG X 214 CCUACACUC 607
CGAA
AGUGUAGG UCCAACAC
1483 UUGUGUUG CUGAUGAG X 215 UACACUCUC 608
CGAA
AGAGUGUA CAACACAA
1993 GGCCUCUG CUGAUGAG X 216 AACACAAUC 609
CGAA
2 AUUGUGUU CAGAGGCC
O
1508 GUGGGACC CUGAUGAG X 217 CCACAACUA 610
CGAA
AGUUGUGG GGUCCCAC
1512 AGCUGUGG CUGAUGAG X 218 AACUAGGUC 611
CGAA
ACCUAGUU CCACAGCU
1521 GGGUAAAU CUGAUGAG X 219 CCACAGCUA 612
CGAA
AGCUGUGG AUUUACCC
1524 CAGGGGUA CUGAUGAG X 220 CAGCUAAUU 613
CGAA
AUUAGCUG UACCCCUG
1525 CCAGGGGU CUGAUGAG X 221 AGCUAAUUU 614
CGAA
AAUUAGCU ACCCCUGG
1526 UCCAGGGG CUGAUGAG X 222 GCUAAUUUA 615
CGAA
AAAUUAGC CCCCUGGA
1543 GCUGUCCU CUGAUGAG X 223 GAUGGGCUC 616
CGAA
AGCCCAUC AGGACAGC
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
1585 CCAUGUCC CUGAUGAG X 224 AACAGAAUU 617
CGAA
AUUCUGUU GGACAUGG
1595 CUUCCUGG CUGAUGAG X 225 GACAUGGUA 618
CGAA
ACCAUGUC CCAGGAAG
1621 AAUGAUUG CUGAUGAG X 226 GGCCAGCUA 619
CGAA
AGCUGGCC CAAUCAUU
1626 CUGGGAAU CUGAUGAG X 227 GCUACAAUC 620
CGAA
IO AUUGUAGC AUUCCCAG
1629 CACCUGGG CUGAUGAG X 228 ACAAUCAUU 621
CGAA
AUGAUUGU CCCAGGUG
1630 CCACCUGG CUGAUGAG X 229 CAAUCAUUC 622
CGAA
AAUGAUUG CCAGGUGG
15 1640 ACAGGCUG CUGAUGAG X 230 CAGGUGGUU 623
CGAA
ACCACCUG CAGCCUGU
1641 CACAGGCU CUGAUGAG X 231 AGGUGGUUC 629
CGAA
AACCACCU AGCCUGUG
1682 GACUUCUC CUGAUGAG X 232 AAGCCCCUU 625
CGAA
2 AGGGGCUU GAGAAGUC
O
1690 AACCAUCU CUGAUGAG X 233 UGAGAAGUC 626
CGAA
ACUUCUCA AGAUGGUU
1698 GGCAAAUA CUGAUGAG X 234 CAGAUGGUU 627
CGAA
ACCAUCUG UAUUUGCC
2 1699 GGGCAAAU CUGAUGAG X 235 AGAUGGUUU 628
S CGAA
AACCAUCU AUUUGCCC
1700 UGGGCAAA CUGAUGAG X 236 GAUGGUUUA 629
CGAA
AAACCAUC UUUGCCCA
1702 CCUGGGCA CUGAUGAG X 237 UGGUUUAUU 630
CGAA
30
AUAAACCA UGCCCAGG
1703 UCCUGGGC CUGAUGAG X 238 GGUUUAUUU 631
CGAA
AAUAAACC GCCCAGGA
1713 UGGAUCUC CUGAUGAG X 239 CCCAGGAUA 632
CGAA
AUCCUGGG GAGAUCCA
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
1719 AAAUCUUG CUGAUGAG X 240 AUAGAGAUC 633
CGAA
AUCUCUAU CAAGAUUU
1726 UUUCUGAA CUGAUGAG X 291 UCCAAGAUU 639
CGAA
AUCUUGGA UUCAGAAA
1727 AUUUCUGA CUGAUGAG X 242 CCAAGAUUU 635
CGAA
AAUCUUGG UCAGAAAU
1728 GAUUUCUG CUGAUGAG X 243 CAAGAUUUU 636
CGAA
AAAUCUUG CAGAAAUC
1729 AGAUUUCU CUGAUGAG X 249 AAGAUUUUC 637
CGAA
AAAAUCUU AGAAAUCU
1736 UUGUGAUA CUGAUGAG X 245 UCAGAAAUC 638
CGAA
AUUUCUGA UAUCACAA
1738 UGUUGUGA CUGAUGAG X 246 AGAAAUCUA 639
CGAA
AGAUUUCU UCACAACA
1740 GAUGUUGU CUGAUGAG X 247 AAAUCUAUC 640
CGAA
AUAGAUUU ' ACAACAUC
1798 UCCGCAUU CUGAUGAG X 248 CACAACAUC 641
CGAA
2 AUGUUGUG AAUGCGGA
O
1758 UUUACUCU CUGAUGAG X 249 AUGCGGAUC 642
CGAA
AUCCGCAU AGAGUAAA
1764 GAUGCCUU CUGAUGAG X 250 AUCAGAGUA 643
CGAA
ACUCUGAU AAGGCAUC
1772 CUGGAGGA CUGAUGAG X 251 AAAGGCAUC 644
CGAA
AUGCCUUU UCCUCCAG
1774 UGCUGGAG CUGAUGAG X 252 AGGCAUCUC 695
CGAA
AGAUGCCU CUCCAGCA
1777 CAGUGCUG CUGAUGAG X 253 CAUCUCCUC 646
CGAA
AGGAGAUG CAGCACUG
1787 GUGGCAGG CUGAUGAG X 254 AGCACUGUC 647
CGAA
ACAGUGCU CCUGCCAC
1805 UGGGAGAA CUGAUGAG X 255 CAACAGCUA 698
CGAA
AGCUGUUG UUCUCCCA
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I.D.
tion RZ I.D. Substrate No.
No.
1807 CCUGGGAG CUGAUGAG X CGAA256 ACAGCUAUU 649
AUAGCUGU CUCCCAGG
1808 CCCUGGGA CUGAUGAG X CGAA257 CAGCUAUUC 650
AAUAGCUG UCCCAGGG
1810 UGCCCUGG CUGAUGAG X CGAA258 GCUAUUCUC 651
AGAAUAGC CCAGGGCA
1825 UAGGAGGG CUGAUGAG X CGAA259 CAACACAUU 652
AUGUGUUG CCCUCCUA
1826 GUAGGAGG CUGAUGAG X CGAA260 AACACAUUC 653
AAUGUGUU CCUCCUAC
1830 GGGGGUAG CUGAUGAG X CGAA261 CAUUCCCUC 654
AGGGAAUG CUACCCCC
1833 CCGGGGGG CUGAUGAG X CGAA262 UCCCUCCUA 655
AGGAGGGA CCCCCCGG
1854 AUUCCUGA CUGAUGAG X CGAA263 CAGAGAAUU 656
AUUCUCUG UCAGGAAU
1855 UAUUCCUG CUGAUGAG X CGAA264 AGAGAAUUU 657
2 AAUUCUCU CAGGAAUA
a
1856 CUAUUCCU CUGAUGAG X CGAA265 GAGAAUUUC 658
AAAUUCUC AGGAAUAG
1863 UAGGCCAC CUGAUGAG X CGAA266 UCAGGAAUA 659
AUUCCUGA GUGGCCUA
2 1871 GGAGGGGC CUGAUGAG X CGAA267 AGUGGCCUA 660
5
AGGCCACU GCCCCUCC
1878 GGUUACAG CUGAUGAG X CGAA268 UAGCCCCUC 661
AGGGGCUA CUGUAACC
1883 ACAAUGGU CUGAUGAG X CGAA269 CCUCCUGUA 662
30
ACAGGAGG ACCAUUGU
1889 GGCUGGAC CUGAUGAG X CGAA270 GUAACCAUU 663
AUGGUUAC GUCCAGCC
1892 GAUGGCUG CUGAUGAG X CGAA271 ACCAUUGUC 664
ACAAUGGU CAGCCAUC
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
1900 CAGAAGCU CUGAUGAG X 272 CCAGCCAUC 665
CGAA
AUGGCUGG AGCUUCUG
5 1905 UCCUGCAG CUGAUGAG X 273 CAUCAGCUU 666
CGAA
AGCUGAUG CUGCAGGA
1906 GUCCUGCA CUGAUGAG X 274 AUCAGCUUC 667
CGAA
AAGCUGAU UGCAGGAC
1921 UCUGGGCC CUGAUGAG X 275 ACAGAUGUU 668
CGAA
10 ACAUCUGU GGCCCAGA
1931 UGGCGGGA CUGAUGAG X 276 GCCCAGAUU 669
CGAA
AUCUGGGC UCCCGCCA
1932 GUGGCGGG CUGAUGAG X 277 CCCAGAUUU 670
CGAA
AAUCUGGG CCCGCCAC
15 1933 AGUGGCGG CUGAUGAG X 278 CCAGAUUUC 671
CGAA
AAAUCUGG CCGCCACU
1942 UGGGGUUG CUGAUGAG X 279 CCGCCACUC 672
CGAA
AGUGGCGG CAACCCCA
1971 AGGGGUCC CUGAUGAG X 280 CCCCAACUU 673
CGAA
2 O AGUUGGGG GGACCCCU
1980 GCGGGUAG CUGAUGAG X 281 GGACCCCUA 674
CGAA
AGGGGUCC CUACCCGC
1983 UGAGCGGG CUGAUGAG X 282 CCCCUACUA 675
CGAA
AGUAGGGG CCCGCUCA
25 1990 AAAAGCCU CUGAUGAG X 283 UACCCGCUC 676
CGAA
AGCGGGUA AGGCUUUU
1996 GGGCAGAA CUGAUGAG X 289 CUCAGGCUU 677
CGAA
AGCCUGAG UUCUGCCC
1997 UGGGCAGA CUGAUGAG X 285 UCAGGCUUU 678
CGAA
3O
AAGCCUGA UCUGCCCA
1998 CUGGGCAG CUGAUGAG X 286 CAGGCUUUU 679
CGAA
AAAGCCUG CUGCCCAG
1999 GCUGGGCA CUGAUGAG X 287 AGGCUUUUC 680
CGAA
AAAAGCCU UGCCCAGC
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Posi- Seq. Seq.
I.D.
tion RZ I.D. Substrate No.
No.
2016 AGCCUGGG CUGAUGAG X CGAA28B AGGUGGCUA 681
AGCCACCU CCCAGGCU
2025 CUUAGCAG CUGAUGAG X CGAA289 CCCAGGCUA 682
AGCCUGGG CUGCUAAG
2031 ACGAGUCU CUGAUGAG X CGAA290 CUACUGCUA 683
AGCAGUAG AGACUCGU
2037 GGAAGUAC CUGAUGAG X CGAA291 CUAAGACUC 684
AGUCUUAG GUACUUCC
2040 CUGGGAAG CUGAUGAG X CGAA292 AGACUCGUA 685
ACGAGUCU CUUCCCAG
2043 AAACUGGG CUGAUGAG X CGAA293 CUCGUACUU 686
AGUACGAG CGCAGUUU
2044 CAAACUGG CUGAUGAG X CGAA294 UCGUACUUC 687
AAGUACGA CCAGUUUG
2050 CCACACCA CUGAUGAG X CGAA295 UUCCCAGUU 688
ACUGGGAA UGGUGUGG
2051 CCCACACC CUGAUGAG X CGAA296 UCCCAGUUU 689
2 AACUGGGA GGUGUGGG
O
2065 GAGUCUGA CUGAUGAG X CGAA297 GGGCAGCUU 690
AGCUGCCC UCAGACUC
2066 GGAGUCUG CUGAUGAG X CGAA298 GGCAGCUUU 691
AAGCUGCC CAGACUCC
2067 UGGAGUCU CUGAUGAG X CGAA299 GCAGCUUUC 692
AAAGCUGC AGACUCCA
2073 GGAGGAUG CUGAUGAG X CGAA300 UUCAGACUC 693
AGUCUGAA CAUCCUCC
2077 UGAAGGAG CUGAUGAG X CGAA301 GACUCCAUC 699
AUGGAGUC CUCCUUCA
2080 AGCUGAAG CUGAUGAG X CGAA302 UCCAUCCUC 695
AGGAUGGA CUUCAGCU
2083 UGGAGCUG CUGAUGAG X CGAA303 AUCCUCCUU 696
AGGAGGAU CAGCUCCA
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Posi- Seq. Seq.
I.D.
tion RZ I.D. Substrate No.
No.
2084 AUGGAGCU CUGAUGAG X CGAA309 UCCUCCUUC 697
AAGGAGGA AGCUCCAU
2089 GGGACAUG CUGAUGAG X CGAA305 CUUCAGCUC 698
AGCUGAAG CAUGUCCC
2095 CAGGGAGG CUGAUGAG X CGAA306 CUCCAUGUC 699
ACAUGGAG CCUCCCUG
2099 GCACCAGG CUGAUGAG X CGAA307 AUGUCCCUC 700
AGGGACAU CCUGGUGC
2119 CACCAGGC CUGAUGAG X CGAA308 AACUGCAUC 701
AUGCAGUU GCCUGGUG
2137 GACUAGGG CUGAUGAG X CGAA309 UGCUGCCUA 702
AGGCAGCA CCCUAGUC
2142 GGUGAGAC CUGAUGAG X CGAA310 CCUACCCUA 703
AGGGUAGG GUCUCACC
2145 AUUGGUGA CUGAUGAG X CGAA311 ACCCUAGUC 704
ACUAGGGU UCACCAAU
2147 CGAUUGGU CUGAUGAG X CGAA312 CCUAGUCUC 705
2 AGACUAGG ACCAAUCG
O
2154 AGAUCCAC CUGAUGAG X CGAA313 UCACCAAUC 706
AUUGGUGA GUGGAUCU
2161 CAAAGUUA CUGAUGAG X CGAA314 UCGUGGAUC 707
AUCCACGA UAACUUUG
2 2163 AGCAAAGU CUGAUGAG X CGAA315 GUGGAUCUA 708
5
AGAUCCAC ACUUUGCU
2167 CAGGAGCA CUGAUGAG X CGAA316 AUCUAACUU 709
AGUUAGAU UGCUCCUG
2168 UCAGGAGC CUGAUGAG X CGAA317 UCUAACUUU 710
30
AAGUUAGA GCUCCUGA
2172 AGUCUCAG CUGAUGAG X CGAA318 ACUUUGCUC 711
AGCAAAGU CUGAGACU
2200 GUGUCUGG CUGAUGAG X CGAA319 AGGACAAUU 712
AUUGUCCU CCAGACAC
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
2201 CGUGUCUG CUGAUGAG X 320 GGACAAUUC 713
CGAA
AAUUGUCC CAGACACG
2231 UGUGGCCA CUGAUGAG X 321 GUGGGUGUC 719
CGAA
ACACCCAC UGGCCACA
2259 ACGAUGAU CUGAUGAG X 322 AGCAGCCUC 715
CGAA
AGGCUGCU AUCAUCGU
2262 UGAACGAU CUGAUGAG X 323 AGCCUCAUC 716
CGAA
AUGAGGCU AUCGUUCA
2265 ACUUGAAC CUGAUGAG X 324 CUCAUCAUC 717
CGAA
AUGAUGAG GUUCAAGU
2268 AGAACUUG CUGAUGAG X 325 AUCAUCGUU 718
CGAA
ACGAUGAU CAAGUUCU
2269 UAGAACUU CUGAUGAG X 326 UCAUCGUUC 719
GGAA
AACGAUGA AAGUUCUA
2279 CUCACUAG CUGAUGAG X 327 GUUCAAGUU 720
CGAA
ACUUGAAC CUAGUGAG
2275 GCUCACUA CUGAUGAG X 328 UUCAAGUUC 721
CGAA
AACUUGAA UAGUGAGC
2277 UUGCUCAC CUGAUGAG X 329 CAAGUUCUA 722
CGAA
AGAACUUG GUGAGCAA
2291 GGUUGUUG CUGAUGAG X 330 CAACAUGUU 723
CGAA
ACAUGUUG CAACAACC
2292 CGGUUGUU CUGAUGAG X 331 AACAUGUUC 724
CGAA
AACAUGUU AACAACCG
2330 UCCUGGAA CUGAUGAG X 332 CCUGAGGUC 725
CGAA
ACCUCAGG UUCCAGGA
2332 UCUCCUGG CUGAUGAG X 333 UGAGGUCUU 726
CGAA
AGACCUCA CCAGGAGA
2333 AUCUCCUG CUGAUGAG X 334 GAGGUCUUC 727
CGAA
AAGACCUC CAGGAGAU
2347 CCAGCAUG CUGAUGAG X 335 GAUGCUGUC 728
CGAA
ACAGCAUC CAUGCUGG
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Posi- Seq. Seq.
I.D.
tion RZ I.D. Substrate No.
No.
2361 GUUGCUCU CUGAUGAG X CGAA336 UGGGAGAUC 729
AUCUCCCA AGAGCAAC
2379 CAUUGUUG CUGAUGAG X CGAA337 CAACAGCUA 730
AGCUGUUG CAACAAUG
2389 GAUCAGGG CUGAUGAG X CGAA338 UGAAGAAUU 731
AUUCUUCA CCCUGAUC
2390 AGAUCAGG CUGAUGAG X CGAA339 GAAGAAUUC 732
AAUUCUUC CCUGAUCU
2397 CAUAGUUA CUGAUGAG X CGAA340 UCCCUGAUC 733
AUCAGGGA UAACUAUG
2399 AACAUAGU CUGAUGAG X CGAA341 CCUGAUCUA 734
AGAUCAGG ACUAUGUU
2903 GGGAAACA CUGAUGAG X CGAA342 AUCUAACUA 735
AGUUAGAU UGUUUCCC
2407 AGGGGGGA CUGAUGAG X CGAA343 AACUAUGUU 736
ACAUAGUU UCCCCCCU
2408 AAGGGGGG CUGAUGAG X CGAA344 ACUAUGUUU 737
AACAUAGU CCCCCCUU
2409 AAAGGGGG CUGAUGAG X CGAA345 CUAUGUUUC 738
AAACAUAG CCCCCUUU
2416 AUUCUGAA CUGAUGAG X CGAA346 UCCCCCCUU 739
AGGGGGGA UUCAGAAU
2 2417 UAUUCUGA CUGAUGAG X CGAA347 CCCCCCUUU 790
5
AAGGGGGG UCAGAAUA
2418 CUAUUCUG CUGAUGAG X CGAA348 CCCCCUUUU 741
AAAGGGGG CAGAAUAG
2419 UCUAUUCU CUGAUGAG X CGAA349 CCCCUUUUC 742
~pGGGG AGAAUAGA
2425 AAUAGUUC CUGAUGAG X CGAA350 UUCAGAAUA 743
AUUCUGAA GAACUAUU
2431 CACCCCAA CUGAUGAG X CGAA351 AUAGAACUA 744
AGUUCUAU UUGGGGUG
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
2433 CUCACCCC CUGAUGAG X 352 AGAACUAUU 745
CGAA
AUAGUUCU GGGGUGAG
5 2445 CCACCCCU CUGAUGAG X 353 GUGAGGAUA 746
CGAA
AUCCUCAC AGGGGUGG
2966 CAAACAGU CUGAUGAG X 354 GAAAAAAUC 747
CGAA
AUUUUUUC ACUGUUUG
2972 UAAAAACA CUGAUGAG X 355 AUCACUGUU 748
CGAA
10 ACAGUGAU UGUUUUUA
2473 UUAAAAAC CUGAUGAG X 356 UCACUGUUU 749
CGAA
AACAGUGA GUUUUUAA
2476 UUUUUAAA CUGAUGAG X 357 CUGUUUGUU 750
CGAA
ACAAACAG UUUAAAAA
15 2477 CUUUUUAA CUGAUGAG X 358 UGUUUGUUU 751
CGAA
AACAAACA UUAAAAAG
2978 GCUUUUUA CUGAUGAG X 359 GUUUGUUUU 752
CGAA
AAACAAAC UAAAAAGC
2979 UGCUUUUU CUGAUGAG X 360 UUUGUUUUU 753
CGAA
2 AAAACAAA AAAAAGCA
0
2980 UUGCUUUU CUGAUGAG X 361 UUGUUUUUA 754
CGAA
AAAAACAA AAAAGCAA
2991 UACAGAAA CUGAUGAG X 362 AAGCAAAUC 755
CGAA
AUUUGCUU UUUCUGUA
2 2493 UUUACAGA CUGAUGAG X 363 GCAAAUCUU 756
5 CGAA
AGAUUUGC UCUGUAAA
2494 GUUUACAG CUGAUGAG X 369 CAAAUCUUU 757
CGAA
AAGAUUUG CUGUAAAC
2995 UGUUUACA CUGAUGAG X 365 AAAUCUUUC 758
CGAA
3
O
Ap,AGAUUU UGUAAACA
2499 AUUCUGUU CUGAUGAG X 366 CUUUCUGUA 759
CGAA
ACAGAAAG AACAGAAU
2508 GGAACUUU CUGAUGAG X 367 AACAGAAUA 760
CGAA
AUUCUGUU AAAGUUCC
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Posi- Seq. Seq. I.D.
tion RZ I.D. Substrate No.
No.
2514 GGGAGAGG CUGAUGAG X 368 AUAAAAGUU 761
CGAA
ACUUUUAU CCUCUCCC
2515 AGGGAGAG CUGAUGAG X 369 UAAAAGUUC 762
CGAA
AACUUUUA CUCUCCCU
2518 GGAAGGGA CUGAUGAG X 370 AAGUUCCUC 763
CGAA
AGGAACUU UCCCUUCC
2520 AGGGAAGG CUGAUGAG X 371 GUUCCUCUC 764
CGAA
AGAGGAAC CCUUCCCU
2529 GGGAAGGG CUGAUGAG X 372 CUCUCCCUU 765
CGAA
AGGGAGAG CCCUUCCC
2525 AGGGAAGG CUGAUGAG X 373 UCUCCCUUC 766
CGAA
AAGGGAGA CCUUCCCU
2529 GGUGAGGG CUGAUGAG X 374 CCUUCCCUU 767
CGAA
AGGGAAGG CCCUCACC
2530 GGGUGAGG CUGAUGAG X 375 CUUCCCUUC 768
CGAA
AAGGGAAG CCUCACCC
2539 UCAGGGGU CUGAUGAG X 376 CCUUCCCUC 769
CGAA
2 AGGGAAGG ACCCCUGA
O
2548 AAAGGGGG CUGAUGAG X 377 UGACAUGUA 770
CGAA
ACAUGUCA CCCCCUUU
2555 AGAAGGGA CUGAUGAG X 378 UACCCCCUU 771
CGAA
AGGGGGUA UCCCUUCU
2556 CAGAAGGG CUGAUGAG X 379 ACCCCCUUU 772
CGAA
AAGGGGGU CCCUUCUG
2557 CCAGAAGG CUGAUGAG X 380 CCCCCUUUC 773
CGAA
AAAGGGGG CCUUCUGG
2561 ACAGCCAG CUGAUGAG X 381 CUUUCCCUU 774
CGAA
AGGGAAAG CUGGCUGU
2562 AACAGCCA CUGAUGAG X 382 UUUCCCUUC 775
CGAA
AAGGGAAA UGGCUGUU
2570 AGCAGGGG CUGAUGAG X 383 CUGGCUGUU 776
CGAA
ACAGCCAG CCCCUGCU
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Posi- Seq. Seq.
I.D.
tion RZ I.D. Substrate No.
No.
2571 GAGCAGGG CUGAUGAG X 384 UGGCUGUUC 777
CGAA
AACAGCCA CCCUGCUC
2579 AGGCAACA CUGAUGAG X 385 CCCCUGCUC 778
CGAA
AGCAGGGG UGUUGCCU
2583 UAGGAGGC CUGAUGAG X 386 UGCUCUGUU 779
CGAA
ACAGAGCA GCCUCCUA
2588 UACCUUAG CUGAUGAG X 387 UGUUGCCUC 780
CGAA
AGGCAACA CUAAGGUA
2591 UGUUACCU CUGAUGAG X 388 UGCCUCCUA 781
CGAA
AGGAGGCA AGGUAACA
2596 AUAAAUGU CUGAUGAG X 389 CCUAAGGUA 782
CGAA
ACCUUAGG ACAUUUAU
2601 UUUUUAUA CUGAUGAG X 390 GGUAACAUU 783
CGAA
AUGUUACC UAUAAAAA
2602 UUUUUUAU CUGAUGAG X 391 GUAACAUUU 784
CGAA
AAUGUUAC AUAAAAAA
2603 UUUUUUUA CUGAUGAG X 392 UAACAUUUA 785
CGAA
AAAUGUUA UAAAAAAA
2605 UUUUUUUU CUGAUGAG X 393 ACAUUUAUA 786
CGAA
AUAAAUGU AAAAAAAA
30
CA 02324421 2000-09-26
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TABLE I V: HAIRPIN RIBOZYME SEøUENCES AND TARGET SITES FOR ARNT
Posi- Seq. Seq.
I.D.
tion RZ No. Substrate I.D.
No.
6 GGGAGG AGAA GCCA ACCAGAGAAACA787 UGGCG GCU CCUCCC899
GUACAUUACCUGGUA
92 UGGUAC AGAR GAUG ACCAGAGAAACA788 CAUCA GAU GUACCA850
GUACAUUACCUGGUA
253 UUAGAC AGAA GAUC ACCAGAGAAACA789 GAUCA GAU GUCUAA851
X GUACAUUACCUGGUA
274 CUGGCA AGAA GCUC ACCAGAGAAACA790 GAGCG GUU UGCCAG852
GUACAUUACCUGGUA
287 CUCAUC AGAA GACC ACCAGAGAAACA791 GGUCG GAU GAUGAG853
GUACAUUACCUGGUA
374 GAUGUA AGAA GUCA ACCAGAGAAACA792 UGACA GCC UACAUC854
X GUACAUUACCUGGUA
411 GGGCAC AGAA GGUG ACCAGAGAAACA793 CACCU GUA GUGCCC855
GUACAUUACCUGGUA
461 GUGAGA AGAA GCCA ACCAGAGAAACA794 UGGCA GUU UCUCAC856
GUACAUUACCUGGUA
506 GGAGCC AGAR GUGG ACCAGAGAAACA795 CCACU GAU GGCUCC857
GUACAUUACCUGGUA
523 GGAAA AGAR GCUU ACCAGAGAAACA796 GCC GUC UUUCCU 858
X GUACAUUACCUGGUA
536 UUCCUG AGAA GUGA ACCAGAGAAACA797 UCACU GAU CAGGAA859
GUACAUUACCUGGUA
572 GCC AGAR GCUG ACCAGAGAAACA798 CAGCA GAU GGCUUU860
X GUACAUUACCUGGUA
583 CAAUA AGAR GAAA ACCAGAGAAACA799 UUUCU GUU UAUUGU861
X GUACAUUACCUGGUA
626 CACGGA AGAR GACA ACCAGAGAAACA800 UGUCU GAC UCCGUG862
X GUACAUUACCUGGUA
641 GUUCAA AGAA GGAG ACCAGAGAAACA801 CUCCU GUU UUGAAC863
GUACAUUACCUGGUA
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Posi- Seq. Seq.
I.D.
tionRZ No. Substrate I.D.
No.
658 CAUUCA AGAA GUGG ACCAGAGAAACA802 CCACA GUC UGAAUG864
GUACAUUACCUGGUA
701 CACAUC AGAA GGGU ACCAGAGAAACA803 CCCA GAU GAUGUG865
X GUACAUUACCUGGUA
727 GUGGAA AGAA GCUC ACCAGAGAAACA809 GAGCA GCU UUCCAC866
GUACAUUACCUGGUA
805 UGGAA AGAA GCUG ACCAGAGAAACA805 CAGCA GUC UUCCAU867
GUACAUUACCUGGUA
867 CAGAGC AGAA GCCA ACCAGAGAAACA806 UGGCA GUA GCUCUG868
GUACAUUACCUGGUA
884 CACAGA AGAA GGGU ACCAGAGAAACA807 CCCA GUU UCUGUG869
GUACAUUACCUGGUA
918 UCCUGC AGAA GUUC ACCAGAGAAACA808 GAACA GAU GCAGGA870
X GUACAUUACCUGGUA
1025GUCAUC AGAA GGGA ACCAGAGAAACA809 UCCCA GAU GAUGAC871
GUACAUUACCUGGUA
1080CCUGCA AGAA GCCA ACCAGAGAAACA810 UGGCA GAU UGCAGG872
GUACAUUACCUGGUA
1107UGUCUG AGAA GUUG ACCAGAGAAACA811 CAACU GUA CAGACA873
X GUACAUUACCUGGUA
1191CCACAC AGAR GUGA ACCAGAGAAACA812 UCACC GCU GUGUGG874
2 5 X GUACAUUACCUGGUA
1205GUAGCC AGAR GUAG ACCAGAGAAACA813 CUACU GUU GGCUAC875
GUACAUUACCUGGUA
1273CUUAGA AGAR GCUG ACCAGAGAAACA814 CAGCA GCU UCUAAG876
X GUACAUUACCUGGUA
1287GUUGGA AGAA GUCU ACCAGAGAAACA815 GACA GCU UCCAAC877
GUACAUUACCUGGUA
1324UGACA AGAA GCAC ACCAGAGAAACA816 GUGCU GUC UGUCAU878
GUACAUUACCUGGUA
1339GACCGG AGAA GGAA ACCAGAGAAACA817 UUCCG GUU CCGGUC879
X GUACAUUACCUGGUA
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Posi- Seq. Seq.
I.D.
tionRZ No. Substrate I.D.
No.
1345UUCUUA AGAA GGAA ACCAGAGAAACA818 UUCCG GUC UAAGAA880
X GUACAUUACCUGGUA
5
1380UAAAGG AGAA GGUU ACCAGAGAAACA819 CCA GCU CCUUUA 881
X GUACAUUACCUGGUA
1409UUUC AGAR GAGU ACCAGAGAAACA820 CUCA GAU GAAAUU 882
GUACAUUACCUGGUA
1431UGUUGG AGAR GAUG ACCAGAGAAACA821 CAUCU GUA CCAACA883
10
X GUACAUUACCUGGUA
1471GUGUA AGAA GUGG ACCAGAGAAACA822 CCACG GCC UACACU884
GUACAUUACCUGGUA
1549GGUGCC AGAA GUCC ACCAGAGAAACA823 GGACA GCU GGCACC885
15 GUACAUUACCUGGUA
1642GUCACA AGAR GAAC ACCAGAGAAACA829 GUUCA GCC UGUGAC886
GUACAUUACCUGGUA
1691UAAACC AGAA GACU ACCAGAGAAACA825 GUCA GAU GGUUUA 887
X GUACAUUACCUGGUA
r
1?54CUCUG AGAA GCAU ACCAGAGAAACA826 UGCG GAU CAGAGU 888
GUACAUUACCUGGUA
1784GGCAGG AGAR GUGC ACCAGAGAAACA827 GCACU GUC CCUGCC889
GUACAUUACCUGGUA
1840UCUGCC AGAR GGGG ACCAGAGAAACA828 CCCCG GCC GGCAGA890
2 5 GUACAUUACCUGGUA
1901UGCAGA AGAR GAUG ACCAGAGAAACA829 CAUCA GCU UCUGCA891
GUACAUUACCUGGUA
1915GCCAAC AGAA GUCC ACCAGAGAAACA830 GGACA GAU GUUGGC892
GUACAUUACCUGGUA
30 1927CGGGAA AGAR GGGC ACCAGAGAAACA831 GCCCA GAU UUCCCG893
GUACAUUACCUGGUA
1986GCCUG AGAA GGUA ACCAGAGAAACA832 UACCC GCU CAGGCU894
X GUACAUUACCUGGUA
2000CUGCUG AGAR GAAA ACCAGAGAAACA833 UUUCU GCC CAGCAG895
X GUACAUUACCUGGUA
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Posi- Seq. Seq.
I.D.
tionRZ No. Substrate I.D.
No.
2047CACCA AGAA GGGA ACCAGAGAAACA839 UCCCA GUU UGGUGU896
X GUACAUUACCUGGUA
2061UCUGAA AGAR GCCC ACCAGAGAAACA835 GGGCA GCU UUCAGA897
X GUACAUUACCUGGUA
2068GAUGGA AGAA GAAA ACCAGAGAAACA836 UUUCA GAC UCCAUC898
GUACAUUACCUGGUA
2085CAUGG AGAA GAAG ACCAGAGAAACA837 CUUCA GCU CCAUGU899
GUACAUUACCUGGUA
2129GUAGGC AGAR GCAC ACCAGAGAAACA838 GUGCU GCU GCCUAC900
GUACAUUACCUGGUA
2132GGGUA AGAA GCAG ACCAGAGAAACA839 CUGCU GCC UACCCU901
GUACAUUACCUGGUA
2185CUGCA AGAR GUCC ACCAGAGAAACA890 GGACA GAC UGCAGG902
X GUACAUUACCUGGUA
2254UGAUGA AGAA GCUG ACCAGAGAAACA841 CAGCA GCC UCAUCA903
GUACAUUACCUGGUA
2320CCUCA AGAA GGCC ACCAGAGAAACA842 GGCCA GCC UGAGGU904
GUACAUUACCUGGUA
2344GCAUG AGAA GCAU ACCAGAGAAACA893 UGCU GUC CAUGCU905
X GUACAUUACCUGGUA
2393GUUAG AGAA GGGA ACCAGAGAAACA899 UCCCU GAU CUAACU906
2 5 GUACAUUACCUGGUA
2969CA AGAA GUGA ACCAGAGAAACA845 UCACU GUU UGUUUU907
GUACAUUACCUGGUA
2567CAGGGG AGAA GCCA ACCAGAGAAACA846 UGGCU GUU CCCCUG908
GUACAUUACCUGGUA
30 2575CAACAG AGAR GGGG ACCAGAGAAACA847 CCCCU GCU CUGUUG909
X GUACAUUACCUGGUA
2580GGAGGC AGAR GAGC ACCAGAGAAACA848 GCUCU GUU GCCUCC910
GUACAUUACCUGGUA
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TABLE V: HAMMERHEAD RIBOZYMES AND TARGET SITES FOR TIE
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
13 CAAGAAGG CUGAUGAG911 UGUGCUGUU 1612
X CGAA ACAGCACA CCUUCUUG
19 GCAAGAAG CUGAUGAG912 GUGCUGUUC 1613
X CGAA AACAGCAC CUUCUUGC
17 GAGGCAAG CUGAUGAG913 CUGUUCCUU 1614
X CGAA AGGAACAG CUUGCCUC
18 AGAGGCAA CUGAUGAG914 UGUUCCUUC 1615
X CGAA AAGGAACA UUGCCUCU
UUAGAGGC CUGAUGAG915 UUCCUUCUU 1616
X CGAA AGAAGGAA GCCUCUAA
ACAAGUUA CUGAUGAG916 UCUUGCCUC 1617
15 X CGAA AGGCAAGA UAACUUGU
27 UUACAAGU CUGAUGAG917 UUGCCUCUA 1618
X CGAA AGAGGCAA ACUUGUAA
31 UUGUUUAC CUGAUGAG918 CUCUAACUU 1619
X CGAA AGUUAGAG GUAAACAA
2 0 34 GUCUUGUU CUGAUGAG919 UAACUUGUA 1620
X CGAA ACAAGUUA AACAAGAC
45 CGUCCUAG CUGAUGAG920 CAAGACGUA 1621
X CGAA ACGUCUUG CUAGGACG
48 CAUCGUCC CUGAUGAG921 GACGUACUA 1622
2 5 X CGAA AGUACGUC GGACGAUG
59 CUUUCCAU CUGAUGAG922 ACGAUGCUA 1623
X CGAA AGCAUCGU AUGGAAAG
69 CGGUUUGU CUGAUGAG923 UGGAAAGUC 1624
X CGAA ACUUUCCA ACAAACCG
84 CUUUCAAA CUGAUGAG924 CGCUGGGUU 1625
X CGAA ACCCAGCG UUUGAAAG
85 CCUUUCAA CUGAUGAG925 GCUGGGUUU 1626
X CGAA AACCCAGC UUGAAAGG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
86 UCCUUUCA CUGAUGAG926 CUGGGUUUU 1627
X CGAA AAACCCAG UGAAAGGA
87 AUCCUUUC CUGAUGAG927 UGGGUUUUU 1628
X CGAA AAAACCCA GAAAGGAU
96 GUCCCAAG CUGAUGAG928 GAAAGGAUC 1629
X CGAA AUCCUUUC CUUGGGAC
99 GAGGUCCC CUGAUGAG929 AGGAUCCUU 1630
1Q X CGAA AGGAUCCU GGGACCUC
107 AUGUGCAU CUGAUGAG930 UGGGACCUC 1631
X CGAA AGGUCCCA AUGCACAU
116 UUUCCACA CUGAUGAG931 AUGCACAUU 1632
X CGAA AUGUGCAU UGUGGAAA
117 GUUUCCAC CUGAUGAG932 UGCACAUUU 1633
X CGAA AAUGUGCA GUGGAAAC
139 CUUCCCCA CUGAUGAG933 GGAGAGAUU 1634
X CGAA AUCUCUCC UGGGGAAG
140 GCUUCCCC CUGAUGAG934 GAGAGAUUU 1635
2 0 X CGAA AAUCUCUC GGGGAAGC
156 UGGCUAAA CUGAUGAG935 CAUGGACUC 1636
X CGAA AGUCCAUG UUUAGCCA
158 GCUGGCUA CUGAUGAG936 UGGACUCUU 1637
X CGAA AGAGUCCA UAGCCAGC
159 AGCUGGCU CUGAUGAG937 GGACUCUUU 1638
X CGAA AAGAGUCC AGCCAGCU
160 AAGCUGGC CUGAUGAG938 GACUCUUUA 1639
X CGAA AAAGAGUC GCCAGCUU
168 AGAGAACU CUGAUGAG939 ~ AGCCAGCUU 1640
X CGAA AGCUGGCU AGUUCUCU
169 CAGAGAAC CUGAUGAG940 GCCAGCUUA 1691
X CGAA AAGCUGGC GUUCUCUG
172 CCACAGAG CUGAUGAG941 AGCUUAGUU 1642
X CGAA ACUAAGCU CUCUGUGG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
173 UCCACAGA CUGAUGAG942 GCUUAGUUC 1643
X CGAA AACUAAGC UCUGUGGA
175 ACUCCACA CUGAUGAG943 UUAGUUCUC 1649
X CGAA AGAACUAA UGUGGAGU
184 AGCAAGCU CUGAUGAG994 UGUGGAGUC 1645
X CGAA ACUCCACA AGCUUGCU
189 AAAGGAGC CUGAUGAG995 AGUCAGCUU 1646
X CGAA AGCUGACU GCUCCUUU
193 CCAGAAAG CUGAUGAG946 AGCUUGCUC 1647
X CGAA AGCAAGCU CUUUCUGG
196 GUUCCAGA CUGAUGAG947 UUGCUCCUU 1648
X CGAA AGGAGCAA UCUGGAAC
197 AGUUCCAG CUGAUGAG948 UGCUCCUUU 1649
X CGAA AAGGAGCA CUGGAACU
198 CAGUUCCA CUGAUGAG949 GCUCCUUUC 1650
X CGAA AAAGGAGC UGGAACUG
225 UCAAGAUC CUGAUGAG950 CAUGGACUU 1651
2 O X CGAA AGUCCAUG GAUCUUGA
229 UUGAUCAA CUGAUGAG951 GACUUGAUC 1652
X CGAA AUCAAGUC UUGAUCAA
231 AAUUGAUC CUGAUGAG952 CUUGAUCUU 1653
X CGAA AGAUCAAG GAUCAAUU
235 AGGGAAUU CUGAUGAG953 AUCUUGAUC 1654
X CGAA AUCAAGAU AAUUCCCU
239 AGGUAGGG CUGAUGAG954 UGAUCAAUU 1655
X CGAA AUUGAUCA CCCUACCU
240 GAGGUAGG CUGAUGAG955 GAUCAAUUC 1656
X CGAA AAUUGAUC CCUACCUC
244 ACAAGAGG CUGAUGAG956 AAUUCCCUA 1657
X CGAA AGGGAAUU CCUCUUGU
248 AGAUACAA CUGAUGAG957 CCCUACCUC 1658
X CGAA AGGUAGGG UUGUAUCU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
250 UCAGAUAC CUGAUGAG958 CUACCUCUU 1659
X CGAA AGAGGUAG GUAUCUGA
5 253 GCAUCAGA CUGAUGAG959 CCUCUUGUA 1660
X CGAA ACAAGAGG UCUGAUGC
255 CAGCAUCA CUGAUGAG960 UCUUGUAUC 1661
X CGAA AUACAAGA UGAUGCUG
270 AGGUGAGA CUGAUGAG961 UGAAACAUC 1662
10 X CGAA AUGUUUCA UCUCACCU
272 GCAGGUGA CUGAUGAG962 AAACAUCUC 1663
X CGAA AGAUGUUU UCACCUGC
279 AUGCAGGU CUGAUGAG963 ACAUCUCUC 1664
X CGAA AGAGAUGU ACCUGCAU
15 283 CCAGAGGC CUGAUGAG964 ACCUGCAUU 1665
X CGAA AUGCAGGU GCCUCUGG
288 GCCACCCA CUGAUGAG965 CAUUGCCUC 1666
X CGAA AGGCAAUG UGGGUGGC
313 CCUAUGGU CUGAUGAG966 GAGCCCAUC 1667
2~ X CGAA RUGGGCUC ACCAUAGG
3-19 UCCCUUCC CUGAUGAG967 AUCACCAUA 1668
X CGAA AUGGUGAU GGAAGGGA
330 AGGCUUCA CUGAUGAG968 AAGGGACUU 1669
X CGAA AGUCCCUU UGAAGCCU
25
331 AAGGCUUC CUGAUGAG969 AGGGACUUU 1670
X CGAA AAGUCCCU GAAGCCUU
339 GGUUCAUU CUGAUGAG970 UGAAGCCUU 1671
X CGAA AGGCUUCA AAUGAACC
340 UGGUUCAU CUGAUGAG971 GAAGCCUUA 1672
30
X CGAA AAGGCUUC AUGAACCA
359 UUCCAGCG CUGAUGAG972 ACCAGGAUC 1673
X CGAA AUCCUGGU CGCUGGAA
370 UCUUGAGU CUGAUGAG973 CUGGAAGUU 1674
X CGAA ACUUCCAG ACUCAAGA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
371 AUCUUGAG CUGAUGAG974 UGGAAGUUA 1675
X CGAA AACUUCCA CUCAAGAU
374 CACAUCUU CUGAUGAG975 AAGUUACUC 1676
X CGAA AGUAACUU AAGAUGUG
398 AACUUUUU CUGAUGAG976 AAUGGGCUA 1677
X CGAA AGCCCAUU AAAAAGUU
406 UUCCAAAC CUGAUGAG977 AAAAAAGUU 1678
X CGAA ACUUUUUU GUUUGGAA
909 CUCUUCCA CUGAUGAG978 AAAGUUGUU 1679
X CGAA ACAACUUU UGGAAGAG
410 UCUCUUCC CUGAUGAG979 AAGUUGUUU 1680
X CGAA AACAACUU GGAAGAGA
428 GAUCUUAC CUGAUGAG980 AAAAGGCUA 1681
X CGAA AGCCUUUU GUAAGAUC
931 AUUGAUCU CUGAUGAG981 AGGCUAGUA 1682
X CGAA ACUAGCCU AGAUCAAU
436 GCACCAUU CUGAUGAG982 AGUAAGAUC 1683
2 O X CGAA AUCUUACU AAUGGUGC
946 ACAGAAAU CUGAUGAG983 AUGGUGCUU 1684
X CGAA AGCACCAU AUUUCUGU
447 CACAGAAA CUGAUGAG984 UGGUGCUUA 1685
X CGAA AAGCACCA UUUCUGUG
44g UUCACAGA CUGAUGAG985 GUGCUUAUU 1686
X CGAA AUAAGCAC UCUGUGAA
950 CUUCACAG CUGAUGAG986 UGCUUAUUU 1687
X CGAA AAUAAGCA CUGUGAAG
451 CCUUCACA CUGAUGAG987 GCUUAUUUC 1688
X CGAA AAAUAAGC UGUGAAGG
466 UCUCCUCG CUGAUGAG988 GGGCGAGUU 1689
X CGAA ACUCGCCC CGAGGAGA
467 CUCUCCUC CUGAUGAG989 GGCGAGUUC 1690
X CGAA AACUCGCC GAGGAGAG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
481 CGUAUCCU CUGAUGAG990 GAGGCAAUC 1691
X CGAA AUUGCCUC AGGAUACG
487 AUGGUUCG CUGAUGAG991 AUCAGGAUA 1692
X CGAA AUCCUGAU CGAACCAU
506 AGCUUGUU CUGAUGAG992 AGAUGCGUC 1693
X CGAA ACGCAUCU AACAAGCU
515 UAGGAAGG CUGAUGAG993 AACAAGCUU 1694
X CGAA AGCUUGUU CCUUCCUA
516 GUAGGAAG CUGAUGAG994 ACAAGCUUC 1695
X CGAA AAGCUUGU CUUCCUAC
519 CUGGUAGG CUGAUGAG995 AGCUUCCUU 1696
X CGAA AGGAAGCU CCUACCAG
520 GCUGGUAG CUGAUGAG996 GCUUCCUUC 1697
X CGAA AAGGAAGC CUACCAGC
523 GUAGCUGG CUGAUGAG997 UCCUUCCUA 1698
X CGAA AGGAAGGA CCAGCUAC
530 AGUUAAAG CUGAUGAG998 UACCAGCUA 1699
2 O X CGAA AGCUGGUA CUUUAACU
533 CAUAGUUA CUGAUGAG999 CAGCUACUU 1700
X CGAA AGUAGCUG UAACUAUG
534 UCAUAGUU CUGAUGAG1000 AGCUACUUU 1701
X CGAA AAGUAGCU AACUAUGA
535 GUCAUAGU CUGAUGAG1001 GCUACUUUA 1702
X CGAA AAAGUAGC ACUAUGAC
539 CACAGUCA CUGAUGAG1002 CUUUAACUA 1703
X CGAA AGUUAAAG UGACUGUG
560 GUUCACGU CUGAUGAG1003 AGGGAGAUA 1704
X CGAA AUCUCCCU ACGUGAAC
571 UUGAAAGA CUGAUGAG1004 GUGAACAUA 1705
X CGAA AUGUUCAC UCUUUCAA
573 UUUUGAAA CUGAUGAG1005 GAACAUAUC 1706
X CGAA AUAUGUUC UUUCAAAA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
575 CUUUUUGA CUGAUGAG1006 ACAUAUCUU 1707
X CGAA AGAUAUGU UCAAAAAG
576 CCUUUUUG CUGAUGAG1007 CAUAUCUUU 1708
X CGAA AAGAUAUG CAAAAAGG
577 ACCUUUUU CUGAUGAG1008 AUAUCUUUC 1709
X CGAA AAAGAUAU AAAAAGGU
586 UUAAUCAA CUGAUGAG1009 AAAAAGGUA 1710
X CGAA ACCUUUUU UUGAUUAA
588 CUUUAAUC CUGAUGAG1010 AAAGGUAUU 1711
X CGAA AUACCUUU GAUUAAAG
592 UCUUCUUU CUGAUGAG1011 GUAUUGAUU 1712
X CGAA AUCAAUAC AAAGAAGA
593 UUCUUCUU CUGAUGAG1012 UAUUGAUUA 1713
X CGAA AAUCAAUA AAGAAGAA
613 UUUUUGUA CUGAUGAG1013 GCAGUGAUU 1?14
X CGAA AUCACUGC UACAAAAA
619 AUUUUUGU CUGAUGAG1014 CAGUGAUUU 1715
2 O X CGAA AAUCACUG ACAAAAAU
615 CAUUUUUG CUGAUGAG1015 AGUGAUUUA 1716
X CGAA AAAUCACU CAAAAAUG
626 GAUGAAGG CUGAUGAG1016 AAAAUGGUU 1717
X CGAA ACCAUUUU CCUUCAUC
627 GGAUGAAG CUGAUGAG1017 AAAUGGUUC 1718
X CGAA AACCAUUU CUUCAUCC
630 AAUGGAUG CUGAUGAG1018 UGGUUCCUU 1719
X CGAA AGGAACCA CAUCCAUU
631 GAAUGGAU CUGAUGAG1019 GGUUCCUUC 1720
X CGAA AAGGAACC AUCCAUUC
634 ACUGAAUG CUGAUGAG1020 UCCUUCAUC 1721
X CGAA AUGAAGGA CAUUCAGU
638 GGGCACUG CUGAUGAG1021 UCAUCCAUU 1722
X CGAA AUGGAUGA CAGUGCGC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
639 GGGGCACU CUGAUGAG1022 CAUCCAUUC 1723
X CGAA AAUGGAUG AGUGCCCC
658 AUAUCAGG CUGAUGAG1023 CAUGAAGUA 1724
X CGAA ACUUCAUG CCUGAUAU
665 UUCUAGAA CUGAUGAG1024 UACCUGAUA 1725
X CGAA AUCAGGUA UUCUAGAA
667 ACUUCUAG CUGAUGAG1025 CCUGAUAUU 1726
X CGAA AUAUCAGG CUAGAAGU
668 UACUUCUA CUGAUGAG1026 CUGAUAUUC 1727
X CGAA AAUAUCAG UAGAAGUA
670 UGUACUUC CUGAUGAG1027 GAUAUUCUA 1728
X CGAA AGAAUAUC GAAGUACA
676 GGCAGGUG CUGAUGAG1028 CUAGAAGUA 1729
X CGAA ACUUCUAG CACCUGCC
686 CUGAGCAU CUGAUGAG1029 ACCUGCCUC 1730
X CGAA AGGCAGGU AUGCUCAG
692 CUGGGGCU CUGAUGAG1030 CUCAUGCUC 1731
X CGAA AGCAUGAG AGCCCCAG
714 UGGCGGAG CUGAUGAG1031 UGGAGUGUA 1732
X CGAA ACACUCCA CUCGGCCA
717 ACCUGGCC CUGAUGAG1032 AGUGUACUC 1733
X CGAA AGUACACU GGCCAGGU
726 CUCCUAUA CUGAUGAG1033 GGCCAGGUA 1739
X CGAA ACCUGGCC UAUAGGAG
728 UCCUCCUA CUGAUGAG1034 CCAGGUAUA 1735
X CGAA AUACCUGG UAGGAGGA
730 UUUCCUCC CUGAUGAG1035 AGGUAUAUA 1736
X CGAA AUAUACCU GGAGGAAA
742 GAGGUGAA CUGAUGAG1036 GGAAACCUC 1737
X CGAA AGGUUUCC UUCACCUC
794 CCGAGGUG CUGAUGAG1037 AAACCUCUU 1738
X CGAA AGAGGUUU CACCUCGG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
745 GCCGAGGU CUGAUGAG1038 AACCUCUUC 1739
X CGAA AAGAGGUU ACCUCGGC
750 UGAAGGCC CUGAUGAG1039 CUUCACCUC 1790
X CGAA AGGUGAAG GGCCUUCA
756 GCCUGGUG CUGAUGAG1040 CUCGGCCUU 1741
X CGAA AGGCCGAG CACCAGGC
757 AGCCUGGU CUGAUGAG1041 UCGGCCUUC 1742
X CGAA AAGGCCGA ACCAGGCU
769 CUCCGGAC CUGAUGAG1042 AGGCUGAUA 1793
X CGAA AUCAGCCU GUCCGGAG
772 CAUCUCCG CUGAUGAG1093 CUGAUAGUC 1749
X CGAA ACUAUCAG CGGAGAUG
815 AGUACAGA CUGAUGAG1044 GCAACCAUC 1745
X CGAA AUGGUUGC UCUGUACU
817 GCAGUACA CUGAUGAG1045 AACCAUCUC 1746
X CGAA AGAUGGUU UGUACUGC
821 ACAAGCAG CUGAUGAG1046 AUCUCUGUA 1747
2 O X CGAA ACAGAGAU CUGCUUGU
B27 GUUCAUAC CUGAUGAG1047 GUACUGCUU 1748
X CGAA AGCAGUAC GUAUGAAC
830 AUUGUUCA CUGAUGAG1048 CUGCUUGUA 1749
X CGAA ACAAGCAG UGAACAAU
g4q UCAUGGCA CUGAUGAG1099 AAUGGUGUC 1750
X CGAA ACACCAUU UGCCAUGA
857 UUCUCCAG CUGAUGAG1050 AUGAAGAUA 1751
X CGAA AUCUUCAU CUGGAGAA
871 GGAGGGCA CUGAUGAG1051 GAAUGCAUU 1752
X CGAA AUGCAUUC UGCCCUCC
872 AGGAGGGC CUGAUGAG1052 AAUGCAUUU 1753
X CGAA AAUGCAUU GCCCUCCU
878 AAACCCAG CUGAUGAG1053 UUUGCCCUC 1754
X CGAA AGGGCAAA CUGGGUUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
885 UUCCCAUA CUGAUGAG1054 UCCUGGGUU 1755
X CGAA ACCCAGGA UAUGGGAA
886 CUUCCCAU CUGAUGAG1055 CCUGGGUUU 1756
X CGAA AACCCAGG AUGGGAAG
887 CCUUCCCA CUGAUGAG1056 CUGGGUUUA 1757
X CGAA AAACCCAG UGGGAAGG
911 CAGUUCAC CUGAUGAG1057 AGAAGGCUU 1758
X CGAA AGCCUUCU GUGAACUG
927 UUCUGCCA CUGAUGAG1058 GCACACGUU 1759
X CGAA ACGUGUGC UGGCAGAA
928 GUUCUGCC CUGAUGAG1059 CACACGUUU 1760
X CGAA AACGUGUG GGCAGAAC
938 UUCUUUAC CUGAUGAG1060 GCAGAACUU 1761
X CGAA AGUUCUGC GUAAAGAA
941 CCUUUCUU CUGAUGAG1061 GAACUUGUA 1762
X CGAA ACAAGUUC AAGAAAGG
975 ACACAUAA CUGAUGAG1062 AUGCAAGUC 1763
2 O X CGAA ACUUGCAU UUAUGUGU
977 GAACACAU CUGAUGAG1063 GCAAGUCUU 1769
X CGAA AGACUUGC AUGUGUUC
978 AGAACACA CUGAUGAG1064 CAAGUCUUA 1765
X CGAA AAGACUUG UGUGUUCU
2 5
ggq GGAGACAG CUGAUGAG1065 UUAUGUGUU 1766
X CGAA ACACAUAA CUGUCUCC
985 GGGAGACA CUGAUGAG1066 UAUGUGUUC 1767
X CGAA AACACAUA UGUCUCCC
989 GUCAGGGA CUGAUGAG1067 UGUUCUGUC 1768
30
X CGAA ACAGAACA UCCCUGAC
991 GGGUCAGG CUGAUGAG1068 UUCUGUCUC 1769
X CGAA AGACAGAA CCUGACCC
1002 AACACCCA CUGAUGAG1069 UGACCCCUA 1770
X CGAA AGGGGUCA UGGGUGUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1010 GGCACAGG CUGAUGAG1070 AUGGGUGUU 1771
X CGAA ACACCCAU CCUGUGCC
1011 UGGCACAG CUGAUGAG1071 UGGGUGUUC 1772
X CGAA AACACCCA CUGUGCCA
1039 GCACUGCA CUGAUGAG1072 GGAAGGGUC 1773
X CGAA ACCCUUCC UGCAGUGC
1064 CCCGUAAA CUGAUGAG1073 ACCCUGGUU 1774
X CGAA ACCAGGGU UUUACGGG
1065 GCCCGUAA CUGAUGAG1074 CCCUGGUUU 1775
X CGAA AACCAGGG UUACGGGC
1066 GGCCCGUA CUGAUGAG1075 CCUGGUUUU 1776
X CGAA AAACCAGG UACGGGCC
1067 UGGCCCGU CUGAUGAG1076 CUGGUUUUU 1777
X CGAA AAAACCAG ACGGGCCA
1068 CUGGCCCG CUGAUGAG1077 UGGUUUUUA 1778
X CGAA AAAAACCA CGGGCCAG
1079 AAGCUUAC CUGAUGAG1078 GGCCAGAUU 1779
X CGAA AUCUGGCC GUAAGCUU
1082 CCUAAGCU CUGAUGAG1079 CAGAUUGUA 1780
X CGAA ACAAUCUG AGCUUAGG
1087 CUGCACCU CUGAUGAG1080 UGUAAGCUU 1781
X CGAA AGCUUACA AGGUGCAG
1088 GCUGCACC CUGAUGAG1081 GUAAGCUUA 1782
X CGAA AAGCUUAC GGUGCAGC
1121 UUGGAAGC CUGAUGAG1082 UGUGUGAUC 1783
X CGAA AUCACACA GCUUCCAA
1125 AUCCUUGG CUGAUGAG1083 UGAUCGCUU 1789
X CGAA AGCGAUCA CCAAGGAU
1126 CAUCCUUG CUGAUGAG1084 GAUCGCUUC 1785
X CGAA AAGCGAUC CAAGGAUG
1136 AGAGCAGA CUGAUGAG1085 AAGGAUGUC 1786
X CGAA ACAUCCUU UCUGCUCU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1138 GGAGAGCA CUGAUGAG1086 GGAUGUCUC 1787
X CGAA AGACAUCC UGCUCUCC
1143 AUCCUGGA CUGAUGAG1087 UCUCUGCUC 1788
X CGAA AGCAGAGA UCCAGGAU
1145 CCAUCCUG CUGAUGAG1088 UCUGCUCUC 1789
X CGAA AGAGCAGA CAGGAUGG
1162 UCACACUG CUGAUGAG1089 CAGGGGCUC 1790
X CGAA AGCCCCUG CAGUGUGA
1183 AUCCUCGG CUGAUGAG1090 GAAGGCAUA 1791
X CGAA AUGCCUUC CCGAGGAU
1204 AAAUCCAC CUGAUGAG1091 CCAAAGAUA 1792
X CGAA AUCUUUGG GUGGAUUU
1211 AUCUGGCA CUGAUGAG1092 UAGUGGAUU 1793
X CGAA AUCCACUA UGCCAGAU
1212 GAUCUGGC CUGAUGAG1093 AGUGGAUUU 1794
X CGAA AAUCCACU GCCAGAUC
1220 UUCUAUAU CUGAUGAG1099 UGCCAGAUC 1795
X CGAA AUCUGGCA AUAUAGAA
1223 UACUUCUA CUGAUGAG1095 CAGAUCAUA 1796
X CGAA AUGAUCUG UAGAAGUA
1225 UUUACUUC CUGAUGAG1096 GAUCAUAUA 1797
X CGAA AUAUGAUC GAAGUAAA
1231 CCACUGUU CUGAUGAG1097 AUAGAAGUA 1798
X CGAA ACUUCUAU AACAGUGG
1241 AUUAAAUU CUGAUGAG1098 ACAGUGGUA 1799
X CGAA ACCACUGU AAUUUAAU
1245 UGGGAUUA CUGAUGAG1099 UGGUAAAUU 1800
X CGAA AUUUACCA UAAUCCCA
1246 AUGGGAUU CUGAUGAG1100 GGUAAAUUU 1801
X CGAA AAUUUACC AAUCCCAU
1247 AAUGGGAU CUGAUGAG1101 GUAAAUUUA 1802
X CGAA AAAUUUAC AUCCCAUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1250 GCAAAUGG CUGAUGAG1102 AAUUUAAUC 1803
X CGAA AUUAAAUU CCAUUUGC
1255 GCUUUGCA CUGAUGAG1103 AAUCCCAUU 1804
X CGAA AUGGGAUU UGCAAAGC
1256 AGCUUUGC CUGAUGAG1109 AUCCCAUUU 1805
X CGAA AAUGGGAU GCAAAGCU
1265 CCAGCCAG CUGAUGAG1105 GCAAAGCUU 1806
X CGAA AGCUUUGC CUGGCUGG
1266 GCCAGCCA CUGAUGAG1106 CAAAGCUUC 1807
X CGAA AAGCUUUG UGGCUGGC
1279 UUAGUAGG CUGAUGAG1107 UGGCCGCUA 1808
X CGAA AGCGGCCA CCUACUAA
1283 UUCAUUAG CUGAUGAG1108 CGCUACCUA 1809
X CGAA AGGUAGCG CUAAUGAA
1286 UUCUUCAU CUGAUGAG1109 UACCUACUA 1810
X CGAA AGUAGGUA AUGAAGAA
1327 UUUGGAUG CUGAUGAG1110 ACAGUGCUC 1811
X CGAA AGCACUGU CAUCCAAA
1331 GUCUUUUG CUGAUGAG1111 UGCUCCAUC 1812
X CGAA AUGGAGCA CAAAAGAC
1341 UAUGGUUA CUGAUGAG1112 AAAAGACUU 1813
X CGAA AGUCUUUU UAACCAUA
1342 GUAUGGUU CUGAUGAG1113 AAAGACUUU 1819
X CGAA AAGUCUUU AACCAUAC
1393 CGUAUGGU CUGAUGAG1119 AAGACUUUA 1815
X CGAA AAAGUCUU ACCAUACG
1349 AUGAUCCG CUGAUGAG1115 UUAACCAUA 1816
X CGAA AUGGUUAA CGGAUCAU
1355 UGAGAAAU CUGAUGAG1116 AUACGGAUC 1817
X CGAA AUCCGUAU AUUUCUCA
1358 UACUGAGA CUGAUGAG1117 CGGAUCAUU 1818
X CGAA AUGAUCCG UCUCAGUA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1359 CUACUGAG CUGAUGAG1118 GGAUCAUUU 1819
X CGAA AAUGAUCC CUCAGUAG
1360 GCUAGUGA CUGAUGAG1119 GAUCAUUUC 1820
X CGAA AAAUGAUC UCAGUAGC
1362 UGGCUACU CUGAUGAG1120 UCAUUUCUC 1821
X CGAA AGAAAUGA AGUAGCCA
1366 AAUAUGGG CUGAUGAG1121 UUCUCAGUA 1822
X CGAA ACUGAGAA GCCAUAUU
1372 AUGGUGAA CUGAUGAG1122 GUAGCCAUA 1823
X CGAA AUGGCUAC UUCACCAU
1379 GGAUGGUG CUGAUGAG1123 AGCCAUAUU 1824
X CGAA AUAUGGCU CACCAUCC
1375 UGGAUGGU CUGAUGAG1124 GCCAUAUUC 1825
X GGAA AAUAUGGC ACCAUCCA
1381 AUCCGGUG CUGAUGAG1125 UUCACCAUC 1826
X CGAA AUGGUGAA CACCGGAU
1390 GGGGGGAG CUGAUGAG1126 CACCGGAUC 1827
X CGAA AUCCGGUG CUCCCCCC
1393 UCAGGGGG CUGAUGAG1127 CGGAUCCUC 1828
X CGAA AGGAUCCG CCCCCUGA
1904 AAACUCCU CUGAUGAG1128 CCCUGACUC 1829
X CGAA AGUCAGGG AGGAGUUU
1411 CAGACCCA CUGAUGAG1129 UCAGGAGUU 1830
X CGAA ACUCCUGA UGGGUCUG
1412 GCAGACCC CUGAUGAG1130 CAGGAGUUU 1831
X CGAA AACUCCUG GGGUCUGC
1417 ACACUGCA CUGAUGAG1131 GUUUGGGUC 1832
X CGAA ACCCAAAC UGCAGUGU
1958 AAAUGUUG CUGAUGAG1132 AAAGCCCUU 1833
X CGAA AGGGCUUU CAACAUUU
1959 GAAAUGUU CUGAUGAG1133 AAGCCCUUC 1839
X CGAA AAGGGCUU AACAUUUC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1965 UUAACAGA CUGAUGAG1134 UUCAACAUU 1835
X CGAA AUGUUGAA UCUGUUAA
1466 UUUAACAG CUGAUGAG1135 UCAACAUUU 1836
X CGAA AAUGUUGA CUGUUAAA
1467 CUUUAACA CUGAUGAG1136 CAACAUUUC 1837
X CGAA AAAUGUUG UGUUAAAG
1471 AGAACUUU CUGAUGAG1137 AUUUCUGUU 1838
X CGAA ACAGAAAU AAAGUUCU
1472 AAGAACUU CUGAUGAG1138 UUUCUGUUA 1839
X CGAA AACAGAAA AAGUUCUU
1477 UUUGGAAG CUGAUGAG1139 GUUAAAGUU 1840
X CGAA ACUUUAAC CUUCCAAA
1978 CUUUGGAA CUGAUGAG1140 UUAAAGUUC 1841
X CGAA AACUUUAA UUCCAAAG
1480 GGCUUUGG CUGAUGAG1191 AAAGUUCUU 1842
X CGAA AGAACUUU CCAAAGCC
1481 GGGCUUUG CUGAUGAG1142 AAGUUCUUC 1893
2 O X CGAA AAGAACUU CAAAGCCC
1510 CCAGUGUC CUGAUGAG1143 AACGUGAUU 1844
X CGAA AUCACGUU GACACUGG
1523 AGCAAAGU CUGAUGAG1144 CUGGACAUA 1845
X CGAA AUGUCCAG ACUUUGCU
2 5
1527 UGACAGCA CUGAUGAG1145 ACAUAACUU 1846
X CGAA AGUUAUGU UGCUGUCA
1528 AUGACAGC CUGAUGAG1146 CAUAACUUU 1847
X CGAA AAGUUAUG GCUGUCAU
1534 AUGUUGAU CUGAUGAG1147 UUUGCUGUC 1848
30
X CGAA ACAGCAAA AUCAACAU
1537 CUGAUGUU CUGAUGAG1148 GCUGUCAUC 1849
X CGAA AUGACAGC AACAUCAG
1543 UCAGAGCU CUGAUGAG1149 AUCAACAUC 1850
X CGAA AUGUUGAU AGCUCUGA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1548 AAGGCUCA CUGAUGAG1150 CAUCAGCUC 1851
X CGAA AGCUGAUG UGAGCCUU
1556 CCCAAAGU CUGAUGAG1151 CUGAGCCUU 1852
X CGAA AGGCUCAG ACUUUGGG
1557 CCCCAAAG CUGAUGAG1152 UGAGCCUUA 1853
X CGAA AAGGCUCA CUUUGGGG
1560 CAUCCCCA CUGAUGAG1153 GCCUUACUU 1854
X CGAA AGUAAGGC UGGGGAUG
1561 CCAUCCCC CUGAUGAG1154 CCUUACUUU 1855
X CGAA AAGUAAGG GGGGAUGG
1576 UUGGAUUU CUGAUGAG1155 GGACCAAUC 1856
X CGAA AUUGGUCC AAAUCCAA
1581 GCUUCUUG CUGAUGAG1156 AAUCAAAUC 1857
X CGAA AUUUGAUU CAAGAAGC
1591 UUGUAUAG CUGAUGAG1157 AAGAAGCUU 1858
X CGAA AGCUUCUU CUAUACAA
1592 UUUGUAUA CUGAUGAG1158 AGAAGCUUC 1859
X CGAA AAGCUUCU UAUACAAA
1594 GGUUUGUA CUGAUGAG1159 AAGCUUCUA 1860
X CGAA AGAAGCUU UACAAACC
1596 CGGGUUUG CUGAUGAG1160 GCUUCUAUA 1861
X CGAA AUAGAAGC CAAACCCG
1606 UAGUGAUU CUGAUGAG1161 AAACCCGUU 1862
X CGAA ACGGGUUU AAUCACUA
1607 AUAGUGAU CUGAUGAG1162 AACCCGUUA 1863
X CGAA AACGGGUU AUCACUAU
1610 CUCAUAGU CUGAUGAG1163 CCGUUAAUC 1869
X CGAA AUUAACGG ACUAUGAG
1614 AAGCCUCA CUGAUGAG1164 UAAUCACUA 1865
X CGAA AGUGAUUA UGAGGCUU
1622 AUGUUGCC CUGAUGAG1165 AUGAGGCUU 1866
X CGAA AGCCUCAU GGCAACAU
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Seq. I.p. Seq. I.D.
Position RZ No. Substrate No.
1631 CACUUGAA CUGAUGAG1166 GGCAACAUA 1867
X CGAA AUGUUGCC UUCAAGUG
1633 GUCACUUG CUGAUGAG1167 CAACAUAUU 1868
X CGAA AUAUGUUG CAAGUGAC
1634 UGUCACUU CUGAUGAG1168 AACAUAUUC 1869
X CGAA AAUAUGUU AAGUGACA
1651 AGUGUAAC CUGAUGAG1169 AAUGAGAUU 1870
X CGAA AUCUCAUU GUUACACU
1654 UUGAGUGU CUGAUGAG1170 GAGAUUGUU 1871
X CGAA ACAAUCUC ACACUCAA
1655 GUUGAGUG CUGAUGAG1171 AGAUUGUUA 1872
X CGAA AACAAUCU CACUCAAC
1660 AAAUAGUU CUGAUGAG1172 GUUACACUC 1873
X CGAA AGUGUAAC AACUAUUU
1665 GUUCCAAA CUGAUGAG1173 ACUCAACUA 1874
X CGAA AGUUGAGU UUUGGAAC
1667 AGGUUCCA CUGAUGAG1179 UCAACUAUU 1875
X CGAA AUAGUUGA UGGAACCU
1668 GAGGUUCC CUGAUGAG1175 CAACUAUUU 1876
X CGAA AAUAGUUG GGAACCUC
1676 UUCUGUCC CUGAUGAG1176 UGGAACCUC 1877
X CGAA AGGUUCCA GGACAGAA
1686 AGAGUUCA CUGAUGAG1177 GACAGAAUA 1878
X CGAA AUUCUGUC UGAACUCU
1693 UGCACACA CUGAUGAG1178 UAUGAACUC 1879
X CGAA AGUUCAUA UGUGUGCA
1708 CCACGACG CUGAUGAG1179 CAACUGGUC 1880
X CGAA ACCAGUUG CGUCGUGG
1712 CUCUCCAC CUGAUGAG1180 UGGUCCGUC 1881
X CGAA ACGGACCA GUGGAGAG
1736 AGGUCCAG CUGAUGAG1181 AAGGGCAUC 1882
X CGAA AUGCCCUU CUGGACCU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1755 CUGUUGUG CUGAUGAG1182 GAGACGCUU 1883
X CGAA AGCGUCUC CACAACAG
1756 GCUGUUGU CUGAUGAG1183 AGACGCUUC 1884
X CGAA AAGCGUCU ACAACAGC
1766 UCCGAUAG CUGAUGAG1184 CAACAGCUU 1885
X CGAA AGCUGUUG CUAUCGGA
1767 GUCGGAUA CUGAUGAG1185 AACAGCUUC 1886
X CGAA AAGCUGUU UAUCGGAC
1769 GAGUCCGA CUGAUGAG1186 CAGCUUCUA 1887
X CGAA AGAAGCUG UCGGACUC
1771 GGGAGUCC CUGAUGAG1187 GCUUCUAUC 1888
X CGAA AUAGAAGC GGACUCCC
1777 GGAGGAGG CUGAUGAG1188 AUCGGACUC 1889
X CGAA AGUCCGAU, CCUCCUCC
1781 UCUUGGAG CUGAUGAG1189 GACUCCCUC 1890
X CGAA AGGGAGUC CUCCAAGA
1784 ACCUCUUG CUGAUGAG1190 UCCCUCCUC 1891
2 O X CGAA AGGAGGGA CAAGAGGU
1793 GAGAUUUA CUGAUGAG1191 CAAGAGGUC 1892
X CGAA ACCUCUUG UAAAUCUC
1795 AGGAGAUU CUGAUGAG1192 AGAGGUCUA 1893
X CGAA AGACCUCU AAUCUCCU
2 5
1799 AGGCAGGA CUGAUGAG1193 GUCUAAAUC 1894
X CGAA AUUUAGAC UCCUGCCU
1801 UUAGGCAG CUGAUGAG1194 CUAAAUCUC 1895
X CGAA AGAUUUAG CUGCCUAA
1808 CUGACUUU CUGAUGAG1195 UCCUGCCUA 1896
30
X CGAA AGGCAGGA AAAGUCAG
1814 AGUGGUCU CUGAUGAG1196 CUAAAAGUC 1897
X CGAA ACUUUUAG AGACCACU
1823 CAAAUUUA CUGAUGAG1197 AGACCACUC 1898
X CGAA AGUGGUCU UAAAUUUG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1825 GUCAAAUU CUGAUGAG1198 ACCACUCUA 1899
X CGAA AGAGUGGU AAUUUGAC
1829 CCAGGUCA CUGAUGAG1199 CUCUAAAUU 1900
X CGAA AUUUAGAG UGACCUGG
1830 GCCAGGUC CUGAUGAG1200 UCUAAAUUU 1901
X CGAA AAUUUAGA GACCUGGC
1846 CUUGGAAA CUGAUGAG1201 CAACCAAUA 1902
X CGAA AUUGGUUG UUUCCAAG
1898 AGCUUGGA CUGAUGAG1202 ACCAAUAUU 1903
X CGAA AUAUUGGU UCCAAGCU
1899 GAGCUUGG CUGAUGAG1203 CCAAUAUUU 1904
X CGAA AAUAUUGG CCAAGCUC
1850 CGAGCUUG CUGAUGAG1204 CAAUAUUUC 1905
X CGAA AAAUAUUG CAAGCUCG
1857 CAUCUUCC CUGAUGAG1205 UGCAAGCUC 1906
X CGAA AGCUUGGA GGAAGAUG
1869 CAACAUAA CUGAUGAG1206 AGAUGACUU 1907
X CGAA AGUCAUCU UUAUGUUG
1870 UCAACAUA CUGAUGAG1207 GAUGACUUU 1908
X CGAA AAGUCAUC UAUGUUGA
1871 UUCAACAU CUGAUGAG1208 AUGACUUUU 1909
X CGAA AAAGUCAU AUGUUGAA
18?2 CUUCAACA CUGAUGAG1209 UGACUUUUA 1910
X CGAA AAAAGUCA UGUUGAAG
1876 UCCACUUC CUGAUGAG1210 UUUUAUGUU 1911
X CGAA ACAUAAAA GAAGUGGA
1893 UUUGCACA CUGAUGAG1211 GAGAAGGUC 1912
X CGAA ACCUUCUC UGUGCAAA
1910 AUUCUGCU CUGAUGAG1212 AAAGUGAUC 1913
X CGAA AUCACUUU AGCAGAAU
1919 AACUUUAA CUGAUGAG1213 AGCAGAAUA 1914
X CGAA AUUCUGCU UUAAAGUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1921 GGAACUUU CUGAUGAG1214 CAGAAUAUU 1915
X CGAA AUAUUCUG AAAGUUCC
1922 UGGAACUU CUGAUGAG1215 AGAAUAUUA 1916
X CGAA AAUAUUCU AAGUUCCA
1927 UUGCCUGG CUGAUGAG1216 AUUAAAGUU 1917
X CGAA ACUUUAAU CCAGGCAA
1928 GUUGCCUG CUGAUGAG1217 UUAAAGUUC 1918
X CGAA AACUUUAA CAGGCAAC
1938 CCGAAGUC CUGAUGAG1218 ' AGGCAACUU 1919
X CGAA AGUUGCCU GACUUCGG
1943 UAGCACCG CUGAUGAG1219 ACUUGACUU 1920
X CGAA AGUCAAGU CGGUGCUA
1944 GUAGCACC CUGAUGAG1220 CUUGACUUC 1921
X CGAA AAGUCAAG GGUGCUAC
1951 UUGUUAAG CUGAUGAG1221 UCGGUGCUA 1922
X CGAA AGCACCGA CUUAACAA
1954 AAGUUGUU CUGAUGAG1222 GUGCUACUU 1923
2 O X CGAA AGUAGCAC AACAACUU
1955 UAAGUUGU CUGAUGAG1223 UGCUACUUA 1924
X CGAA AAGUAGCA ACAACUUA
1962 UGGGAUGU CUGAUGAG1224 UAACAACUU 1925
X CGAA AGUUGUUA ACAUCCCA
1963 CUGGGAUG CUGAUGAG1225 AACAACUUA 1926
X CGAA AAGUUGUU CAUCCCAG
1967 CUCCCUGG CUGAUGAG1226 ACUUACAUC 1927
X CGAA AUGUAAGU CCAGGGAG
1980 GGACCACG CUGAUGAG1227 GGAGCAGUA 1928
X CGAA ACUGCUCC CGUGGUCC
1987 CUAGCUCG CUGAUGAG1228 UACGUGGUC 1929
X CGAA ACCACGUA CGAGCUAG
1999 GUUGACUC CUGAUGAG1229 UCCGAGCUA 1930
X CGAA AGCUCGGA GAGUCAAC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1999 UUGGUGUU CUGAUGAG1230 GCUAGAGUC 1931
X CGAA ACUCUAGC AACACCAA
2033 AGCAGUGA CUGAUGAG1231 GUGAAGAUC 1932
X CGAA AUCUUCAC UCACUGCU
2035 CAAGCAGU CUGAUGAG1232 GAAGAUCUC 1933
X CGAA AGAUCUUC ACUGCUUG
2042 AAGGGUCC CUGAUGAG1233 UCACUGCUU 1939
1Q X CGAA AGCAGUGA GGACCCUU
2050 AUGUCACU CUGAUGAG1234 UGGACCCUU 1935
X CGAA AGGGUCCA AGUGACAU
2051 AAUGUCAC CUGAUGAG1235 GGACCCUUA 1936
X CGAA AAGGGUCC GUGACAUU
2059 GGAGGAAG CUGAUGAG1236 AGUGACAUU 1937
X CGAA AUGUCACU CUUCCUCC
2060 AGGAGGAA CUGAUGAG1237 GUGACAUUC 1938
X CGAA AAUGUCAC UUCCUCCU
2062 UGAGGAGG CUGAUGAG1238 GACAUUCUU 1939
X CGAA AGAAUGUC CCUCCUCA
2063 UUGAGGAG CUGAUGAG1239 ACAUUCUUC 1940
X CGAA AAGAAUGU CUCCUCAA
2066 UGGUUGAG CUGAUGAG1290 UUCUUCCUC 1941
X CGAA AGGAAGAA CUCAACCA
2069 UUCUGGUU CUGAUGAG1291 UUCCUCCUC 1942
X CGAA AGGAGGAA AACCAGAA
2083 GAAAUCUU CUGAUGAG1242 GAAAACAUC 1943
X CGAA AUGUUUUC AAGAUUUC
2089 AUGUUGGA CUGAUGAG1243 AUCAAGAUU 1944
X CGAA AUCUUGAU UCCAACAU
2090 AAUGUUGG CUGAUGAG1249 UCAAGAUUU 1945
X CGAA AAUCUUGA CCAACAUU
2091 UAAUGUUG CUGAUGAG1295 CAAGAUUUC 1946
X CGAA AAAUCUUG CAACAUUA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2098 GAGUGUGU CUGAUGAG1246 UCCAACAUU 1947
X CGAA AUGUUGGA ACACACUC
2099 GGAGUGUG CUGAUGAG1247 CCAACAUUA 1948
X CGAA AAUGUUGG CACACUCC
2106 CAGCCGAG CUGAUGAG1298 UACACACUC 1949
X CGAA AGUGUGUA CUCGGCUG
2109 UCACAGCC CUGAUGAG1299 ACACUCCUC 1950
X CGAA AGGAGUGU GGCUGUGA
2119 GUCCAAGA CUGAUGAG1250 GCUGUGAUU 1951
X CGAA AUCACAGC UCUUGGAC
2120 UGUCCAAG CUGAUGAG1251 CUGUGAUUU 1952
X CGAA AAUCACAG CUUGGACA
2121 UUGUCCAA CUGAUGAG1252 UGUGAUUUC 1953
X CGAA AAAUCACA UUGGACAA
2123 UAUUGUCC CUGAUGAG1253 UGAUUUCUU 1954
X CGAA AGAAAUCA GGACAAUA
2131 CCAUCCAA CUGAUGAG1254 UGGACAAUA 1955
X CGAA AUUGUCCA UUGGAUGG
2133 AGCCAUCC CUGAUGAG1255 GACAAUAUU 1956
X CGAA AUAUUGUC GGAUGGCU
2142 AAAUAGAA CUGAUGAG1256 GGAUGGCUA 1957
X CGAA AGCCAUCC UUCUAUUU
2144 AGAAAUAG CUGAUGAG1257 AUGGCUAUU 1958
X CGAA AUAGCCAU CUAUUUCU
2195 AAGAAAUA CUGAUGAG1258 UGGCUAUUC 1959
X CGAA AAUAGCCA UAUUUCUU
2197 AGAAGAAA CUGAUGAG1259 GCUAUUCUA 1960
X CGAA AGAAUAGC UUUCUUCU
2149 AUAGAAGA CUGAUGAG1260 UAUUCUAUU 1961
X CGAA AUAGAAUA UCUUCUAU
2150 AAUAGAAG CUGAUGAG1261 AUUCUAUUU 1962
X CGAA AAUAGAAU CUUCUAUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2151 UAAUAGAA CUGAUGAG1262 UUCUAUUUC 1963
X CGAA AAAUAGAA UUCUAUUA
2153 AGUAAUAG CUGAUGAG1263 CUAUUUCUU 1969
X CGAA AGAAAUAG CUAUUACU
2159 UAGUAAUA CUGAUGAG1264 UAUUUCUUC 1965
X CGAA AAGAAAUA UAUUACUA
2156 GAUAGUAA CUGAUGAG1265 UUUCUUCUA 1966
X CGAA AGAAGAAA UUACUAUC
2158 CGGAUAGU CUGAUGAG1266 UCUUCUAUU 1967
X CGAA AUAGAAGA ACUAUCCG
2159 ACGGAUAG CUGAUGAG1267 CUUCUAUUA 1968
X CGAA AAUAGAAG CUAUCCGU
2162 GUAACGGA CUGAUGAG1268 CUAUUACUA 1969
X CGAA AGUAAUAG UCCGUUAC
2164 UUGUAACG CUGAUGAG1269 AUUACUAUC 1970
X CGAA AUAGUAAU CGUUACAA
2168 AACCUUGU CUGAUGAG1270 CUAUCCGUU 1971
2 O X CGAA ACGGAUAG ACAAGGUU
2169 GAACCUUG CUGAUGAG1271 UAUCCGUUA 1972
X CGAA AACGGAUA CAAGGUUC
2176 UUGCCUUG CUGAUGAG1272 UACAAGGUU 1973
X CGAA ACCUUGUA CAAGGCAA
2177 CUUGCCUU CUGAUGAG1273 ACAAGGUUC 1974
X CGAA AACCUUGU AAGGCAAG
2203 UUCACAUC CUGAUGAG1274 GAGCACGUU 1975
X CGAA ACGUGCUG GAUGUGAA
2215 GCAUUCUU CUGAUGAG1275 GUGAAGAUA 1976
X CGAA AUCUUCAC AAGAAUGC
2230 UACUGAAU CUGAUGAG1276 GCCACCAUC 1977
X CGAA AUGGUGGC AUUCAGUA
2233 UGAUACUG CUGAUGAG1277 ACCAUCAUU 1978
X CGAA AUGAUGGU CAGUAUCA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2234 CUGAUACU CUGAUGAG1278 CCAUCAUUC 1979
X CGAA AAUGAUGG AGUAUCAG
2238 UGAGCUGA CUGAUGAG1279 CAUUCAGUA 1980
X CGAA ACUGAAUG UCAGCUCA
2240 CUUGAGCU CUGAUGAG1280 UUCAGUAUC 1981
X CGAA AUACUGAA AGCUCAAG
2295 AGGCCCUU CUGAUGAG1281 UAUCAGCUC 1982
X CGAA AGCUGAUA AAGGGCCU
2259 UCAGGCUC CUGAUGAG1282 AAGGGCCUA 1983
X CGAA AGGCCCUU GAGCCUGA
2271 CCACCUGG CUGAUGAG1283 AACAGCAUA 1984
X CGAA AUGCUGUU CCAGGUGG
2284 UCUGCAAA CUGAUGAG1289 GUGGACAUU 1985
X CGAA AUGUCCAC UUUGCAGA
2285 CUCUGCAA CUGAUGAG1285 UGGACAUUU 1986
X CGAA AAUGUCCA UUGCAGAG
2286 UCUCUGCA CUGAUGAG1286 GGACAUUUU 1987
2 O X CGAA AAAUGUCC UGCAGAGA
2287 UUCUCUGC CUGAUGAG1287 GACAUUUUU 1988
X CGAA AAAAUGUC GCAGAGAA
2302 CUUGACCC CUGAUGAG1288 AACAACAUA 1989
X CGAA AUGUUGUU GGGUCAAG
2307 GGUUGCUU CUGAUGAG1289 CAUAGGGUC 1990
X CGAA ACCCUAUG AAGCAACC
2322 CAUGAGAA CUGAUGAG1290 CCCAGCCUU 1991
X CGAA AGGCUGGG UUCUCAUG
2323 UCAUGAGA CUGAUGAG1291 CCAGCCUUU 1992
X CGAA AAGGCUGG UCUCAUGA
2329 UUCAUGAG CUGAUGAG1292 CAGCCUUUU 1993
X CGAA AAAGGCUG CUCAUGAA
2325 GUUCAUGA CUGAUGAG1293 AGCCUUUUC 1994
X CGAA AAAAGGCU UCAUGAAC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2327 CAGUUCAU CUGAUGAG1294 CCUUUUCUC 1995
X CGAA AGAAAAGG AUGAACUG
2344 GAUUCUGG CUGAUGAG1295 GUGACCCUC 1996
X CGAA AGGGUCAC CCAGAAUC
2352 GUGCUUGA CUGAUGAG1296 CCCAGAAUC 1997
X CGAA AUUCUGGG UCAAGCAC
2354 UGGUGCUU CUGAUGAG1297 CAGAAUCUC 1998
X CGAA AGAUUCUG AAGCACCA
2371 CCCCCUCC CUGAUGAG1298 GCGGACCUC 1999
X CGAA AGGUCCGC GGAGGGGG
2392 AUGGCUAU CUGAUGAG1299 AUGCUGCUU 2000
X CGAA AGCAGCAU AUAGCCAU
2393 GAUGGCUA CUGAUGAG1300 UGCUGCUUA 2001
X CGAA AAGCAGCA UAGCCAUC
2395 AGGAUGGC CUGAUGAG1301 CUGCUUAUA 2002
X CGAA AUAAGCAG GCCAUCCU
2901 GAGCCAAG CUGAUGAG1302 AUAGCCAUC 2003
X CGAA AUGGCUAU CUUGGCUC
2904 GCAGAGCC CUGAUGAG1303 GCCAUCCUU 2009
X CGAA AGGAUGGC GGCUCUGC
2409 UUCCAGCA CUGAUGAG1304 CCUUGGCUC 2005
X CGAA AGCCAAGG UGCUGGAA
2439 GAAAGGCC CUGAUGAG1305 UGUGCUGUU 2006
X CGAA ACAGCACA GGCCUUUC
2445 UGAUCAGA CUGAUGAG1306 GUUGGCCUU 2007
X CGAA AGGCCAAC UCUGAUCA
2446 AUGAUCAG CUGAUGAG1307 UUGGCCUUU 2008
X CGAA AAGGCCAA CUGAUCAU
2447 UAUGAUCA CUGAUGAG1308 UGGCCUUUC 2009
X CGAA AAAGGCCA UGAUCAUA
2952 UGCAAUAU CUGAUGAG1309 UUUCUGAUC 2010
X CGAA AUCAGAAA AUAUUGCA
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Seq. I.D. Seq. I.D.
Position R2 No. Substrate No.
2455 AAUUGCAA CUGAUGAG1310 CUGAUCAUA 2011
X CGAA AUGAUCAG UUGCAAUU
2457 UCAAUUGC CUGAUGAG1311 GAUCAUAUU 2012
X CGAA AUAUGAUC GCAAUUGA
2463 CCCUCUUC CUGAUGAG1312 AUUGCAAUU 2013
X CGAA AUUGCAAU GAAGAGGG
2502 CGUUUUGG CUGAUGAG1313 CCAAGCCUU 2014
X CGAA AGGCUUGG CCAAAACG
2503 ACGUUUUG CUGAUGAG1314 CAAGCCUUC 2015
X CGAA AAGGCUUG CAAAACGU
2535 CUGAGUUG CUGAUGAG1315 UGUGCAGUU 2016
X CGAA ACUGCACA CAACUCAG
2536 CCUGAGUU CUGAUGAG1316 GUGCAGUUC 2017
X CGAA AACUGCAC AACUCAGG
2541 GAGUCCCU CUGAUGAG1317 GUUCAACUC 2018
X CGAA AGUUGAAC AGGGACUC
2549 UAGGGCCA CUGAUGAG1318 CAGGGACUC 2019
X CGAA AGUCCCUG UGGCCCUA
2557 UUCCUGUU CUGAUGAG1319 CUGGCCCUA 2020
X CGAA AGGGCCAG AACAGGAA
2569 UUGUUUUU CUGAUGAG1320 AGGAAGGUC 2021
X CGAA ACCUUCCU AAAAACAA
2585 AAUUGUAG CUGAUGAG1321 ACCCAGAUC 2022
X CGAA AUCUGGGU CUACAAUU
2588 AUAAAUUG CUGAUGAG1322 CAGAUCCUA 2023
X CGAA AGGAUCUG CAAUUUAU
2593 ACUGGAUA CUGAUGAG1323 CCUACAAUU 2029
X CGAA AUUGUAGG UAUCCAGU
2594 CACUGGAU CUGAUGAG1329 CUACAAUUU 2025
X CGAA AAUUGUAG AUCCAGUG
2595 GCACUGGA CUGAUGAG1325 UACAAUUUA 2026
X CGAA AAAUUGUA UCCAGUGC
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Seq. I.D. Seq. I.D.
Position R2 No. Substrate No.
2597 AAGCACUG CUGAUGAG1326 CAAUUUAUC 2027
X CGAA AUAAAUUG CAGUGCUU
2605 UUCCAGUC CUGAUGAG1327 CCAGUGCUU 2028
X CGAA AGCACUGG GACUGGAA
2620 UGAAAUUU CUGAUGAG1328 AAUGACAUC 2029
X CGAA AUGUCAUU AAAUUUCA
2625 CAUCUUGA CUGAUGAG1329 CAUCAAAUU 2030
lO X CGAA AUUUGAUG UCAAGAUG
2626 ACAUCUUG CUGAUGAG1330 AUCAAAUUU 2031
X CGAA AAUUUGAU CAAGAUGU
2627 CACAUCUU CUGAUGAG1331 UCAAAUUUC 2032
X CGAA AAAUUUGA AAGAUGUG
2638 CCCUCCCC CUGAUGAG1332 GAUGUGAUU 2033
X CGAA AUCACAUC GGGGAGGG
2651 UUGGCCAA CUGAUGAG1333 AGGGCAAUU 2034
X CGAA AUUGCCCU UUGGCCAA
2652 CUUGGCCA CUGAUGAG1339 GGGCAAUUU 2035
2 O X CGAA AAUUGCCC UGGCCAAG
2653 ACUUGGCC CUGAUGAG1335 GGCAAUUUU 2036
X CGAA AAAUUGCC GGCCAAGU
2662 GCCUUAAG CUGAUGAG1336 GGCCAAGUU 2037
X CGAA ACUUGGCC CUUAAGGC
2 5
2663 CGCCUUAA CUGAUGAG1337 GCCAAGUUC 2038
X CGAA AACUUGGC UUAAGGCG
2665 CGCGCCUU CUGAUGAG1338 CAAGUUCUU 2039
X CGAA AGAACUUG AAGGCGCG
2666 GCGCGCCU CUGAUGAG1339 AAGUUCUUA 2040
30
X CGAA AAGAACUU AGGCGCGC
2677 UCCUUCUU CUGAUGAG1340 GCGCGCAUC 2041
X CGAA AUGCGCGC AAGAAGGA
2691 CCAUCCGU CUGAUGAG1391 GGAUGGGUU 2042
X CGAA ACCCAUCC ACGGAUGG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2692 UCCAUCCG CUGAUGAG1342 GAUGGGUUA 2043
X CGAA AACCCAUC CGGAUGGA
2710 AUUCUUUU CUGAUGAG1343 GCUGCCAUC 2049
X CGAA AUGGCAGC AAAAGAAU
2727 UGGAGGCA CUGAUGAG1399 GAAAGAAUA 2095
X CGAA AUUCUUUC UGCCUCCA
2733 CAUCUUUG CUGAUGAG1345 AUAUGCCUC 2046
X CGAA AGGCAUAU CAAAGAUG
2749 GUCCCUGU CUGAUGAG1346 AAGAUGAUC 2047
X CGAA AUCAUCUU ACAGGGAC
2754 CUCCUGGA CUGAUGAG1397 CAGGGACUU 2098
X CGAA AGUCCCUG UGCAGGAG
2755 UCUCCUGC CUGAUGAG1348 AGGGACUUU 2049
X CGAA AAGUCCCU GCAGGAGA
2773 UUACAAAG CUGAUGAG1349 CUGGAAGUU 2050
X CGAA ACUUCCAG CUUUGUAA
2779 UUUACAAA CUGAUGAG1350 UGGAAGUUC 2051
2 O X CGAA AACUUCCA UUUGUAAA
2776 AGUUUACA CUGAUGAG1351 GAAGUUCUU 2052
X CGAA AGAACUUC UGUAAACU
2777 AAGUUUAC CUGAUGAG1352 AAGUUCUUU 2053
X CGAA AAGAACUU GUAAACUU
2780 UCCAAGUU CUGAUGAG1353 UUCUUUGUA 2054
X CGAA ACAAAGAA AACUUGGA
2785 UGGUGUCC CUGAUGAG1354 UGUAAACUU 2055
X CGAA AGUUUACA GGACACCA
2795 GAUGUUUG CUGAUGAG1355 GACACCAUC 2056
X CGAA AUGGUGUC CAAACAUC
2803 AGAUUGAU CUGAUGAG13,56 CCAAACAUC 2057
X CGAA AUGUUUGG AUCAAUCU
2806 AAGAGAUU CUGAUGAG1357 AACAUCAUC 2058
X CGAA AUGAUGUU AAUCUCUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2810 UCCUAAGA CUGAUGAG1358 UCAUCAAUC 2059
X CGAA AUUGAUGA UCUUAGGA
2812 GCUCCUAA CUGAUGAG1359 AUCAAUCUC 2060
X CGAA AGAUUGAU UUAGGAGC
2814 AUGCUCCU CUGAUGAG1360 CAAUCUCUU 2061
X CGAA AGAGAUUG AGGAGCAU
2815 CAUGCUCC CUGAUGAG1361 AAUCUCUUA 2062
X CGAA AAGAGAUU GGAGCAUG
2831 GUAGCCUC CUGAUGAG1362 GUGAACAUC 2063
X CGAA AUGUUCAC GAGGCUAC
2838 GGUACAAG CUGAUGAG1363 UCGAGGCUA 2064
X CGAA AGCCUCGA CUUGUACC
2841 CCAGGUAC CUGAUGAG1364 AGGCUACUU 2065
X CGAA AGUAGCCU GUACCUGG
2844 UGGCCAGG CUGAUGAG1365 CUACUUGUA 2066
X CGAA ACAAGUAG CCUGGCCA
2854 GCGUACUC CUGAUGAG1366 CUGGCCAUU 2067
2 O X CGAA AUGGCCAG GAGUACGC
2859 GGGGCGCG CUGAUGAG1367 CAUUGAGUA 2068
X CGAA ACUCAAUG CGCGCCCC
2878 AAGUCCAG CUGAUGAG1368 GGAAACCUU 2069
X CGAA AGGUUUCC CUGGACUU
2879 GAAGUCCA CUGAUGAG1369 GAAACCUUC 2070
X CGAA AAGGUUUC UGGACUUC
2886 UGCGAAGG CUGAUGAG1370 UCUGGACUU 2071
X CGAA AGUCCAGA CCUUCGCA
2887 UUGCGAAG CUGAUGAG1371 CUGGACUUC 2072
X CGAA AAGUCCAG CUUCGCAA
2890 CUCUUGCG CUGAUGAG1372 GACUUCCUU 2073
X CGAA AGGAAGUC CGCAAGAG
2891 GCUCUUGC CUGAUGAG1373 ACUUCCUUC 2074
X CGAA AAGGAAGU GCAAGAGC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2925 CAAUGGCA CUGAUGAG1379 CCCAGCAUU 2075
X CGAA AUGCUGGG UGCCAUUG
2926 GCAAUGGC CUGAUGAG1375 CCAGCAUUU 2076
X CGAA AAUGCUGG GCCAUUGC
2932 CUAUUGGC CUGAUGAG1376 UUUGCCAUU 2077
X CGAA AUGGCAAA GCCAAUAG
2939 CGCGGUGC CUGAUGAG1377 UUGCCAAUA 2078
X CGAA AUUGGCAA GCACCGCG
2949 ACAGUGUG CUGAUGAG1378 CACCGCGUC 2079
X CGAA ACGCGGUG CACACUGU
2958 GCUGGGAG CUGAUGAG1379 CACACUGUC 2080
X CGAA ACAGUGUG CUCCCAGC
2961 GCUGCUGG CUGAUGAG1380 ACUGUCCUC 2087.
X CGAA AGGACAGU CCAGCAGC
2971 AAGUGAAG CUGAUGAG1381 CAGCAGCUC 2082
X CGAA AGCUGCUG CUUCACUU
2974 GCGAAGUG CUGAUGAG1382 CAGCUCCUU 2083
2 O X CGAA AGGAGCUG CACUUCGC
2975 AGCGAAGU CUGAUGAG1383 AGCUCCUUC 2084
X CGAA AAGGAGCU ACUUCGCU
2979 CGGCAGCG CUGAUGAG1384 CCUUCACUU 2085
X CGAA AGUGAAGG CGCUGCCG
2980 UCGGCAGC CUGAUGAG1385 CUUCACUUC 2086
X CGAA AAGUGAAG GCUGCCGA
3009 GGCUCAAG CUGAUGAG1386 CAUGGACUA 2087
X CGAA AGUCCAUG CUUGAGCC
3012 UUUGGCUC CUGAUGAG1387 GGACUACUU 2088
~
X CGAA AGUAGUCC GAGCCAAA
3027 UGUGGAUA CUGAUGAG1388 AAAACAGUU 2089
X CGAA ACUGUUUU UAUCCACA
3028 CUGUGGAU CUGAUGAG1389 AAACAGUUU 2090
X CGAA AACUGUUU AUCCACAG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3029 CCUGUGGA CUGAUGAG1390 AACAGUUUA 2091
X CGAA AAACUGUU UCCACAGG
3031 UCCCUGUG CUGAUGAG1391 CAGUUUAUC 2092
X CGAA AUAAACUG CACAGGGA
3041 GGCAGCCA CUGAUGAG1392 ACAGGGAUC 2093
X CGAA AUCCCUGU UGGCUGCC
3058 CCAACUAA CUGAUGAG1393 AGAAACAUU 2094
X CGAA AUGUUUCU UUAGUUGG
3059 ACCAACUA CUGAUGAG1394 GAAACAUUU 2095
X CGAA AAUGUUUC UAGUUGGU
3060 CACCAACU CUGAUGAG1395 AAACAUUUU 2096
X CGAA AAAUGUUU AGUUGGUG
3061 UCACCAAC CUGAUGAG1396 AACAUUUUA 2097
X CGAA AAAAUGUU GUUGGUGA
3064 UUUUCACC CUGAUGAG1397 AUUUUAGUU 2098
X CGAA ACUAAAAU GGUGAAAA
3075 UUGCCACA CUGAUGAG1398 UGAAAACUA 2099
2 O X CGAA AGUUUUCA UGUGGCAA
3088 AAAUCUGC CUGAUGAG1399 GCAAAAAUA 2100
X CGAA AUUUUUGC GCAGAUUU
3095 CAAUCCAA CUGAUGAG1400 UAGCAGAUU 2101
X CGAA AUCUGCUA UUGGAUUG
3096 ACAAUCCA CUGAUGAG1401 AGCAGAUUU 2102
X CGAA AAUCUGCU UGGAUUGU
309? GACAAUCC CUGAUGAG1902 GCAGAUUUU 2103
X CGAA AAAUCUGC GGAUUGUC
3102 CUCGGGAC CUGAUGAG1403 UUUUGGAUU 2104
X CGAA AUCCAAAA GUCCCGAG
3105 GACCUCGG CUGAUGAG1904 UGGAUUGUC 2105
X CGAA ACAAUCCA CCGAGGUC
3113 CACCUCUU CUGAUGAG1405 CCCGAGGUC 2106
X CGAA ACCUCGGG AAGAGGUG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3123 UUUUCACG CUGAUGAG1406 AGAGGUGUA 2107
X CGAA ACACCUCU CGUGAAAA
3148 CGCACUGG CUGAUGAG1407 GGAAGGCUC 2108
X CGAA AGCCUUCC CCAGUGCG
3169 AGUGACUC CUGAUGAG1408 AUGGCCAUC 2109
X CGAA AUGGCCAU GAGUCACU
3174 AAUUCAGU CUGAUGAG1909 CAUCGAGUC 2110
X CGAA ACUCGAUG ACUGAAUU
3182 CACACUGU CUGAUGAG1410 CACUGAAUU 2111
X CGAA AUUCAGUG ACAGUGUG
3183 ACACACUG CUGAUGAG1411 ACUGAAUUA 2112
X CGAA AAUUCAGU CAGUGUGU
3192 UGGUUGUG CUGAUGAG1412 CAGUGUGUA 2113
X CGAA ACACACUG CACAACCA
3211 UAGGACCA CUGAUGAG1913 AGUGAUGUA 2119
X CGAA ACAUCACU UGGUCCUA
3216 CACCAUAG CUGAUGAG1914 UGUAUGGUC 2115
X CGAA ACCAUACA CUAUGGUG
3219 ACACACCA CUGAUGAG1415 AUGGUCCUA 2116
X CGAA AGGACCAU UGGUGUGU
3228 CCCAUAGU CUGAUGAG1416 UGGUGUGUU 2117
X CGAA ACACACCA ACUAUGGG
2 5
3229 UCCCAUAG CUGAUGAG1417 GGUGUGUUA 2118
X CGAA AACACACC CUAUGGGA
3232 AUCUCCCA CUGAUGAG1418 GUGUUACUA 2119
X CGAA AGUAACAC UGGGAGAU
3241 AAGCUAAC CUGAUGAG1419 UGGGAGAUU 2120
X CGAA AUCUCCCA GUUAGCUU
3244 CCUAAGCU CUGAUGAG1920 GAGAUUGUU 2121
X CGAA ACAAUCUC AGCUUAGG
3245 UCCUAAGC CUGAUGAG1421 AGAUUGUUA 2122
X CGAA AACAAUCU GCUUAGGA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3249 UGCCUCCU CUGAUGAG1422 UGUUAGCUU 2123
X CGAA AGCUAACA AGGAGGCA
3250 GUGCCUCC CUGAUGAG1423 GUUAGCUUA 2124
X CGAA AAGCUAAC GGAGGCAC
3269 UCCCGCAG CUGAUGAG1424 CACACCCUA 2125
X CGAA AGGGUGUG CUGCGGGA
3278 UUCUGCAC CUGAUGAG1425 GGAUGACUU 2126
X CGAA AGUCAUCC GUGCAGAA
3289 UUCUCGUA CUGAUGAG1426 GCAGAACUC 2127
X CGAA AGUUCUGC UACGAGAA
3291 GCUUCUCG CUGAUGAG1927 AGAACUCUA 2128
X CGAA AGAGUUCU CGAGAAGC
3312 CCAGUCUG CUGAUGAG1428 CCAGGGCUA 2129
X CGAA AGCCCUGG CAGACUGG
3351 UUAGAUCA CUGAUGAG1429 UGAGGUGUA 2130
X CGAA ACACCUCA UGAUCUAA
3356 UCUCAUUA CUGAUGAG1430 UGUAUGAUC 2131
X CGAA AUCAUACA UAAUGAGA
3358 UGUCUCAU CUGAUGAG1931 UAUGAUCUA 2132
X CGAA AGAUCAUA AUGAGACA
3386 CCUCUCAU CUGAUGAG1432 AGAAGCCUU 2133
X CGAA AGGCUUCU AUGAGAGG
3387 GCCUCUCA CUGAUGAG1433 GAAGCCUUA 2134
X CGAA AAGGCUUC UGAGAGGC
3399 GGGCAAAU CUGAUGAG1434 GAGGCCAUC 2135
X CGAA AUGGCCUC AUUUGCCC
3402 UCUGGGCA CUGAUGAG1935 GCCAUCAUU 2136
X CGAA AUGAUGGC UGCCCAGA
3403 AUCUGGGC CUGAUGAG1436 CCAUCAUUU 2137
X CGAA AAUGAUGG GCCCAGAU
3912 GACACCAA CUGAUGAG1937 GCCCAGAUA 2138
X CGAA AUCUGGGC UUGGUGUC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3419 AGGACACC CUGAUGAG1438 CCAGAUAUU 2139
X CGAA AUAUCUGG GGUGUCCU
3920 UGUUUAAG CUGAUGAG1939 AUUGGUGUC 2140
X CGAA ACACCAAU CUUAAACA
3923 UUCUGUUU CUGAUGAG1440 GGUGUCCUU 2141
X CGAA AGGACACC AAACAGAA
3429 AUUCUGUU CUGAUGAG1441 GUGUCCUUA 2142
X CGAA AAGGACAC AACAGAAU
3435 GCUCCUCU CUGAUGAG1942 CAGAAUGUU 2143
X CGAA ACAUUCUG AGAGGAGC
3436 CGCUCCUC CUGAUGAG1443 AGAAUGUUA 2144
X CGAA AACAUUCU GAGGAGCG
3453 UAUUCACG CUGAUGAG1449 AAAGACCUA 2145
X CGAA AGGUCUUU CGUGAAUA
3961 AAGCGUGG CUGAUGAG1445 ACGUGAAUA 2146
X CGAA AUUCACGU CCACGCUU
3969 UUCUCAUA CUGAUGAG1446 ACCACGCUU 2147
X CGAA AGCGUGGU UAUGAGAA
3470 CUUCUCAU CUGAUGAG1447 CCACGCUUU 2148
X CGAA AAGCGUGG AUGAGAAG
3471 ACUUCUCA CUGAUGAG1998 CACGCUUUA 2149
X CGAA AAAGCGUG UGAGAAGU
3480 CAUAAGUA CUGAUGAG1449 UGAGAAGUU 2150
X CGAA ACUUCUCA UACUUAUG
3481 GCAUAAGU CUGAUGAG1450 GAGAAGUUU 2151
X CGAA AACUUCUC ACUUAUGC
3482 UGCAUAAG CUGAUGAG1451 AGAAGUUUA 2152
X CGAA AAACUUCU CUUAUGCA
3985 UCCUGCAU CUGAUGAG1452 AGUUUACUU 2153
X CGAA AGUAAACU AUGCAGGA
3986 UUCCUGCA CUGAUGAG1453 GUUUACUUA 2154
X CGAA AAGUAAAC UGCAGGAA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3496 GAACAGUC CUGAUGAG1954 GCAGGAAUU 2155
X CGAA AUUCCUGC GACUGUUC
3503 UUCAGCAG CUGAUGAG1455 UUGACUGUU 2156
X CGAA ACAGUCAA CUGCUGAA
3504 CUUCAGCA CUGAUGAG1956 UGACUGUUC 2157
X CGAA AACAGUCA UGCUGAAG
3522 UUCUGUCC CUGAUGAG1457 AGCGGCCUA 2158
X CGAA AGGCCGCU GGACAGAA
3534 GGUAUACA CUGAUGAG1458 CAGAACAUC 2159
X CGAA AUGUUCUG UGUAUACC
3538 AGAGGGUA CUGAUGAG1459 ACAUCUGUA 2160
X CGAA ACAGAUGU UACCCUCU
3590 ACAGAGGG CUGAUGAG1960 AUCUGUAUA 2161
X CGAA AUACAGAU CCCUCUGU
3545 GGGAAACA CUGAUGAG1461 UAUACCCUC 2162
X CGAA AGGGUAUA UGUUUCCC
3549 GAAAGGGA CUGAUGAG1462 CCCUCUGUU 2163
X CGAA ACAGAGGG UCCCUUUC
3550 UGAAAGGG CUGAUGAG1463 CCUCUGUUU 2164
X CGAA AACAGAGG CCCUUUCA
3551 GUGAAAGG CUGAUGAG1969 CUCUGUUUC 2165
X CGAA AAACAGAG CCUUUCAC
3555 GCCAGUGA CUGAUGAG1465 GUUUCCCUU 2166
X CGAA AGGGAAAC UCACUGGC
3556 UGCCAGUG CUGAUGAG1966 UUUCCCUUU 2167
X CGAA AAGGGAAA CACUGGCA
3557 AUGCCAGU CUGAUGAG1967 UUCCCUUUC 2168
X CGAA AAAGGGAA ACUGGCAU
3576 CAGUUGUC CUGAUGAG146$ GAGACCCUU 2169
X CGAA AGGGUCUC GACAACUG
3601 CUUUGGCA CUGAUGAG1469 ACAUGCCUC 2170
X CGAA AGGCAUGU UGCCAAAG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3618 CACUUAUA CUGAUGAG1470 GAUGUGAUA 2171
X CGAA AUCACAUC UAUAAGUG
3620 UACACUUA CUGAUGAG1971 UGUGAUAUA 2172
X CGAA AUAUCACA UAAGUGUA
3622 UGUACACU CUGAUGAG1472 UGAUAUAUA 2173
X CGAA AUAUAUCA AGUGUACA
3628 CACAUAUG CUGAUGAG1973 AUAAGUGUA 2174
X CGAA ACACUUAU CAUAUGUG
3632 CCAGCACA CUGAUGAG1474 GUGUACAUA 2175
X CGAA AUGUACAC UGUGCUGG
3694 CUUGUUAG CUGAUGAG1975 GCUGGAAUU 2176
X CGAA AUUCCAGC CUAACAAG
3645 ACUUGUUA CUGAUGAG1476 CUGGAAUUC 2177
X CGAA AAUUCCAG UAACAAGU
3647 UGACUUGU CUGAUGAG1477 GGAAUUCUA 2178
X CGAA AGAAUUCC ACAAGUCA
3654 UAACCUAU CUGAUGAG1478 UAACAAGUC 2179
2 O X CGAA ACUUGUUA AUAGGUUA
3657 UAUUAACC CUGAUGAG1479 CAAGUCAUA 2180
X CGAA AUGACUUG GGUUAAUA
3661 UAAAUAUU CUGAUGAG1480 UCAUAGGUU 2181
X CGAA ACCUAUGA AAUAUUUA
3662 UUAAAUAU CUGAUGAG1981 CAUAGGUUA 2182
X CGAA AACCUAUG AUAUUUAA
3665 GUCUUAAA CUGAUGAG1482 AGGUUAAUA 2183
X CGAA AUUAACCU UUUAAGAC
3667 GUGUCUUA CUGAUGAG1983 GUUAAUAUU 2184
3 O
X CGAA AUAUUAAC UAAGACAC
3668 AGUGUCUU CUGAUGAG1484 UUAAUAUUU 2185
X CGAA AAUAUUAA AAGACACU
3669 CAGUGUCU CUGAUGAG1485 UAAUAUUUA 2186
X CGAA AAAUAUUA AGACACUG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3684 AUCACUUA CUGAUGAG1486 UGAAAAAUC 2187
X CGAA AUUUUUCA UAAGUGAU
3686 AUAUCACU CUGAUGAG1487 AAAAAUCUA 2188
X CGAA AGAUUUUU AGUGAUAU
3693 CUGAUUUA CUGAUGAG1488 UAAGUGAUA 2189
X CGAA AUCACUUA UAAAUCAG
3695 AUCUGAUU CUGAUGAG1489 AGUGAUAUA 2190
X CGAA AUAUCACU AAUCAGAU
3699 AAGAAUCU CUGAUGAG1490 AUAUAAAUC 2191
X CGAA AUUUAUAU AGAUUCUU
3704 GAGAGAAG CUGAUGAG1491 AAUCAGAUU 2192
X CGAA AUCUGAUU CUUCUCUC
3705 AGAGAGAA CUGAUGAG1492 AUCAGAUUC 2193
X CGAA AAUCUGAU UUCUCUCU
3707 UGAGAGAG CUGAUGAG1493 CAGAUUCUU 2194
X CGAA AGAAUCUG CUCUCUCA
3?08 AUGAGAGA CUGAUGAG1499 AGAUUCUUC 2195
X CGAA AAGAAUCU UCUCUCAU
3710 AAAUGAGA CUGAUGAG1495 AUUCUUCUC 2196
X CGAA AGAAGAAU UCUCAUUU
3712 UAAAAUGA CUGAUGAG1996 UCUUCUCUC 2197
X CGAA AGAGAAGA UCAUUUUA
2 5
3714 GAUAAAAU CUGAUGAG1497 UUCUCUCUC 2198
X CGAA AGAGAGAA AUUUUAUC
3717 AGGGAUAA CUGAUGAG1498 UCUCUCAUU 2199
X CGAA AUGAGAGA UUAUCCCU
3718 GAGGGAUA CUGAUGAG1499 CUCUCAUUU 2200
X CGAA AAUGAGAG UAUCCCUC
3719 UGAGGGAU CUGAUGAG1500 UCUCAUUUU 2201
X CGAA AAAUGAGA AUCCCUCA
3720 GUGAGGGA CUGAUGAG1501 CUCAUUUUA 2202
X CGAA AAAAUGAG UCCCUCAC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3722 AGGUGAGG CUGAUGAG1502 CAUUUUAUC 2203
X CGAA AUAAAAUG CCUCACCU
3726 CUACAGGU CUGAUGAG1503 UUAUCCCUC 2204
X CGAA AGGGAUAA ACCUGUAG
3733 UGGCAUGC CUGAUGAG1509 UCACCUGUA 2205
X CGAA ACAGGUGA GCAUGCCA
3749 UGAAACGG CUGAUGAG1505 AUGCCAGUC 2206
X CGAA ACUGGCAU CCGUUUCA
3799 CUAAAUGA CUGAUGAG1506 AGUCCCGUU 2207
X CGAA ACGGGACU UCAUUUAG
3750 ACUAAAUG CUGAUGAG1507 GUCCCGUUU 2208
X CGAA AACGGGAC CAUUUAGU
3751 GACUAAAU CUGAUGAG1508 UCCCGUUUC 2209
X CGAA AAACGGGA AUUUAGUC
3754 CAUGACUA CUGAUGAG1509 CGUUUCAUU 2210
X CGAA AUGAAACG UAGUCAUG
3755 ACAUGACU CUGAUGAG1510 GUUUCAUUU 2211
2 O X CGAA AAUGAAAC AGUCAUGU
3756 CACAUGAC CUGAUGAG1511 UUUCAUUUA 2212
X CGAA AAAUGAAA GUCAUGUG
3759 GGUCACAU CUGAUGAG1512 CAUUUAGUC 2213
X CGAA ACUAAAUG AUGUGACC
3771 ACAAGACA CUGAUGAG1513 UGACCACUC 2214
X CGAA AGUGGUCA UGUCUUGU
3775 AAACACAA CUGAUGAG1514 CACUCUGUC 2215
X CGAA ACAGAGUG UUGUGUUU
3777 GGAAACAC CUGAUGAG1515 CUCUGUCUU 2216
X CGAA AGACAGAG GUGUUUCC
3782 GCUGUGGA CUGAUGAG1516 UCUUGUGUU 2217
X CGAA ACACAAGA UCCACAGC
3783 GGCUGUGG CUGAUGAG151? CUUGUGUUU 2218
X CGAA AACACAAG CCACAGCC
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3784 AGGCUGUG CUGAUGAG1518 UUGUGUUUC 2219
X CGAA AAACACAA CACAGCCU
3799 CUGGACUG CUGAUGAG1519 CUGCAAGUU 2220
X CGAA ACUUGCAG CAGUCCAG
3800 CCUGGACU CUGAUGAG1520 UGCAAGUUC 2221
X CGAA AACUUGCA AGUCCAGG
3804 GCAUCCUG CUGAUGAG1521 AGUUCAGUC 2222
X CGAA ACUGAACU CAGGAUGC
3819 UUAGAUGU CUGAUGAG1522 AGGAUGCUA 2223
X CGAA AGCAUCCU ACAUCUAA
3819 UAUUUUUA CUGAUGAG1523 GCUAACAUC 2224
X CGAA AUGUUAGC UAAAAAUA
3821 UCUAUUUU CUGAUGAG1524 UAACAUCUA 2225
X CGAA AGAUGUUA AAAAUAGA
3827 UUUAAGUC CUGAUGAG1525 CUAAAAAUA 2226
X CGAA AUUUUUAG GACUUAAA
3832 UGAGAUUU CUGAUGAG1526 AAUAGACUU 2227
X CGAA AGUCUAUU AAAUCUCA
3833 AUGAGAUU CUGAUGAG1527 AUAGACUUA 2228
X CGAA AAGUCUAU AAUCUCAU
3837 AGCAAUGA CUGAUGAG1528 ACUUAAAUC 2229
X CGAA AUUUAAGU UCAUUGCU
3839 UAAGCAAU CUGAUGAG1529 UUAAAUCUC 2230
X CGAA AGAUUUAA AUUGCUUA
3842 UUGURAGC CUGAUGAG1530 AAUCUCAUU 2231
X CGAA AUGAGAUU GCUUACAA
3896 AGGCUUGU CUGAUGAG1531 UCAUUGCUU 2232
X CGAA AGCAAUGA ACAAGCCU
3847 UAGGCUUG CUGAUGAG1532 CAUUGCUUA 2233
X CGAA AAGCAAUG CAAGCCUA
3855 AAGAUUCU CUGAUGAG1533 ACAAGCCUA 2234
X CGAA AGGCUUGU AGAAUCUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3861 UCUGUAAA CUGAUGAG1534 CUAAGAAUC 2235
X CGAA AUUCUUAG UUUAGAGA
3863 CUUCUCUA CUGAUGAG1535 AAGAAUCUU 2236
X CGAA AGAUUCUU UAGAGAAG
3864 ACUUCUCU CUGAUGAG1536 AGAAUCUUU 2237
X CGAA AAGAUUCU AGAGAAGU
3865 UACUUCUC CUGAUGAG1537 GAAUCUUUA 2238
X CGAA AAAGAUUC GAGAAGUA
3873 CUUAUGUA CUGAUGAG1538 AGAGAAGUA 2239
X CGAA ACUUCUCU UACAUAAG
3875 AACUUAUG CUGAUGAG1539 AGAAGUAUA 2240
X CGAA AUACUUCU CAUAAGUU
3879 CCUAAACU CUGAUGAG1540 GUAUACAUA 2241
X CGAA AUGUAUAC AGUUUAGG
3883 UUAUCCUA CUGAUGAG1591 ACAUAAGUU 2242
X CGAA ACUUAUGU UAGGAUAA
3884 UUUAUCCU CUGAUGAG1542 CAUAAGUUU 2243
2 O X CGAA AACUUAUG AGGAUAAA
3885 UUUUAUCC CUGAUGAG1543 AUAAGUUUA 2244
X CGAA AAACUUAU GGAUAAAA
3890 CAUUAUUU CUGAUGAG1544 UUUAGGAUA 2245
X CGAA AUCCUAAA AAAUAAUG
3895 AAUCCCAU CUGAUGAG1545 GAUAAAAUA 2246
X CGAA AUUUUAUC AUGGGAUU
3903 GAAAAGAA CUGAUGAG1596 AAUGGGAUU 2247
X CGAA AUCCCAUU UUCUUUUC
3904 AGAAAAGA CUGAUGAG1547 AUGGGAUUU 2298
30
X CGAA AAUCCCAU UCUUUUCU
3905 AAGAAAAG CUGAUGAG1598 UGGGAUUUU 2299
X CGAA AAAUCCCA CUUUUCUU
3906 AAAGAAAA CUGAUGAG1549 GGGAUUUUC 2250
X CGAA AAAAUCCC UUUUCUUU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3908 GAAAAGAA CUGAUGAG1550 GAUUUUCUU 2251
X CGAA AGAAAAUC UUCUUUUC
3909 AGAAAAGA CUGAUGAG1551 AUUUUCUUU 2252
X CGAA AAGAAAAU UCUUUUCU
3910 GAGAAAAG CUGAUGAG1552 UUUUCUUUU 2253
X CGAA AAAGAAAA CUUUUCUC
3911 AGAGAAAA CUGAUGAG1553 UUUCUUUUC 2254
X CGAA AAAAGAAA UUUUCUCU
3913 CCAGAGAA CUGAUGAG1554 UCUUUUCUU 2255
X CGAA AGAAAAGA UUCUCUGG
3914 ACCAGAGA CUGAUGAG1555 CUUUUCUUU 2256
X CGAA AAGAAAAG UCUCUGGU
3915 UACCAGAG CUGAUGAG1556 UUUUCUUUU 2257
X CGAA AAAGAAAA CUCUGGUA
3916 UUACCAGA CUGAUGAG1557 UUUCUUUUC 2258
X CGAA AAAAGAAA UCUGGUAA
3918 UAUUACCA CUGAUGAG1558 UCUUUUCUC 2259
2 O X CGAA AGAAAAGA UGGUAAUA
3923 GUCAAUAU CUGAUGAG1559 UCUCUGGUA 2260
X CGAA ACCAGAGA AUAUUGAC
3926 CAAGUCAA CUGAUGAG1560 CUGGUAAUA 2261
X CGAA AUUACCAG UUGACUUG
3928 UACAAGUC CUGAUGAG1561 GGUAAUAUU 2262
X CGAA AUAUUACC GACUUGUA
3933 AAAUAUAC CUGAUGAG1562 UAUUGACUU 2263
X CGAA AGUCAAUA GUAUAUUU
3936 UUAAAAUA CUGAUGAG1563 UGACUUGUA 2264
X CGAA ACAAGUCA UAUUUUAA
3938 UCUUAAAA CUGAUGAG1564 ACUUGUAUA 2265
X CGAA AUACAAGU UUUUAAGA
3940 UUUCUUAA CUGAUGAG1565 UUGUAUAUU 2266
X CGAA AUAUACAA UUAAGAAA
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3941 AUUUCUUA CUGAUGAG1566 UGUAUAUUU 2267
X CGAA AAUAUACA UAAGAAAU
3942 UAUUUCUU CUGAUGAG1567 GUAUAUUUU 2268
X CGAA AAAUAUAC AAGAAAUA
3993 UUAUUUCU CUGAUGAG1568 UAUAUUUUA 2269
X CGAA AAAAUAUA AGAAAUAA
3950 CUUUCUGU CUGAUGAG1569 UAAGAAAUA 2270
X CGAA AUUUCUUA ACAGAAAG
3971 GUCUCCCA CUGAUGAG1570 GGUGACAUU 2271
X CGAA AUGUCACC UGGGAGAC
3972 UGUCUCCC CUGAUGAG1571 GUGACAUUU 2272
X CGAA AAUGUCAC GGGAGACA
3989 AAUAUAUA CUGAUGAG1572 UGUGACAUU 2273
X CGAA AUGUCACA UAUAUAUU
3990 CAAUAUAU CUGAUGAG1573 GUGACAUUU 2274
X CGAA AAUGUCAC AUAUAUUG
3991 UCAAUAUA CUGAUGAG1574 UGACAUUUA 2275
X CGAA AAAUGUCA UAUAUUGA
3993 AUUCAAUA CUGAUGAG1575 ACAUUUAUA 2276
X CGAA AUAAAUGU UAUUGAAU
3995 UAAUUCAA CUGAUGAG1576 AUUUAUAUA 2277
X CGAA AUAUAAAU UUGAAUUA
2 5
3997 AUUAAUUC CUGAUGAG1577 UUAUAUAUU 2278
X CGAA AUAUAUAA GAAUUAAU
4002 GGGAUAUU CUGAUGAG1578 UAUUGAAUU 2279
X CGAA AUUCAAUA AAUAUCCC
9003 AGGGAUAU CUGAUGAG1579 AUUGAAUUA 2280
X CGAA AAUUCAAU AUAUCCCU
9006 UGUAGGGA CUGAUGAG1580 GAAUUAAUA 2281
X CGAA AUUAAUUC UCCCUACA
4008 CAUGUAGG CUGAUGAG1581 AUUAAUAUC 2282
X CGAA AUAUUAAU CCUACAUG
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
9012 AAUACAUG CUGAUGAG1582 AUAUCCCUA 2283
X CGAA AGGGAUAU CAUGUAUU
4018 AUGUGCAA CUGAUGAG1583 CUACAUGUA 2284
X CGAA ACAUGUAG UUGCACAU
4020 CAAUGUGC CUGAUGAG1584 ACAUGUAUU 2285
X CGAA AUACAUGU GCACAUUG
4027 CUUUUUAC CUGAUGAG1585 UUGCACAUU 2286
X CGAA AUGUGCAA GUAAAAAG
4030 AAACUUUU CUGAUGAG1586 CACAUUGUA 2287
X CGAA ACAAUGUG AAAAGUUU
4037 AAAACUAA CUGAUGAG1587 UAAAAAGUU 2288
X CGAA ACUUUUUA UUAGUUUp
9038 CAAAACUA CUGAUGAG1588 AAAAAGUUU 2289
X CGAA AACUUUUU UAGUUUUG
4039 UCAAAACU CUGAUGAG1589 AAAAGUUUU 2290
X CGAA AAACUUUU AGUUUUGA
4040 AUCAAAAC CUGAUGAG1590 AAAGUUUUA 2291
X CGAA AAAACUUU GUUUUGAU
9043 CUCAUCAA CUGAUGAG1591 GUUUUAGUU 2292
X CGAA ACUAAAAC UUGAUGAG
4044 ACUCAUCA CUGAUGAG1592 UUUUAGUUU 2293
X CGAA AACUAAAA UGAUGAGU
4045 AACUCAUC CUGAUGAG1593 UUUAGUUUU 2294
X CGAA AAACUAAA GAUGAGUU
4053 AAACUCAC CUGAUGAG1594 UGAUGAGUU 2295
X CGAA ACUCAUCA GUGAGUUU
4060 ACAAGGUA CUGAUGAG1595 UUGUGAGUU 2296
X CGAA ACUCACAA UACCUUGU
4061 UACAAGGU CUGAUGAG1596 UGUGAGUUU 2297
X CGAA AACUCACA ACCUUGUA
9062 AUACAAGG CUGAUGAG1597 GUGAGUUUA 2298
X CGAA AAACUCAC CCUUGUAU
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Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
4066 CAGUAUAC CUGAUGAG1598 GUUUACCUU 2299
X CGAA AGGUAAAC GUAUACUG
4069 CUACAGUA CUGAUGAG1599 UACCUUGUA 2300
X CGAA ACAAGGUA UACUGUAG
9071 GCCUACAG CUGAUGAG1600 CCUUGUAUA 2301
X CGAA AUACAAGG CUGUAGGC
4076 AGUGUGCC CUGAUGAG1601 UAUACUGUA 2302
X CGAA ACAGUAUA GGCACACU
4085 UCAGUGCA CUGAUGAG1602 GGCACACUU 2303
X CGAA AGUGUGCC UGCACUGA
4086 AUCAGUGC CUGAUGAG1603 GCACACUUU 2304
X CGAA AAGUGUGC GCACUGAU
9095 UCAUGAUA CUGAUGAG1604 GCACUGAUA 2305
X CGAA AUCAGUGC UAUCAUGA
4097 ACUCAUGA CUGAUGAG1605 ACUGAUAUA 2306
X CGAA AUAUCAGU UCAUGAGU
9099 UCACUCAU CUGAUGAG1606 UGAUAUAUC 2307
2 O X CGAA AUAUAUCA AUGAGUGA
4110 AAGACAUU CUGAUGAG1607 GAGUGAAUA 2308
X CGAA AUUCACUC AAUGUCUU
4116 GUAGGCAA CUGAUGAG1608 AUAAAUGUC 2309
X CGAA ACAUUUAU UUGCCUAC
4118 GAGUAGGC CUGAUGAG1609 AAAUGUCUU 2310
X CGAA AGACAUUU GCCUACUC
4123 UUUUUGAG CUGAUGAG1610 UCUUGCCUA 2311
X CGAA AGGCAAGA CUCAAAAA
9126 UUUUUUUU CUGAUGAG1611 UGCCUACUC 2312
3 O
X CGAA AGUAGGCA AAAAAAAA
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TABLE VI: HAIRPIN RIZOZYMES AND TRARGET SITES FOR TIE-2
Seq. Seq. I.D.
PositionRZ I.D. SubstrateNo.
No.
AGAAGG AGAA GCAC ACCAGAGAAACA2313 GUGCU 2381
GUU
X GUACAUUACCUGGUA CCUUCU
5 76 AAACCC AGAR GUUU ACCAGAGAAACA2319 AAACC 2382
GCU
X GUACAUUACCUGGUA GGGUUU
164 GAACUA AGAA GGCU ACCAGAGAAACA2315 AGCCA 2383
GCU
X GUACAUUACCUGGUA UAGUUC
185 GGAGCA AGAA GACU ACCAGAGAAACA2316 AGUCA 2384
GCU
10 X GUACAUUACCUGGUA UGCUCC
256 UUCAGC AGAR GAUA ACCAGAGAAACA2317 UAUCU 2385
GAU
X GUACAUUACCUGGUA GCUGAA
360 ACUUCC AGAA GAUC ACCAGAGAAACA2318 GAUCC 2386
GCU
X GUACAUUACCUGGUA GGAAGU
681 GCAUGA AGAR GGUG ACCAGAGAAACA2319 CACCU 2387
GCC
X GUACAUUACCUGGUA UCAUGC
693 UCCUGG AGAA GAGC ACCAGAGAAACA2320 GCUCA 2388
GCC
X GUACAUUACCUGGUA CCAGGA
751 GGUGAA AGAR GAGG ACCAGAGAAACA2321 CCUCG 2389
GCC
X GUACAUUACCUGGUA UUCACC
818 AAGCAG AGAR GAGA ACCAGAGAAACA2322 UCUCU 2390
GUA
X GUACAUUACCUGGUA CUGCUU
823 CAUACA AGAA GUAC ACCAGAGAAACA2323 GUACU 2391
GCU
X GUACAUUACCUGGUA UGUAUG
986 CAGGGA AGAA GAAC ACCAGAGAAACA2324 GUUCU 2392
GUC
X GUACAUUACCUGGUA UCCCUG
994 AUAGGG AGAA GGGA ACCAGAGAAACA2325 UCCCU 2393
GAC
X GUACAUUACCUGGUA CCCUAU
1075 CUUACA AGAA GGCC ACCAGAGAAACA2326 GGCCA 2394
GAU
X GUACAUUACCUGGUA UGUAAG
1094 UGUUGC AGAA GCAC ACCAGAGAAACA232? GUGCA 2395
GCU
X GUACAUUACCUGGUA GCAACA
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Seq. Seq. I.D.
PositionRZ I.D. SubstrateNo.
No.
1139 CUGGAG AGAA GAGA ACCAGAGAAACA2328 UCUCU 2396
GCU
X GUACAUUACCUGGUA CUCCAG
1216 UAUAUG AGAR GGCA ACCAGAGAAACA2329 UGCCA 2397
GAU
X GUACAUUACCUGGUA CAUAUA
1312 UGUCCC AGAA GGCU ACCAGAGAAACA2330 AGCCG 2398
GAU
X GUACAUUACCUGGUA GGGACA
1351 GAAAUG AGAR GURU ACCAGAGAAACA2331 AUACG 2399
GAU
X GUACAUUACCUGGUA CAUUUC
1363 UAUGGC AGAA GAGA ACCAGAGAAACA2332 UCUCA 2400
GUA
X GUACAUUACCUGGUA GCCAUA
1386 GGGAGG AGAA GGUG ACCAGAGAAACA2333 CACCG 2401
GAU
X GUACAUUACCUGGUA CCUCCC
1399 UCCUGA AGAA GGGG ACCAGAGAAACA2334 CCCCU 2402
GAC
X GUACAUUACCUGGUA UCAGGA
1594 GCUCAG AGAR GAUG ACCAGAGAAACA2335 CAUCA 2903
GCU
X GUACAUUACCUGGUA CUGAGC
1709 CUCCAC AGAA GACC ACCAGAGAAACA2336 GGUCC 2404
GUC
X GUACAUUACCUGGUA ' GUGGAG
1762 GAUAGA AGAA GUUG ACCAGAGAAACA2337 CAACA 2405
GCU
X GUACAUUACCUGGUA UCUAUC
1772 GAGGGA AGAA GAUA ACCAGAGAAACA2338 UAUCG 2406
GAC
X GUACAUUACCUGGUA UCCCUC
1803 CUUUUA AGAA GGAG ACCAGAGAAACA2339 CUCCU 2407
GCC
X GUACAUUACCUGGUA UAAAAG
1815 AGAGUG AGAA GACU ACCAGAGAAACA2340 AGUCA 2408
GAC
X GUACAUUACCUGGUA CACUCU
1977 ACCACG AGAR GCUC ACCAGAGAAACA2341 GAGCA 2909
GUA
X GUACAUUACCUGGUA CGUGGU
2038 GGUCCA AGAA GUGA ACCAGAGAAACA2342 UCACU 2410
GCU
X GUACAUUACCUGGUA UGGACC
2110 AAUCAC AGAR GAGG ACCAGAGAAACA2343 CCUCG 2411
GCU
X GUACAUUACCUGGUA GUGAUU
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Seq. Seq. I.D.
PositionRZ I.D. SubstrateNo.
No.
2235 AGCUGA AGAR GAAU ACCAGAGAAACA2344 AUUCA 2412
GUA
X GUACAUUACCUGGUA UCAGCU
2241 CCCUUG AGAR GAUA ACCAGAGAAACA2395 UAUCA 2413
GCU
X GUACAUUACCUGGUA CAAGGG
2317 AGAAAA AGAA GGGU ACCAGAGAAACA2346 ACCCA 2414
GCC
X GUACAUUACCUGGUA UUUUCU
2365 UCCGAG AGAR GCUG ACCAGAGAAACA2347 CAGCG 2415
GAC
X GUACAUUACCUGGUA CUCGGA
2388 GCUAUA AGAA GCAU ACCAGAGAAACA2348 AUGCU 2416
GCU
X GUACAUUACCUGGUA UAUAGC
2410 CAUUCC AGAA GAGC ACCAGAGAAACA2349 GCUCU 2417
GCU
X GUACAUUACCUGGUA GGAAUG
2423 CAGUCA AGAA GGUC ACCAGAGAAACA2350 GACCU 2418
GCC
X GUACAUUACCUGGUA UGACUG
2427 AGCACA AGAA GGCA ACCAGAGAAACA2351 UGCCU 2419
GAC
X GUACAUUACCUGGUA UGUGCU
2436 AAGGCC AGAA GCAC ACCAGAGAAACA2352 GUGCU 2420
GUU
X GUACAUUACCUGGUA GGCCUU
2948 AAUAUG AGAR GAAA ACCAGAGAAACA2353 UUUCU 2421
GAU
X GUACAUUACCUGGUA CAUAUU
2524 CUGCAC AGAR GGUU ACCAGAGAAACA2354 AACCA 2422
GCU
X GUACAUUACCUGGUA GUGCAG
2 5
2532 GAGUUG AGAA GCAC ACCAGAGAAACA2355 GUGCA 2423
GUU
X GUACAUUACCUGGUA CAACUC
2581 UGUAGG AGAR GGGU ACCAGAGAAACA2356 ACCCA 2924
GAU
X GUACAUUACCUGGUA CCUACA
2694 GCAUCC AGAR GUAA ACCAGAGAAACA2357 UUACG 2425
GAU
3a
X GUACAUUACCUGGUA GGAUGC
2914 UGCUGG AGAA GUCU ACCAGAGAAACA2358 AGACG 2926
GAC
X GUACAUUACCUGGUA CCAGCA
2955 UGGGAG AGAA GUGU ACCAGAGAAACA2359 ACACU 2927
GUC
X GUACAUUACCUGGUA CUCCCA
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Seq. Seq. I.D.
PositionRZ I.D. SubstrateNo.
No.
2967 UGAAGG AGAR GCUG ACCAGAGAAACA2360 CAGCA 2428
GCU
X GUACAUUACCUGGUA CCUUCA
2983 CACGUC AGAA GCGA ACCAGAGAAACA2361 UCGCU 2429
GCC
X GUACAUUACCUGGUA GACGUG
2986 GGCCAC AGAA GCAG ACCAGAGAAACA2362 CUGCC 2430
GAC
X GUACAUUACCUGGUA GUGGCC
3024 UGGAUA AGAA GUUU ACCAGAGAAACA2363 AAACA 2431
GUU
X GUACAUUACCUGGUA UAUCCA
3091 UCCAAA AGAR GCUA ACCAGAGAAACA2369 UAGCA 2932
GAU
X GUACAUUACCUGGUA UUUGGA
3300 CCCUGG AGAA GCUU ACCAGAGAAACA2365 AAGCU 2433
GCC
X GUACAUUACCUGGUA CCAGGG
3319 UCUCCA AGAR GUAG ACCAGAGAAACA2366 CUACA 2434
GAC
X GUACAUUACCUGGUA UGGAGA
3500 CAGCAG AGAR GUCA ACCAGAGAAACA2367 UGACU 2435
GUU
X GUACAUUACCUGGUA CUGCUG
3505 UUCUUC AGAR GAAC ACCAGAGAAACA2368 GUUCU 2936
GCU
X GUACAUUACCUGGUA GAAGAA
3517 GUCCUA AGAA GCUU ACCAGAGAAACA2369 AAGCG 2437
GCC
X GUACAUUACCUGGUA UAGGAC
3535 AGGGUA AGAA GAUG ACCAGAGAAACA2370 CAUCU 2438
GUA
X GUACAUUACCUGGUA UACCCU
3546 AAGGGA AGAA GAGG ACCAGAGAAACA2371 CCUCU 2439
GUU
X GUACAUUACCUGGUA UCCCUU
3583 UUUCUC AGAA GUUG ACCAGAGAAACA2372 CAACU 2440
GCU
X GUACAUUACCUGGUA GAGAAA
3700 AGAAGA AGAA GAUU ACCAGAGAAACA2373 AAUCA 2441
GAU
X GUACAUUACCUGGUA UCUUCU
3730 GCAUGC AGAA GGUG ACCAGAGAAACA2374 CACCU 2442
GUA
X GUACAUUACCUGGUA GCAUGC
3741 AAACGG AGAR GGCA ACCAGAGAAACA2375 UGCCA 2443
GUC
X GUACAUUACCUGGUA CCGUUU
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Seq. Seq. I.D.
PositionRZ I.D. SubstrateNo.
No.
3796 AAAUGA AGAA GGAC ACCAGAGAAACA2376 GUCCC 2494
GUU
X GUACAUUACCUGGUA UCAUUU
3772 ACACAA AGAR GAGU ACCAGAGAAACA2377 ACUCU 2495
GUC
X GUACAUUACCUGGUA UUGUGU
3788 CUUGCA AGAA GUGG ACCAGAGAAACA2378 CCACA 2446
GCC
X GUACAUUACCUGGUA UGCAAG
3801 AUCCUG AGAR GAAC ACCAGAGAAACA2379 GUUCA 2447
GUC
X GUACAUUACCUGGUA CAGGAU
4073 UGUGCC AGAA GURU ACCAGAGAAACA2380 AUACU 2998
GUA
X GUACAUUACCUGGUA GGCACA
20
30
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TABLE VI I: HAMMERHEAD RIBOZYME AND TARGET SITE SEQUENCES FOR INTEGRIN
ALPHA 6 SUBUNIT
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
11 ACCCCCGG CUGAUGAG 2449 GCGACCGUC 3588
X
CGAA ACGGUCGC CCGGGGGU
63 GCUGCUGC CUGAUGAG 2450 GGUGCGGUA 3589
X
CGAA ACCGCAGC GCAGCAGC
82 CUGGGUCC CUGAUGAG 2451 GGCAGCCUC 3590
X
CGAA AGGCUGCC GGACCCAG
119 GGAGCGGG CUGAUGAG 2452 CUGCAGGUC 3591
X
CGAA ACCUGCAG CCCGCUCC
126 GGGGAGGG CUGAUGAG 2453 UCCCCGCUC 3592
X
CGAA AGCGGGGA CCCUCCCC
131 CGCACGGG CUGAUGAG 2454 GCUCCCCUC 3593
X
CGAA AGGGGAGC CCCGUGCG
141 CAUGGGCG CUGAUGAG 2455 CCGUGCGUC 3599
X
CGAA ACGCACGG CGCCCAUG
172 GGUAGAGC CUGAUGAG 2456 GCUGUGCUU 3595
X
CGAA AGCACAGC GCUCUACC
176 GACAGGUA CUGAUGAG 2457 UGCUUGCUC 3596
X
CGAA AGCAAGCA UACCUGUC
178. CCGACAGG CUGAUGAG 2458 CUUGCUCUA 3597
X
CGAA AGAGCAAG CCUGUCGG
184 GCCCCGCC CUGAUGAG 2459 CUACCUGUC 3598
X
CGAA ACAGGUAG GGCGGGGC
194 CGGGACAG CUGAUGAG 2960 GCGGGGCUC 3599
X
CGAA AGCCCCGC CUGUCCCG
199 CGAGCCGG CUGAUGAG 2961 GCUCCUGUC 3600
X
CGAA ACAGGAGC CCGGCUCG
206 GCUGCGCC CUGAUGAG 2962 UCCCGGCUC 3601
X
CGAA AGCCGGGA GGCGCAGC
217 CCAAGUUG CUGAUGAG 2463 CGCAGCCUU 3602
X
CGAA AGGCUGCG CAACUUGG
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Seq. Seq. I.D.
T.D.
Position RZ No. Substrate No.
218 UCCAAGUU CUGAUGAG 2964 GCAGCCUUC 3603
X
CGAA AAGGCUGC AACUUGGA
223 GAGUGUCC CUGAUGAG 2465 CUUCAACUU 3609
X
CGAA AGUUGAAG GGACACUC
231 GUCCUCCC CUGAUGAG 2466 UGGACACUC 3605
X
CGAA AGUGUCCA GGGAGGAC
248 UAUUUCCG CUGAUGAG 2467 AACGUGAUC 3606
X
CGAA AUCACGUU CGGAAAUA
256 GGUCUCCA CUGAUGAG 2968 CCGGAAAUA 3607
X
CGAA AUUUCCGG UGGAGACC
275 AAGCCGAA CUGAUGAG 2469 GGGAGCCUC 3608
X
CGAA AGGCUCCC UUCGGCUU
277 AGAAGCCG CUGAUGAG 2470 GAGCCUCUU 3609
X
CGAA AGAGGCUC CGGCUUCU
278 GAGAAGCC CUGAUGAG 2471 AGCCUCUUC 3610
X
CGAA AAGAGGCU GGCUUCUC
283 CCAGCGAG CUGAUGAG 2972 CUUCGGCUU 3611
X
CGAA AGCCGAAG CUCGCUGG
284 GCCAGCGA CUGAUGAG 2473 UUCGGCUUC 3612
X
CGAA AAGCCGAA UCGCUGGC
286 UGGCCAGC CUGAUGAG 2474 CGGCUUCUC 3613
X
CGAA AGAAGCCG GCUGGCCA
331 CCACGAGC CUGAUGAG 2475 GCGGCUGUU 3614
X
CGAA ACAGCCGC GCUCGUGG
335 GCCCCCAC CUGAUGAG 2476 CUGUUGCUC 3615
X
CGAA AGCAACAG GUGGGGGC
362 UGCAGUGG CUGAUGAG 2477 GAAGCGCUU 3616
X
CGAA AGCGCUUC CCACUGCA
363 CUGCAGUG CUGAUGAG 2478 AAGCGCUUC 3617
X
CGAA AAGCGCUU CACUGCAG
397 CGCAGCUG CUGAUGAG 2479 AGGGCUGUA 3618
X
CGAA ACAGCCCU CAGCUGCG
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Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
410 CGGGCGGU CUGAUGAG 2480 UGCGACAUC 3619
X
CGAA AUGUCGCA ACCGCCCG
437 UCAAACUC CUGAUGAG 2481 ACGCGGAUC 3620
X
CGAA AUCCGCGU GAGUUUGA
442 CGUUAUCA CUGAUGAG 2482 GAUCGAGUU 3621
X
CGAA ACUCGAUC UGAUAACG
443 UCGUUAUC CUGAUGAG 2483 AUCGAGUUU 3622
X
CGAA AACUCGAU GAUAACGA
497 AGCAUCGU CUGAUGAG 2984 AGUUUGAUA 3623
X
CGAA AUCAAACU ACGAUGCU
466 UGCUUUCU CUGAUGAG 2985 CCCCACGUC 3624
X
CGAA ACGUGGGG AGAAAGCA
483 CAUCCACU CUGAUGAG 2986 AGGAAGAUC 3625
X
CGAA AUCUUCCU AGUGGAUG
497 UGGACGGU CUGAUGAG 2987 AUGGGGGUC 3626
X
CGAA ACCCCCAU ACCGUCCA
503 UGGCUCUG CUGAUGAG 2488 GUCACCGUC 3627
X
2 O CGAA ACGGUGAC CAGAGCCA
516 GCCCCCUG CUGAUGAG 2489 GCCAAGGUC 3628
X
CGAA ACCUUGGC CAGGGGGC
530 CAUGUCAC CUGAUGAG 2990 GGCAAGGUC 3629
X
CGAA ACCUUGCC GUGACAUG
2 5 593 AUAUCGGU CUGAUGAG 2491 CAUGUGCUC 3630
X
CGAA AGCACAUG ACCGAUAU
550 UUUUUUCA CUGAUGAG 2492 UCACCGAUA 3631
X
CGAA AUCGGUGA UGAAAAAA
569 UUCGUAUU CUGAUGAG 2993 CAGCAUGUU 3632
X
30
CGAA ACAUGCUG AAUACGAA
570 CUUCGUAU CUGAUGAG 2999 AGCAUGUUA 3633
X
CGAA AACAUGCU AUACGAAG
573 CUGCUUCG CUGAUGAG 2495 AUGUUAAUA 3634
X
CGAA AUUAACAU CGAAGCAG
CA 02324421 2000-09-26
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144
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
586 UGUCUCGG CUGAUGAG 2496 GCAGGAAUC 3635
X
CGAA AUUCCUGC CCGAGACA
596 CGCCCAAA CUGAUGAG 2497 CGAGACAUC 3636
X
CGAA AUGUCUCG UUUGGGCG
598 ACCGCCCA CUGAUGAG 2498 AGACAUCUU 3637
X
CGAA AGAUGUCU UGGGCGGU
599 CACCGCCC CUGAUGAG 2499 GACAUCUUU 3638
X
CGAA AAGAUGUC GGGCGGUG
609 CAGGACAU CUGAUGAG 2500 GGCGGUGUU 3639
X
CGAA ACACCGCG AUGUCCUG
610 UCAGGACA CUGAUGAG 2501 GCGGUGUUA 3640
X
CGAA AACACCGC UGUCCUGA
614 UGACUCAG CUGAUGAG 2502 UGUUAUGUC 3641
X
CGAA ACAUAACA CUGAGUCA
621 GAGAUUCU CUGAUGAG 2503 UCCUGAGUC 3642
X
CGAA ACUCAGGA AGAAUCUC
627 AAUCCUGA CUGAUGAG 2504 GUCAGAAUC 3643
X
CGAA AUUCUGAC UCAGGAUU
629 UCAAUCCU CUGAUGAG 2505 CAGAAUCUC 3644
X
CGAA AGAUUCUG AGGAUUGA
635 UCGUCUUC CUGAUGAG 2506 CUCAGGAUU 3695
X
CGAA AUCCUGAG GAAGACGA
695 CCCAUCCA CUGAUGAG 2507 AAGACGAUA 3646
X
CGAA AUCGUCUU UGGAUGGG
660 AAAGCUCC CUGAUGAG 2508 GGGGAGAUU 3647
X
CGAA AUCUCCCC GGAGCUUU
667 CAUCACAA CUGAUGAG 2509 UUGGAGCUU 3648
X
CGAA AGCUCCAA UUGUGAUG
668 CCAUCACA CUGAUGAG 2510 UGGAGCUUU 3649
X
CGAA AAGCUCCA UGUGAUGG
669 CCCAUCAC CUGAUGAG 2511 GGAGCUUUU 3650
X
CGAA AAAGCUCC GUGAUGGG
CA 02324421 2000-09-26
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145
Seq. Seq. I.D.
I.D.
Position R2 No. Substrate No.
682 GGCCUCUC CUGAUGAG 2512 UGGGCGAUU 3651
X
CGAA AUCGCCCA GAGAGGCC
700 AAGAGCCA CUGAUGAG 2513 UGAGAAAUU 3652
X
CGAA AUUUCUCA UGGCUCUU
701 CAAGAGCC CUGAUGAG 2514 GAGAAAUUU 3653
X
CGAA AAUUUCUC GGCUCUUG
706 GCUGGCAA CUGAUGAG 2515 AUUUGGCUC 3654
X
CGAA AGCCAAAU UUGCCAGC
708 UUGCUGGC CUGAUGAG 2516 UUGGCUCUU 3655
X
CGAA AGAGCCAA GCCAGCAA
722 GUAGCUGC CUGAUGAG 2517 CAAGGUGUA 3656
X
CGAA ACACCUUG GCAGCUAC
729 AGUAAAAG CUGAUGAG 2518 UAGCAGCUA 3657
X
CGAA AGCUGCUA CUUUUACU
732 UUUAGUAA CUGAUGAG 2519 CAGCUACUU 3658
X
CGAA AGUAGCUG UUACUAAA
733 CUUUAGUA CUGAUGAG 2520 AGCUACUUU 3659
X
2 O CGAA AAGUAGCU UACUAAAG
739 UCUUUAGU CUGAUGAG 2521 GCUACUUUU 3660
X
CGAA AAAGUAGC ACUAAAGA
735 GUCUUUAG CUGAUGAG 2522 CUACUUUUA 3661
X
CGAA AAAAGUAG CUAAAGAC
738 AAAGUCUU CUGAUGAG 2523 CUUUUACUA 3662
X
CGAA AGUAAAAG AAGACUUU
745 UGUAAUGA CUGAUGAG 2524 UAAAGACUU 3663
X
CGAA AGUCUUUA UCAUUACA
746 AUGUAAUG CUGAUGAG 2525 AAAGACUUU 3664
X
CGAA AAGUCUUU CAUUACAU
747 AAUGUAAU CUGAUGAG 2526 AAGACUUUC 3665
X
CGAA AAAGUCUU AUUACAUU
750 UACAAUGU CUGAUGAG 2527 ACUUUCAUU 3666
X
CGAA AUGAAAGU ACAUUGUA
CA 02324421 2000-09-26
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146
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
751 AUACAAUG CUGAUGAG 2528 CUUUCAUUA 3667
X
CGAA AAUGAAAG CAUUGUAU
755 CCAAAUAC CUGAUGAG 2529 CAUUACAUU 3668
X
CGAA AUGUAAUG GUAUUUGG
758 GCUCCAAA CUGAUGAG 2530 UACAUUGUA 3669
X
CGAA ACAAUGUA UUUGGAGC
760 GGGCUCCA CUGAUGAG 2531 CAUUGUAUU 3670
X
CGAA AUACAAUG UGGAGCCC
761 GGGGCUCC CUGAUGAG 2532 AUUGUAUUU 3671
X
CGAA AAUACAAU GGAGCCCC
779 GUUAUAAG CUGAUGAG 2533 CCCCGGGUA 3672
X
CGAA ACCCGGGG CUUAUAAC
777 CCAGUUAU CUGAUGAG 2534 CGGGUACUU 3673
X
CGAA AGUACCCG AUAACUGG
778 UCCAGUUA CUGAUGAG 2,535 GGGUACUUA 3674
X
CGAA AAGUACCC UAACUGGA
780 UUUCCAGU CUGAUGAG 2536 GUACUUAUA 3675
X
2 O CGAA AUAAGUAC ACUGGAAA
799 ACACGAAC CUGAUGAG 2537 AAAGGGAUU 3676
X
CGAA AUCCCUUU GUUCGUGU
797 UCUACACG CUGAUGAG 2538 GGGAUUGUU 3677
X
CGAA ACAAUCCC CGUGUAGA
79g CUCUACAC CUGAUGAG 2539 GGAUUGUUC 3678
X
CGAA AACAAUCC GUGUAGAG
803 UUUUGCUC CUGAUGAG 2590 GUUCGUGUA 3679
X
CGAA ACACGAAC GAGCAAAA
816 AAAAGUGU CUGAUGAG 2541 AAAAGAAUA 3680
X
CGAA AUUCUUUU ACACUUUU
822 GUCAAAAA CUGAUGAG 2542 AUAACACUU 3681
X
CGAA AGUGUUAU UUUUUGAC
823 UGUCAAAA CUGAUGAG 2593 UAACACUUU 3682
X
CGAA AAGUGUUA UUUUGACA ~
I
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
147
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
829 AUGUCAAA CUGAUGAG 2549 AACACUUUU 3683
X
CGAA AAAGUGUU UUUGACAU
825 CAUGUCAA CUGAUGAG 2545 ACACUUUUU 3689
X
CGAA AAAAGUGU UUGACAUG
826 UCAUGUCA CUGAUGAG 2596 CACUUUUUU 3685
X
CGAA AAAAAGUG UGACAUGA
827 UUCAUGUC CUGAUGAG 2547 ACUUUUUUU 3686
X
CGAA AAAAAAGU GACAUGAA
839 UCUUCAAA CUGAUGAG 2548 AUGAACAUC 3687
X
CGAA AUGUUCAU UUUGAAGA
891 CAUCUUCA CUGAUGAG 2549 GAACAUCUU 3688
X
CGAA AGAUGUUC UGAAGAUG
842 CCAUCUUC CUGAUGAG 2550 AACAUCUUU 3689
X
CGAA AAGAUGUU GAAGAUGG
855 AACUUCAU CUGAUGAG 2551 AUGGGCCUU 3690
X
CGAA AGGCCCAU AUGAAGUU
856 CAACUUCA CUGAUGAG 2552 UGGGCCUUA 3691
X
CGAA AAGGCCCA UGAAGUUG
863 UCUCCACC CUGAUGAG 2553 UAUGAAGUU 3692
X
CGAA ACUUCAUA GGUGGAGA
891 AGGAACGA CUGAUGAG 2554 AUGAAAGUC 3693
X
CGAA ACUUUCAU UCGUUCCU
2 5
gg3 ACAGGAAC CUGAUGAG 2555 GAAAGUCUC 3694
X
CGAA AGACUUUC GUUCCUGU
896 GGAACAGG CUGAUGAG 2556 AGUCUCGUU 3695
X
CGAA ACGAGACU CCUGUUCC
897 AGGAACAG CUGAUGAG 2557 GUCUCGUUC 3696
X
30
CGAA AACGAGAC CUGUUCCU
902 UUAGCAGG CUGAUGAG 2558 GUUCCUGUU 3697
X
CGAA ACAGGAAC CCUGCUAA
903 GUUAGCAG CUGAUGAG 2559 UUCCUGUUC 3698
X
CGAA AACAGGAA CUGCUAAC
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
148
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
909 GUAACUGU CUGAUGAG 2560 UUCCUGCUA 3699
X
CGAA AGCAGGAA ACAGUUAC
915 ACCUAAGU CUGAUGAG 2561 CUAACAGUU 3700
X
CGAA ACUGUUAG ACUUAGGU
916 AACCUAAG CUGAUGAG 2562 UAACAGUUA 3701
X
CGAA AACUGUUA CUUAGGUU
919 AAAAACCU CUGAUGAG 2563 CAGUUACUU 3702
X
CGAA AGUAACUG AGGUUUUU
920 GAAAAACC CUGAUGAG 2564 AGUUACUUA 3703
X
CGAA AAGUAACU GGUUUUUC
929 CAAAGAAA CUGAUGAG 2565 ACUUAGGUU 3704
X
CGAA ACCUAAGU UUUCUUUG
925 CCAAAGAA CUGAUGAG 2566 CUUAGGUUU 3705
X
CGAA AACCUAAG UUCUUUGG
926 UCCAAAGA CUGAUGAG 2567 UUAGGUUUU 3706
X
CGAA AAACCUAA UCUUUGGA
927 GUCCAAAG CUGAUGAG 2568 UAGGUUUUU 3707
X
CGAA AAAACCUA CUUUGGAC
928 AGUCCAAA CUGAUGAG 2569 AGGUUUUUC 3708
X
CGAA AAAAACCU UUUGGACU
930 UGAG(JCCA CUGAUGAG2570 GUUUUUCUU 3709
X
CGAA AGAAAAAC UGGACUCA
2 5
931 CUGAGUCC CUGAUGAG 2571 UUUUUCUUU 3710
X
CGAA AAGAAAAA GGACUCAG
937 CUUUCCCU CUGAUGAG 2572 UUUGGACUC 3711
X
CGAA AGUCCAAA AGGGAAAG
998 AGAAACAA CUGAUGAG 2573 GGAAAGGUA 3712
X
CGAA ACCUUUCC UUGUUUCU
950 UUAGAAAC CUGAUGAG 2574 AAAGGUAUU 3713
X
CGAA AUACCUUU GUUUCUAA
953 UCUUUAGA CUGAUGAG 2575 GGUAUUGUU 3714
X
CGAA ACAAUACC UCUAAAGA
CA 02324421 2000-09-26
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149
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
954 AUCUUUAG CUGAUGAG 2576 GUAUUGUUU 3715
X
CGAA AACAAUAC CUAAAGAU
955 CAUCUUUA CUGAUGAG 2577 UAUUGUUUC 3716
X
CGAA AAACAAUA UAAAGAUG
957 CUCAUCUU CUGAUGAG 2578 UUGUUUCUA 3717
X
CGAA AGAAACAA AAGAUGAG
968 ACAAAAGU CUGAUGAG 2579 GAUGAGAUC 3718
X
CGAA AUCUCAUC ACUUUUGU
972 AGAUACAA CUGAUGAG 2580 AGAUCACUU 3719
X
CGAA AGUGAUCU UUGUAUCU
973 CAGAUACA CUGAUGAG 2581 GAUCACUUU 3720
X
CGAA AAGUGAUC UGUAUCUG
974 CCAGAUAC CUGAUGAG 2582 AUCACUUUU 3721
X
CGAA AAAGUGAU GUAUCUGG
977 GCACCAGA CUGAUGAG 2583 ACUUUUGUA 3722
X
CGAA ACAAAAGU UCUGGUGC
979 GAGCACCA CUGAUGAG 2584 UUUUGUAUC 3723
X
2 0 CGAA AUACAAAA UGGUGCUC
987 GGCUCUGG CUGAUGAG 2585 CUGGUGCUC 3729
X
CGAA AGCACCAG CCAGAGCC
999 UCCACUGU CUGAUGAG 2586 GAGCCAAUC 3725
X
CGAA AUUGGCUC ACAGUGGA
1016 UUCAGCAA CUGAUGAG 2587 GCCGUGGUU 3726
X
CGAA ACCACGGC UUGCUGAA
1017 CUUCAGCA CUGAUGAG 2588 CCGUGGUUU 3727
X
CGAA AACCACGG UGCUGAAG
1018 UCUUCAGC CUGAUGAG 2589 CGUGGUUUU 3728
X
CGAA AAACCACG GCUGAAGA
1039 GAUGUGCA CUGAUGAG 2590 CAUGAAGUC 3729
X
CGAA ACUUCAUG UGCACAUC
1047 AGGGAGGA CUGAUGAG 2591 CUGCACAUC 3730
X
CGAA AUGUGCAG UCCUCCCU
CA 02324421 2000-09-26
WO 99/50403 PCTNS99106507
150
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1099 UCAGGGAG CUGAUGAG 2592 GCACAUCUC 3731
X
CGAA AGAUGUGC CUCCCUGA
1052 UGCUCAGG CUGAUGAG 2593 CAUCUCCUC 3732
X
CGAA AGGAGAUG CCUGAGCA
1069 CCAUCGAA CUGAUGAG 2594 GAGCACAUA 3733
X
CGAA AUGUGCUC UUCGAUGG
1066 CUCCAUCG CUGAUGAG 2595 GCACAUAUU 3734
X
CGAA AUAUGUGC CGAUGGAG
1067 UCUCCAUC CUGAUGAG 2596 CACAUAUUC 3735
X
CGAA AAUAUGUG GAUGGAGA
1080 AGAGGCCA CUGAUGAG 2597 GAGAAGGUC 3736
X
CGAA ACCUUCUC UGGCCUCU
1087 CAAAUGAA CUGAUGAG 2598 UCUGGCCUC 3737
X
CGAA AGGCCAGA UUCAUUUG
1089 GCCAAAUG CUGAUGAG 2599 UGGCCUCUU 3738
X
CGAA AGAGGCCA CAUUUGGC
1090 AGCCAAAU CUGAUGAG 2600 GGCCUCUUC 3739
X
CGAA AAGAGGCC AUUUGGCU
1093 CAUAGCCA CUGAUGAG 2601 CUCUUCAUU 3740
X
CGAA AUGAAGAG UGGCUAUG
1094 UCAUAGCC CUGAUGAG 2602 UCUUCAUUU 3791
X
CGAA AAUGAAGA GGCUAUGA
2 5
1099 CCACAUCA CUGAUGAG 2603 AUUUGGCUA 3742
X
CGAA AGCCAAAU UGAUGUGG
1121 UCCUUGUU CUGAUGAG 2604 GUGGACCUC 3743
X
CGAA AGGUCCAC AACAAGGA
1193 AAUAACUA CUGAUGAG 2605 GGCAAGAUA 3744
X
CGAA AUCUUGCC UAGUUAUU
1195 CCAAUAAC CUGAUGAG 2606 CAAGAUAUA 3745
X
CGAA AUAUCUUG GUUAUUGG
1148 GCUCCAAU CUGAUGAG 2607 GAUAUAGUU 3746
X
CGAA ACUAUAUC AUUGGAGC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
151
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1149 GGCUCCAA CUGAUGAG 2608 AUAUAGUUA 3747
X
CGAA AACUAUAU UUGGAGCC
1151 GGGGCUCC CUGAUGAG 2609 AUAGUUAUU 3748
X
CGAA AUAACUAU GGAGCCCC
1165 UAUCAAAA CUGAUGAG 2610 CCCACAGUA 3749
X
CGAA ACUGUGGG UUUUGAUA
1167 UCUAUCAA CUGAUGAG 2611 CACAGUAUU 3750
X
CGAA AUACUGUG UUGAUAGA
1168 CUCUAUCA CUGAUGAG 2612 ACAGUAUUU 3751
X
CGAA AAUACUGU UGAUAGAG
1169 UCUCUAUC CUGAUGAG 2613 CAGUAUUUU 3752
X
CGAA AAAUACUG GAUAGAGA
1173 UCCAUCUC CUGAUGAG 2614 AUUUUGAUA 3753
X
CGAA AUCAAAAU GAGAUGGA
1187 GCACCUCC CUGAUGAG 2615 GGAGAAGUU 3754
X
CGAA ACUUCUCC GGAGGUGC
1201 UGUAGACA CUGAUGAG 2616 UGCAGUGUA 3755
X
2 O CGAA ACACUGCA UGUCUACA
1205 UUCAUGUA CUGAUGAG 2617 GUGUAUGUC 3756
X
CGAA ACAUACAC UACAUGAA
1207 GGUUCAUG CUGAUGAG 2618 GUAUGUCUA 3757
X
CGAA AGACAUAC CAUGAACC
2 5
1233 CUUCACAU CUGAUGAG 2619 GAUGGAAUA 3758
X
CGAA AUUCCAUC AUGUGAAG
1247 UUAAGACG CUGAUGAG 2620 AAGCCAAUU 3759
X
CGAA AUUGGCUU CGUCUUAA
1248 AUUAAGAC CUGAUGAG 2621 AGCCAAUUC 3760
X
30
CGAA AAUUGGCU GUCUUAAU
1251 UCCAUUAA CUGAUGAG 2622 CAAUUCGUC 3761
X
CGAA ACGAAUUG UUAAUGGA
1253 GUUCCAUU CUGAUGAG 2623 AUUCGUCUU 3762
X
CGAA AGACGAAU AAUGGAAC
CA 02324421 2000-09-26
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152
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1254 GGUUCCAU CUGAUGAG 2624 UUCGUCUUA 3763
X
CGAA AAGACGAA AUGGAACC
1269 AAACAUAG CUGAUGAG 2625 CCAAAGAUU 3764
X
CGAA AUCUUUGG CUAUGUUU
1270 CAAACAUA CUGAUGAG 2626 CAAAGAUUC 3765
X
CGAA AAUCUUUG UAUGUUUG
1272 GCCAAACA CUGAUGAG 2627 AAGAUUCUA 3766
X
CGAA AGAAUCUU UGUUUGGC
1276 CAAUGCCA CUGAUGAG 2628 UUCUAUGUU 3767
X
CGAA ACAUAGAA UGGCAUUG
1277 GCAAUGCC CUGAUGAG 2629 UCUAUGUUU 3768
X
CGAA AACAUAGA GGCAUUGC
1283 UUUACUGC CUGAUGAG 2630 UUUGGCAUU 3769
X
CGAA AUGCCAAA GCAGUAAA
1289 AUAUUUUU CUGAUGAG 2631 AUUGCAGUA 3770
X
CGAA ACUGCAAU AAAAAUAU
1296 AUCUCCAA CUGAUGAG 2632 UAAAAAi~IUA3771
X
2O CGAA AUUUUUUA UUGGAGAU
1298 AUAUCUCC CUGAUGAG 2633 AAAAAUAUU 3772
X
CGAA AUAUUUUU GGAGAUAU
1305 UUGAUUAA CUGAUGAG 2634 UUGGAGAUA 3773
X
CGAA AUCUCCAA UUAAUCAA
1307 UCUUGAUU CUGAUGAG 2635 GGAGAUAUU 3774
X
CGAA AUAUCUCC AAUCAAGA
1308 AUCUUGAU CUGAUGAG 2636 GAGAUAUUA 3775
X
CGAA AAUAUCUC AUCAAGAU
1311 GCCAUCUU CUGAUGAG 2637 AUAUUAAUC 3776
X
CGAA AUUAAUAU AAGAUGGC
1321 UAUCUGGG CUGAUGAG 2638 AGAUGGCUA 3777
X
CGAA AGCCAUCU CCCAGAUA
1329 AACUGCAA CUGAUGAG 2639 ACCCAGAUA 3778
X
CGAA AUCUGGGU UUGCAGUU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
153
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1331 CCAACUGC CUGAUGAG 2640 CCAGAUAUU 3779
X
CGAA AUAUCUGG GCAGUUGG
1337 GGAGCUCC CUGAUGAG 2641 AUUGCAGUU 3780
X
CGAA ACUGCAAU GGAGCUCC
1344 AUCAUACG CUGAUGAG 2642 UUGGAGCUC 3781
X
CGAA AGCUCCAA CGUAUGAU
1348 AGUCAUCA CUGAUGAG 2693 AGCUCCGUA 3782
X
CGAA ACGGAGCU UGAUGACU
1357 CCUUUCCC CUGAUGAG 2694 UGAUGACUU 3783
X
CGAA AGUCAUCA GGGAAAGG
1367 UAGAUAAA CUGAUGAG 2645 GGAAAGGUU 3789
X
CGAA ACCUUUCC UUUAUCUA
1368 AUAGAUAA CUGAUGAG 2646 GAAAGGUUU 3785
X
CGAA AACCUUUC UUAUCUAU
1369 GAUAGAUA CUGAUGAG 2647 AAAGGUUUU 3786
X
CGAA AAACCUUU UAUCUAUC
1370 UGAUAGAU CUGAUGAG 2648 AAGGUUUUU 3787
X
2 O CGAA AAAACCUU AUCUAUCA
1371 AUGAUAGA CUGAUGAG 2649 AGGUUUUUA 3788
X
CGAA AAAAACCU UCUAUCAU
1373 CCAUGAUA CUGAUGAG 2650 GUUUUUAUC 3789
X
CGAA AUAAAAAC UAUCAUGG
1375 AUCCAUGA CUGAUGAG 2651 UUUUAUCUA 3790
X
CGAA AGAUAAAA UCAUGGAU
1377 AGAUCCAU CUGAUGAG 2652 UUAUCUAUC 3?91
X
CGAA AUAGAUAA AUGGAUCU
1384 CAUUUGCA CUGAUGAG 2653 UCAUGGAUC 3792
X
CGAA AUGCAUGA UGCAAAUG
1397 UUGGUAUU CUGAUGAG 2659 AAUGGAAUA 3793
X
CGAA AUUCCAUU AAUACCAA
1901 UGGUUUGG CUGAUGAG 2655 GAAUAAAUA 3794
X
CGAA AUUUAUUC CCAAACCA
CA 02324421 2000-09-26
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154
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1418 CCCUUGAG CUGAUGAG 2656 ACACAGGUU 3795
X
CGAA ACCUGUGU CUCAAGGG
1919 ACCCUUGA CUGAUGAG 2657 CACAGGUUC 3796
X
CGAA AACCUGUG UCAAGGGU
1421 . AUACCCUU CUGAUGAG 2658 CAGGUUCUC 3797
X
CGAA AGAACCUG AAGGGUAU
1428 AGGUGAUA CUGAUGAG 2659 UCAAGGGUA 3798
X
CGAA ACCCUUGA UAUCACCU
1430 UAAGGUGA CUGAUGAG 2660 AAGGGUAUA 3799
X
CGAA AUACCCUU UCACCUUA
1432 AAUAAGGU CUGAUGAG 2661 GGGUAUAUC 3800
X
CGAA AUAUACCC ACCUUAUU
1937 UCCAAAAU CUGAUGAG 2662 UAUCACCUU 3801
X
CGAA AGGUGAUA AUUUUGGA
1938 AUCCAAAA CUGAUGAG 2663 AUCACCUUA 3802
X
CGAA AAGGUGAU UUUUGGAU
1440 AUAUCCAA CUGAUGAG 2664 CACCUUAUU 3803
X
CGAA AUAAGGUG UUGGAUAU
1941 AAUAUCCA CUGAUGAG 2665 ACCUUAUUU 3804
X
CGAA AAUAAGGU UGGAUAUU
1442 GAAUAUCC CUGAUGAG 2666 CCUUAUUUU 3805
X
CGAA AAAUAAGG GGAUAUUC
2 5
1947 CAAUUGAA CUGAUGAG 266'7 UUUUGGAUA 3806
X
CGAA AUCCAAAA UUCAAUUG
1949 AGCAAUUG CUGAUGAG 2668 UUGGAUAUU 3807
X
CGAA AUAUCCAA CAAUUGCU
1450 CAGCAAUU CUGAUGAG 2669 UGGAUAUUC 3808
X
30
CGAA AAUAUCCA AAUUGCUG
1954 UUUCCAGC CUGAUGAG 2670 UAUUCAAUU 3809
X
CGAA AUUGAAUA GCUGGAAA
1472 UUUCGAUC CUGAUGAG 2671 AUGGACCUU 3810
X
CGAA AGGUCCAU GAUCGAAA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/0650?
155
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1976 GGAAUUUC CUGAUGAG 2672 ACCUUGAUC 3811
X
CGAA AUCAAGGU GAAAUUCC
1482 AGGGUAGG CUGAUGAG 2673 AUCGAAAUU 3812
X
CGAA AUUUCGAU CCUACCCU
1483 CAGGGUAG CUGAUGAG 2674 UCGAAAUUC 3813
X
CGAA AAUUUCGA CUACCCUG
1986 CAUCAGGG CUGAUGAG 2675 AAAUUCCUA 3814
X
CGAA AGGAAUUU CCCUGAUG
1496 CCAACAGC CUGAUGAG 2676 CCUGAUGUU 3815
X
CGAA ACAUCAGG GCUGUUGG
1502 AGGGAACC CUGAUGAG 2677 GUUGCUGUU 3816
X
CGAA ACAGCAAC GGUUCCCU
1506 UGAGAGGG CUGAUGAG 2678 CUGUUGGUU 3817
X
CGAA ACCAACAG CCCUCUCA
1507 CUGAGAGG CUGAUGAG 2679 UGUUGGUUC 3818
X
CGAA AACCAACA CCUCUCAG
1511 GAAUCUGA CUGAUGAG 2680 GGUUCCCUC 3819
X
2~ CGAA AGGGAACC UCAGAUUC
1513 CUGAAUCU CUGAUGAG 2681 UUCCCUCUC 3820
X
CGAA AGAGGGAA AGAUUCAG
1518 AGUUACUG CUGAUGAG 2682 UCUCAGAUU 3821
X
CGAA AUCUGAGA CAGUAAGU
1519 UAGUUACU CUGAUGAG 2683 CUCAGAUUC 3822
X
CGAA AAUCUGAG AGUAACUA
1523 AAAAUAGU CUGAUGAG 2689 GAUUCAGUA 3823
X
CGAA ACUGAAUC ACUAUUUU
1527 UCUGAAAA CUGAUGAG 2685 CAGUAACUA 3824
X
CGAA AGUUACUG UUUUCAGA
1529 GAUCUGAA CUGAUGAG 2686 GUAACUAUU 3825
X
CGAA AUAGUUAC UUCAGAUC
1530 GGAUCUGA CUGAUGAG 2687 UAACUAUUU 3826
X
CGAA AAUAGUUA UCAGAUCC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
156
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1531 GGGAUCUG CUGAUGAG 2688 AACUAUUUU 3827
X
CGAA AAAUAGUU CAGAUCCC
1532 CGGGAUCU CUGAUGAG 2689 ACUAUUUUC 3828
X
CGAA AAAAUAGU AGAUCCCG
1537 CAGGCCGG CUGAUGAG 2690 UUUCAGAUC 3829
X
CGAA AUCUGAAA CCGGCCUG
1550 UGAAUAUU CUGAUGAG 2691 CCUGUGAUU 3830
X
CGAA AUCACAGG AAUAUUCA
1551 CUGAAUAU CUGAUGAG 2692 CUGUGAUUA 3831
X
CGAA AAUCACAG AUAUUCAG
1554 UUUCUGAA CUGAUGAG 2693 UGAUUAAUA 3832
X
CGAA AUUAAUCA UUCAGAAA
1556 GUUUUCUG CUGAUGAG 2694 AUUAAUAUU 3833
X
CGAA AUAUUAAU CAGAAAAC
1557 GGUUUUCU CUGAUGAG 2695 UUAAUAUUC 3839
X
CGAA AAUAUUAA AGAAAACC
1568 GUUACUGU CUGAUGAG 2696 AAAACCAUC 3835
X
CGAA AUGGUUUU ACAGUAAC
1574 UUAGGAGU CUGAUGAG 2697 AUCACAGUA 3836
X
CGAA ACUGUGAU ACUCCUAA
1578 UCUGUUAG CUGAUGAG 2698 CAGUAACUC 3837
X
CGAA AGUUACUG CUAACAGA
1581 AAUUCUGU CUGAUGAG 2699 UAACUCCUA 3838
X
CGAA AGGAGUUA ACAGAAUU
1589 CGGAGGUC CUGAUGAG 2700 AACAGAAUU 3839
X
CGAA AUUCUGUU GACCUCCG
1595 UUCUGGCG CUGAUGAG 2701 AUUGACCUC 3840
X
CGAA AGGUCAAU CGCCAGAA
1623 UAUCCCAC CUGAUGAG 2702 GGGCGCCUA 3841
X
CGAA AGGCGCCC GUGGGAUA
1631 UGGAGGCA CUGAUGAG 2703 AGUGGGAUA 3842
X
CGAA AUCCCACU UGCCUCCA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/OG507
157
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1637 UUAACCUG CUGAUGAG 2709 AUAUGCCUC 3843
X
CGAA AGGCAUAU CAGGUUAA
1693 CAGGAUUU CUGAUGAG 2705 CUCCAGGUU 3844
X
CGAA ACCUGGAG AAAUCCUG
1644 ACAGGAUU CUGAUGAG 2706 UCCAGGUUA 3845
X
CGAA AACCUGGA AAUCCUGU
1698 CAAAACAG CUGAUGAG 2707 GGUUAAAUC 3896
X
CGAA AUUUAACC CUGUUUUG
1653 AUAUUCAA CUGAUGAG 2708 AAUCCUGUU 3847
X
CGAA ACAGGAUU UUGAAUAU
1654 UAUAUUCA CUGAUGAG 2709 AUCCUGUUU 3848
X
CGAA AACAGGAU UGAAUAUA
1655 GUAUAUUC CUGAUGAG 2710 UCCUGUUUU 3849
X
CGAA AAACAGGA GAAUAUAC
1660 UAGCAGUA CUGAUGAG 2711 UUUUGAAUA 3850
X
CGAA AUUCAAAA UACUGCUA
1662 GUUAGCAG CUGAUGAG 2712 UUGAAUAUA 3851
X
CGAA AUAUUCAA CUGCUAAC
1668 AGCGGGGU GUGAUGAG 2713 AUACUGCUA 3852
X
CGAA AGCAGUAU ACCCCGCU
1680 AGGAUUAU CUGAUGAG 2719 CCGCUGGUU 3853
X
CGAA ACCAGCGG AUAAUCCU
1681 AAGGAUUA CUGAUGAG 2715 CGCUGGUUA 3854
X
CGAA AACCAGCG UAAUCCUU
1683 UGAAGGAU CUGAUGAG 2716 CUGGUUAUA 3855
X
CGAA AUAACCAG AUCCUUCA
1686 UAUUGAAG CUGAUGAG 2717 GUUAUAAUC 3856
X
CGAA AUUAUAAC CUUCAAUA
1689 UGAUAUUG CUGAUGAG 2718 AUAAUCCUU 3857
X
CGAA AGGAUUAU CAAUAUCA
1690 UUGAUAUU CUGAUGAG 2719 UAAUCCUUC 3858
X
CGAA AAGGAUUA AAUAUCAA
CA 02324421 2000-09-26
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158
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1694 ACAAUUGA CUGAUGAG 2720 CCUUCAAUA 3859
X
CGAA AUUGAAGG UCAAUUGU
1696 CCACAAUU CUGAUGAG 2721 UUCAAUAUC 3860
X
CGAA AUAUUGAA AAUUGUGG
1700 GUGCCCAC CUGAUGAG 2722 AUAUCAAUU 3861
X
CGAA AUUGAUAU GUGGGCAC
1712 UCAGCUUC CUGAUGAG 2723 GGCACACUU 3862
X
CGAA AGUGUGCC GAAGCUGA
1738 AUAGCCCA CUGAUGAG 2729 AAGAAAAUC 3863
X
CGAA AUUUUCUU UGGGCUAU
1745 CUUGAGGA CUGAUGAG 2725 UCUGGGCUA 3864
X
CGAA AGCCCAGA UCCUCAAG
1747 CUCUUGAG CUGAUGAG 2726 UGGGCUAUC 3865
X
CGAA AUAGCCCA CUCAAGAG
1750 GAACUCUU CUGAUGAG 2727 GCUAUCCUC 3866
X
CGAA AGGAUAGC AAGAGUUC
1757 CGAAACUG CUGAUGAG 2728 UCAAGAGUU 3867
X
2 O CGAA ACUCUUGA CAGUUUCG
1758 UCGAAACU CUGAUGAG 2729 CAAGAGUUC 3868
X
CGAA AACUCUUG AGUUUCGA
1762 GGUUUCGA CUGAUGAG 2730 AGUUCAGUU 3869
X
CGAA ACUGAACU UCGAAACC
1763 UGGUUUCG CUGAUGAG 2731 GUUCAGUUU 3870
X
CGAA AACUGAAC CGAAACCA
1769 UUGGUUUC CUGAUGAG,X2732 UUCAGUUUC 3871
CGAA AAACUGAA GAAACCAA
1776 GGGCUCAG CUGAUGAG 2733 ACCAAGGUU 3872
X
CGAA ACCUUGGU CUGAGCCC
1777 UGGGCUCA CUGAUGAG 2734 CCAAGGUUC 3873
X
CGAA AACCUUGG UGAGCCCA
1789 CUUGAGUA CUGAUGAG 2735 GCCCAAAUA 3874
X
CGAA AUUUGGGC UACUCAAG
CA 02324421 2000-09-26
WO 99/50403 PC'T/US99/06507
159
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1791 UUCUUGAG CUGAUGAG 2736 CCAAAUAUA 3875
X
CGAA AUAUUUGG CUCAAGAA
1799 UAGUUCUU CUGAUGAG 2737 AAUAUACUC 3876
X
CGAA AGUAUAUU AAGAACUA
1802 UUCAGAGU CUGAUGAG 2738 CAAGAACUA 387?
X
CGAA AGUUCUUG ACUCUGAA
1806 CCUCUUCA CUGAUGAG 2739 AACUAACUC 3878
X
CGAA AGUUAGUU UGAAGAGG
1853 UUAUCCUG CUGAUGAG 2740 CUGUGGCUA 3879
X
CGAA AGCCACAG CAGGAUAA
1860 UCUGAUAU CUGAUGAG 2791 UACAGGAUA 3880
X
CGAA AUCCUGUA AUAUCAGA
1863 AUCUCUGA CUGAUGAG 2742 AGGAUAAUA 3881
X
CGAA AUUAUCCU UCAGAGAU
1865 UUAUCUCU CUGAUGAG 2743 GAUAAUAUC 3882
X
CGAA AUAUUAUC AGAGAUAA
1872 ACGCAGUU CUGAUGAG 2744 UCAGAGAUA 3883
X
2 O CGAA AUCUCUGA AACUGCGU
1881 GGGAAUGG CUGAUGAG 2795 AACUGCGUC 3884
X
CGAA ACGCAGUU CCAUUCCC
1886 GUUAUGGG CUGAUGAG 2746 CGUCCCAUU 3885
X
CGAA AUGGGACG CCCAUAAC
1887 AGUUAUGG CUGAUGAG 2797 GUCCCAUUC 3886
X
CGAA AAUGGGAC CCAUAACU
1892 GAGGCAGU CUGAUGAG 2748 AUUCCCAUA 3887
X
CGAA AUGGGAAU ACUGCCUC
1900 UCUCCACU CUGAUGAG 2749 AACUGCCUC 3888
X
CGAA AGGCAGUU AGUGGAGA
1910 GGCUCUUG CUGAUGAG 2750 GUGGAGAUC 3889
X
CGAA AUCUCCAC CAAGAGCC
1929 GCCUACGA CUGAUGAG 2751 GCCAAGCUC 3890
X
CGAA AGCUUGGC UCGUAGGC
CA 02324421 2000-09-26
WO 99/50403 ' PCT/US99/06507
160
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
1926 UCGCCUAC CUGAUGAG 2752 CAAGCUCUC 3891
X
CGAA AGAGCUUG GUAGGCGA
1929 CACUCGCC CUGAUGAG 2753 GCUCUCGUA 3892
X
CGAA ACGAGAGC GGCGAGUG
1991 UGGAAGUG CUGAUGAG 2754 GAGUGAAUU 3893
X
CGAA AUUCACUC CACUUCCA
1992 CUGGAAGU CUGAUGAG 2755 AGUGAAUUC 3894
X
CGAA AAUUCACU ACUUCCAG
1946 ACUUCUGG CUGAUGAG 2756 AAUUCACUU 3895
X
CGAA AGUGAAUU CCAGAAGU
1997 AAGUUCUG CUGAUGAG 2757 AUUCACUUC 3896
X
CGAA AAGUGAAU CAGAAGUU
1955 AUUGGAAG CUGAUGAG 2758 CCAGAAGUU 3897
X
CGAA ACUUCUGG CUUCCAAU
1956 AAUUGGAA CUGAUGAG 2759 CAGAAGUUC 3898
X
CGAA AACUUCUG UUCCAAUU
1958 AGAAUUGG CUGAUGAG 2760 GAAGUUCUU 3899
X
2 O CGAA AGAACUUC CCAAUUCU
1959 CAGAAUUG CUGAUGAG 2761 AAGUUCUUC 3900
X
CGAA AAGAACUU CAAUUCUG
1964 GAAUUCAG CUGAUGAG 2762 CUUCCAAUU 3901
X
CGAA AUUGGAAG ~ CUGAAUUC
1965 UGAAUUCA CUGAUGAG 2763 UUCCAAUUC 3902
X
CGAA AAUUGGAA UGAAUUCA
1971 UUCAUCUG CUGAUGAG 2769 UUCUGAAUU 3903
X
CGAA AUUCAGAA CAGAUGAA
1972 GUUCAUCU CUGAUGAG 2765 UCUGAAUUC 3904
X
30
CGAA AAUUCAGA AGAUGAAC
1992 AUCAAUAU CUGAUGAG 2766 AGACAGCUC 3905
X
CGAA AGCUGUCU AUAUUGAU
1995 AACAUCAA CUGAUGAG 2767 CAGCUCAUA 3906
X
CGAA AUGAGCUG UUGAUGUU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99106507
161
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
1997 UGAACAUC CUC3AUGAG2768 GCUCAUAUU 3907
X
CGAA AUAUGAGC GAUGUUCA
2003 AAGAAGUG CUGAUGAG 2769 AUUGAUGUU 3908
X
CGAA ACAUCAAU CACUUCUU
2004 UAAGAAGU CUGAUGAG 2770 UUGAUGUUC 3909
X
CGAA AACAUCAA ACUUCUUA
2008 CUUUUAAG CUGAUGAG 2771 UGUUCACUU 3910
X
CGAA AGUGAACA CUUAAAAG
2009 UCUUUUAA CUGAUGAG 2772 GUUCACUUC 3911
X
CGAA AAGUGAAC UUAAAAGA
2011 CCUCUUUU CUGAUGAG 2773 UCACUUCUU 3912
X
CGAA AGAAGUGA AAAAGAGG
2012 CCCUCUUU CUGAUGAG 2779 CACUUCUUA 3913
X
CGAA AAGAAGUG AAAGAGGG
2039 CUGUUACA CUGAUGAG 2775 GACAAUGUA 3914
X
CGAA ACAUUGUC UGUAACAG
2043 GUUGCUGU CUGAUGAG 2776 AUGUAUGUA 3915
X
CGAA ACAUACAU ACAGCAAC
2054 UCUAGUUU CUGAUGAG 2777 AGCAACCUU 3916
X
CGAA AGGUUGCU AAACUAGA
2055 UUCUAGUU CUGAUGAG 2?78 GCAACCUUA 3917
X
CGAA AAGGUUGC AACUAGAA
2060 UUAUAUUC CUGAUGAG 2779 CUUAAACUA 3918
X
CGAA AGUUUAAG GAAUAUAA
2065 AAAAUUUA CUGAUGAG 2780 ACUAGAAUA 3919
X
CGAA AUUCUAGU UAAAUUUU
2067 GCAAAAUU CUGAUGAG 2781 UAGAAUAUA 3920
X
CGAA AUAUUCUA AAUUUUGC
2071 GGGUGCAA CUGAUGAG 2782 AUAUAAAUU 3921
X
CGAA AUUUAUAU UUGCACCC
2072 CGGGUGCA CUGAUGAG 2783 UAUAAAUUU 3922
X
CGAA AAUUUAUA UGCACCCG
CA 02324421 2000-09-26
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162
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
2073 UCGGGUGC CUGAUGAG 2789 AUAAAUUUU 3923
X
CGAA AAAUUUAU GCACCCGA
2091 UUUGUCUU CUGAUGAG 2785 AAGGAAAUC 3924
X
CGAA AUUUCCUU ~ AAGACAAA
2101 AAUAAGAA CUGAUGAG 2786 AGACAAAUU 3925
X
CGAA AUUUGUCU UUCUUAUU
2102 AAAUAAGA CUGAUGAG 2787 GACAAAUUU 3926
X
CGAA AAUUUGUC UCUUAUUU
2103 UAAAUAAG CUGAUGAG 2788 ACAAAUUUU 3927
X
CGAA AAAUUUGU CUUAUUUA
2109 GUAAAUAA CUGAUGAG 2789 GAAAUUUUC 3928
X
CGAA AAAAUUUG UUAUUUAC
2106 UGGUAAAU CUGAUGAG 2790 AAUUUUCUU 3929
X
CGAA AGAAAAUU AUUUACCA
2107 UUGGUAAA CUGAUGAG 2791 AUUUUCUUA 3930
X
CGAA AAGAAAAU UUUACCAA
2109 AAUUGGUA CUGAUGAG 2792 UUUCUUAUU 3931
X
2 O CGAA AUAAGAAA UACCAAUU
2110 GAAUUGGU CUGAUGAG 2793 UUCUUAUUU 3932
X
CGAA AAUAAGAA ACCAAUUC
2111 UGAAUUGG CUGAUGAG 2794 UCUUAUUUA 3933
X
CGAA AAAUAAGA CCAAUUCA
7
5
2117 CCUUUUUG CUGAUGAG 2 UUACCAAUU 3934
X 9
CGAA AUUGGUAA CAAAAAGG
2118 ACCUUUUU CUGAUGAG 2796 UACCAAUUC 3935
X
CGAA AAUUGGUA AAAAAGGU
2129 AGUUCUGG CUGAUGAG 2797 AAAGGUGUA 3936
X
CGAA ACACCUUU CCAGAACU
2138 UUUAGAAC CUGAUGAG 2798 CCAGAACUA 3937
X
CGAA AGUUCUGG GUUCUAAA
2191 UCUUUUAG CUGAUGAG 2799 GAACUAGUU 3938
X
CGAA ACUAGUUC CUAAAAGA
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
163
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
2192 AUCUUUUA CUGAUGAG 2800 AACUAGUUC 3939
X
CGAA AACUAGUU UAAAAGAU
2149 UGAUCUUU CUGAUGAG 2801 CUAGUUCUA 3940
X
CGAA AGAACUAG AAAGAUCA
2151 AUCCUUCU CUGAUGAG 2802 UAAAAGAUC 3941
X
CGAA AUCUUUUA AGAAGGAU
2160 UAAAGCAA CUGAUGAG 2803 AGAAGGAUA 3992
X
CGAA AUCCUUCU UUGCUUUA
2162 UCUAAAGC CUGAUGAG 2804 AAGGAUAUU 3943
X
CGAA AUAUCCUU GCUUUAGA
2166 UAUUUCUA CUGAUGAG 2805 AUAUUGCUU 3944
X
CGAA AGCAAUAU UAGAAAUA
2167 UUAUUUCU CUGAUGAG 2806 UAUUGCUUU 3945
X
CGAA AAGCAAUA AGAAAUAA
2168 GUUAUUUC CUGAUGAG 2807 AUUGCUUUA 3996
X
CGAA AAAGCAAU GAAAUAAC
2179 GUCACUGU CUGAUGAG 2808 UUAGAAAUA 3947
X
2 0 CGAA AUUUCUAA ACAGUGAC
2193 UGGGUUGG CUGAUGAG 2809 ACAGCCCUU 3948
X
CGAA AGGGCUGU CCAACCCA
2194 UUGGGUUG CUGAUGAG 2810 CAGCCCUUC 3949
X
CGAA AAGGGCUG CAACCCAA
2208 UUUUGUGG CUGAUGAG 2811 CAAGGAAUC 3950
X
CGAA AUUCCUUG CCACAAAA
2241 AAUCAGUU CUGAUGAG 2812 AUGAGGCUA 3951
X
CGAA AGCCUCAU AACUGAUU
2249 AACGUUGC CUGAUGAG 2813 AAACUGAUU 3952
X
CGAA AUCAGUUU GCAACGUU
2257 UGUCUGGA CUGAUGAG 2814 UGCAACGUU 3953
X
CGAA ACGUUGCA UCCAGACA
2258 GUGUCUGG CUGAUGAG 2815 GCAACGUUU 3954
X
CGAA AACGUUGC CCAGACAC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
164
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2259 AGUGUCUG CUGAUGAG 2816 CAACGUUUC 3955
X
CGAA AAACGUUG CAGACACU
2268 AUAGGUUA CUGAUGAG 2817 CAGACACUU 3956
X
CGAA AGUGUCUG UAACCUAU
2269 AAUAGGUU CUGAUGAG 2818 AGACACUUU 3957
X
CGAA AAGUGUCU AACCUAUU
2270 GAAUAGGU CUGAUGAG 2819 GACACUUUA 3958
X
CGAA AAAGUGUC ACCUAUUC
2275 AUGCAGAA CUGAUGAG 2820 UUUAACCUA 3959
X
CGAA AGGUUAAA UUCUGCAU
2277 AUAUGCAG CUGAUGAG 2821 UAACCUAUU 3960
X
CGAA AUAGGUUA CUGCAUAU
2278 UAUAUGCA CUGAUGAG 2822 AACCUAUUC 3961
X
CGAA AAUAGGUU UGCAUAUA
2284 GUUCUCUA CUGAUGAG 2823 UUCUGCAUA 3962
X
CGAA AUGCAGAA UAGAGAAC
2286 CAGUUCUC CUGAUGAG 2824 CUGCAUAUA 3963
X
CGAA AUAUGCAG GAGAACUG
2301 CUCAGGGA CUGAUGAG 2825 UGAGGGCUU 3964
X
CGAA AGCCCUCA UCCCUGAG
2302 UCUCAGGG CUGAUGAG 2826 GAGGGCUUU 3965
X
CGAA AAGCCCUC CCCUGAGA
2 5
2303 UUCUCAGG CUGAUGAG 2827 AGGGCUUUC 3966
X
CGAA AAAGCCCU CCUGAGAA
2317 CACAACUC CUGAUGAG 2828 GAAACAGUU 3967
X
CGAA ACUGUUUC GAGUUGUG
2322 GGCAACAC CUGAUGAG 2829 AGUUGAGUU 3968
X
CGAA ACUCAACU GUGUUGCC
2327 UGGUUGGC CUGAUGAG 2830 AGUUGUGUU 3969
X
CGAA ACACAACU GCCAACCA
2344 CAGCUUGC CUGAUGAG 2831 GAAUGGCUC 3970
X
CGAA AGCCAUUC GCAAGCUG
CA 02324421 2000-09-26
WO 99/50403 PGT/US99/06507
165
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2363 GGAUUUCC CUGAUGAG 2832 UGUGAGCUC 3971
X
CGAA AGCUCACA GGAAAUCC
2370 UUUAAAAG CUGAUGAG 2833 UCGGAAAUC 3972
X
CGAA AUUUCCGA CUUUUAAA
2373 UCUUUUAA CUGAUGAG 2834 GAAAUCCUU 3973
X
CGAA AGGAUUUC UUAAAAGA
2374 UUCUUUUA CUGAUGAG 2835 AAAUCCUUU 39?4
X
CGAA AAGGAUUU UAAAAGAA
2375 UUUCUUUU CUGAUGAG 2836 AAUCCUUUU 3975
X
CGAA AAAGGAUU AApAG~
2376 AUUUCUUU CUGAUGAG 2837 AUCCUUUUA 3976
X
CGAA AAAAGGAU AAAGAAAU
2385 GACAUUUG CUGAUGAG 2838 AAAGAAAUU 3977
X
CGAA AUUUCUUU CAAAUGUC
2386 UGACAUUU CUGAUGAG 2839 AAGAAAUUC 3978
X
CGAA AAUUUCUU AAAUGUCA
2393 UAAAAAGU CUGAUGAG 2840 UCAAAUGUC 3979
X
CGAA ACAUUUGA ACUUUUUA
2397 CAAAUAAA CUGAUGAG 2841 AUGUCACUU 3980
X
CGAA AGUGACAU UUUAUUUG
2398 CCAAAUAA CUGAUGAG 2842 UGUCACUUU 3981
X
CGAA AAGUGACA UUAUUUGG
2 5
2399 ACCAAAUA CUGAUGAG 2843 GUCACUUUU 3982
X
CGAA AAAGUGAC UAUUUGGU
2400 AACCAAAU CUGAUGAG 2849 UCACUUUUU 3983
X
CGAA AAAAGUGA AUUUGGUU
2901 AAACCAAA CUGAUGAG 2845 CACUUUUUA 3984
X
CGAA AAAAAGUG UUUGGUUU
2403 UAAAACCA CUGAUGAG 2846 CUUUUUAUU 3985
X
CGAA AUAAAAAG UGGUUUUA
2409 UUAAAACC CUGAUGAG 2897 UUUUUAUUU 3986
X
CGAA AAUAAAAA GGUUUUAA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
166
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
2908 GUACUUAA CUGAUGAG 2848 UAUUUGGUU 3987
X
CGAA ACCAAAUA UUAAGUAC
2409 UGUACUUA CUGAUGAG 2899 AUUUGGUUU 3988
X
CGAA AACCAAAU UAAGUACA
2910 UUGUACUU CUGAUGAG 2850 UUUGGUUUU 3989
X
CGAA AAACCAAA AAGUACAA
2411 GUUGUACU CUGAUGAG 2851 UUGGUUUUA 3990
X
CGAA AAAACCAA AGUACAAC
2915 UUCAGUUG CUGAUGAG 2852 UUUUAAGUA 3991
X
CGAA ACUUAAAA CAACUGAA
2426 UCAAAGGU CUGAUGAG 2853 ACUGAAGUC 3992
X
CGAA ACUUCAGU ACCUUUGA
2431 GGGUGUCA CUGAUGAG 2859 AGUCACCUU 3993
X
CGAA AGGUGACU UGACACCC
2432 GGGGUGUC CUGAUGAG 2855 GUCACCUUU 3999
X
CGAA AAGGUGAC GACACCCC
2443 UAUCCAGA CUGAUGAG 2856 CACCCCAUA 3995
X
2 O CGAA AUGGGGUG UCUGGAUA
2495 AAUAUCCA CUGAUGAG 2857 CCCCAUAUC 3996
X
CGAA AUAUGGGG UGGAUAUU
2451 CAGAUUAA CUGAUGAG 2858 AUCUGGAUA 3997
X
, CGAA AUCCAGAU UUAAUCUG
2453 UUCAGAUU CUGAUGAG 2859 CUGGAUAUU 3998
X
CGAA AUAUCCAG AAUCUGAA
2954 CUUCAGAU CUGAUGAG 2860 UGGAUAUUA 3999
X
CGAA AAUAUCCA AUCUGAAG
2457 UAACUUCA CUGAUGAG 2861 AUAUUAAUC 4000
X
CGAA AUUAAUAU UGAAGUUA
2464 UUGUUUCU CUGAUGAG 2862 UCUGAAGUU 4001
X
CGAA ACUUCAGA P .GAAACAA
2465 GUUGUUUC CUGAUGAG 2863 CUGAAGUUA 9002
X
CGAA AACUUCAG GAAACAAC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
167
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2481 AUUAUCUU CUGAUGAG 2864 CAAGCAAUC 4003
X
CGAA AUUGCUUG AAGAUAAU
2487 AGCCAAAU CUGAUGAG 2865 AUCAAGAUA 4004
X
CGAA AUCUUGAU AUUUGGCU
2990 UGGAGCCA CUGAUGAG 2866 AAGAUAAUU 4005
X
CGAA AUUAUCUU UGGCUCCA
2491 UUGGAGCC CUGAUGAG 2867 AGAUAAUUU 4006
X
CGAA AAUUAUCU GGCUCCAA
2496 UGUAAUUG CUGAUGAG 2868 AUUUGGCUC 4007
X
CGAA AGCCAAAU CAAUUACA
2501 UUAGCUGU CUGAUGAG 2869 GCUCCAAUU 9008
X
CGAA AUUGGAGC ACAGCUAA
2502 UUUAGCUG CUGAUGAG 2870 CUCCAAUUA 4009
X
CGAA AAUUGGAG CAGCUAAA
2508 UUUUGCUU CUGAUGAG 2871 UUACAGCUA 9010
X
CGAA AGCUGUAA AAGCAAAA
2522 AGUUCAAU CUGAUGAG 2872 AAAGUGGUU 4011
X
CGAA ACCACUUU AUUGAACU
2523 CAGUUCAA CUGAUGAG 2873 AAGUGGUUA 4012
X
CGAA AACCACUU UUGAACUG
2525 AGCAGUUC CUGAUGAG 2874 GUGGUUAUU 9013
X
CGAA AUAACCAC GAACUGCU
2539 ACCGAUAA CUGAUGAG 2875 GAACUGCUU 4014
X
CGAA AGCAGUUC UUAUCGGU
2535 GACCGAUA CUGAUGAG 2876 AACUGCUUU 4015
X
CGAA AAGCAGUU UAUCGGUC
2536 AGACCGAU CUGAUGAG 2877 ACUGCUUUU 4016
X
CGAA AAAGCAGU AUCGGUCU
2537 GAGACCGA CUGAUGAG 2878 CUGCUUUUA 4017
X
CGAA AAAAGCAG UCGGUCUC
2539 CCGAGACC CUGAUGAG 2879 GCUUUUAUC 4018
X
CGAA AUAAAAGC GGUCUCGG
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
168
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
2593 ACUCCCGA CUGAUGAG 2880 UUAUCGGUC 4019
X
CGAA ACCGAUAA UCGGGAGU
2545 CAACUCCC CUGAUGAG 2881 AUCGGUCUC 4020
X
CGAA AGACCGAU GGGAGUUG
2552 GGUUUAGC CUGAUGAG 2882 UCGGGAGUU 4021
X
CGAA ACUCCCGA GCUAAACC
2556 GGAAGGUU CUGAUGAG 2883 GAGUUGCUA 4022
X
CGAA AGCAACUC AACCUUCC
2562 CACCUGGG CUGAUGAG 2884 CUAAACCUU 4023
X
CGAA AGGUUUAG CCCAGGUG
2563 ACACCUGG CUGAUGAG 2885 UAAACCUUC 9024
X
CGAA AAGGUUUA CCAGGUGU
2572 CUCCAAAA CUGAUGAG 2886 CCAGGUGUA 4025
X
CGAA ACACCUGG UUUUGGAG
2579 ACCUCCAA CUGAUGAG 2887 AGGUGUAUU 4026
X
CGAA AUACACCU UUGGAGGU
2575 UACCUCCA CUGAUGAG 2888 GGUGUAUUU 4027
X
CGAA AAUACACC UGGAGGUA
2576 GUACCUCC CUGAUGAG 2889 GUGUAUUUU 9028
X
CGAA AAAUACAC GGAGGUAC
2583 AACAACUG CUGAUGAG 2890 UUGGAGGUA 4029
X
CGAA ACCUCCAA CAGUUGUU
2588 UCGCCAAC CUGAUGAG 2891 GGUACAGUU 4030
X
CGAA ACUGUACC GUUGGCGA
2591 UGCUCGCC CUGAUGAG 2892 ACAGUUGUU 4031
X
CGAA ACAACUGU GGCGAGCA
2609 AGAUUUCA CUGAUGAG 2893 AGCAAGCUA 4032
X
CGAA AGCUUGCU UGAAAUCU
2611 CAUCUUCA CUGAUGAG 2894 UAUGAAAUC 4033
X
CGAA AUUUCAUA UGAAGAUG
2631 CUCUAUUA CUGAUGAG 2895 UGGGAAGUU 9034
X
CGAA ACUUCCCA UAAUAGAG
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/0650'I
169
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
2632 ACUCUAUU CUGAUGAG 2896 GGGAAGUUU 4035
X
CGAA AACUUCCC AAUAGAGU
2633 UACUCUAU CUGAUGAG 2897 GGAAGUUUA 4036
X
CGAA AAACUUCC AUAGAGUA
2636 UCAUACUC CUGAUGAG 2898 AGUUUAAUA 4037
X
CGAA AUUAAACU GAGUAUGA
2641 UGAAUUCA CUGAUGAG 2899 AAUAGAGUA 9038
X
CGAA ACUCUAUU UGAAUUCA
2647 UUACCCUG CUGAUGAG 2900 GUAUGAAUU 4039
X
CGAA AUUCAUAC CAGGGUAA
2648 AUUACCCU CUGAUGAG 2901 UAUGAAUUC 9090
X
CGAA AAUUCAUA AGGGUAAU
2659 AAGUUUAU CUGAUGAG 2902 UUCAGGGUA 9041
X
CGAA ACCCUGAA AUAAACUU
2657 CCUAAGUU CUGAUGAG 2903 AGGGUAAUA 4042
X
CGAA AUUACCCU AACUUAGG
2662 GUUUACCU CUGAUGAG 2904 AAUAAACUU 4043
X
CGAA AGUUUAUU AGGUAAAC
2663 GGUUUACC CUGAUGAG 2905 AUAAACUUA 4044
X
CGAA AAGUUUAU GGUAAACC
2667 AAGAGGUU CUGAUGAG 2906 ACUUAGGUA 9045
X
CGAA ACCUAAGU AACCUCUU
2673 GUUUGUAA CUGAUGAG 2907 GUAAACCUC 4046
X
CGAA AGGUUUAC UUACAAAC
2675 AGGUUUGU CUGAUGAG 2908 AAACCUCUU 4047
X
CGAA AGAGGUUU ACAAACCU
2676 GAGGUUUG CUGAUGAG 2909 AACCUCUUA 4098
X
CGAA AAGAGGUU CAAACCUC
2684 GCUGUGCC CUGAUGAG 2910 ACAAACCUC 9099
X
CGAA AGGUUUGU GGCACAGC
2698 GAAUGUUC CUGAUGAG 2911 AGCAACCUU 4050
X
CGAA AGGUUGCU GAACAUUC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
170
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
2705 GGCCACUG CUGAUGAG 2912 UUGAACAUU 4051
X
CGAA AUGUUCAA CAGUGGCC
2706 UGGCCACU CUGAUGAG 2913 UGAACAUUC 4052
X
CGAA AAUGUUCA AGUGGCCA
2723 CCAUUGCU CUGAUGAG 2914 AAAGAAAUU 4053
X
CGAA AUUUCUUU AGCAAUGG
2724 CCCAUUGC CUGAUGAG 2915 AAGAAAUUA 4054
X
CGAA AAUUUCUU GCAAUGGG
2740 AAUAAAGC CUGAUGAG 2916 GAAAUGGUU 4055
X
CGAA ACCAUUUC GCUUUAUU
2744 ACCAAAUA CUGAUGAG 2917 UGGUUGCUU 4056
X
CGAA AGCAACCA UAUUUGGU
2745 CACCAAAU CUGAUGAG 2918 GGUUGCUUU 4057
X
CGAA AAGCAACC AUUUGGUG
2746 UCACCAAA CUGAUGAG 2919 GUUGCUUUA 4058
X
CGAA AAAGCAAC UUUGGUGA
2748 UUUCACCA CUGAUGAG 2920 UGCUUUAUU 4059
X
CGAA AUAAAGCA UGGUGAAA
2799 CUUUCACC CUGAUGAG 2921 GCUUUAUUU 9060
X
CGAA AAUAAAGC GGUGAAAG
2759 UUGGAUUC CUGAUGAG 2922 GUGAAAGUA 4061
X
CGAA ACUUUCAC GAAUCCAA
2764 AUCCUUUG CUGAUGAG 2923 AGUAGAAUC 4062
X
CGAA AUUCUACU CAAAGGAU
2773 CCUUUUCC CUGAUGAG 2924 CAAAGGAUU 4063
X
CGAA AUCCUUUG GGAAAAGG
2783 UCACAAGU CUGAUGAG 2925 GAAAAGGUA 4064
X
CGAA ACCUUUUC ACUUGUGA
2787 UGGCUCAC CUGAUGAG 2926 AGGUAACUU 9065
X
CGAA AGUUACCU GUGAGCCA
2807 AGGGAGUU CUGAUGAG 2927 AAGGAGAUA 4066
X
CGAA AUCUCCUU AACUCCCU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
171
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
2812 GGUUCAGG CUGAUGAG 2928 GAUAAACUC 4067
X
CGAA AGUUUAUC CCUGAACC
2822 GACUCCGU CUGAUGAG 2929 CUGAACCUA 4068
X
CGAA AGGUUCAG ACGGAGUC
2830 AGUUGUGA CUGAUGAG 2930 AACGGAGUC 4069
X
CGAA ACUCCGUU UCACAACU
2832 UGAGUUGU CUGAUGAG 2931 CGGAGUCUC 4070
X
CGAA AGACUCCG ACAACUCA
2839 UCUUUCUU CUGAUGAG 2932 UCACAACUC 4071
X
CGAA AGUUGUGA AAGAAAGA
2858 UUUUCAGU CUGAUGAG 2933 CGGGAAAUU 4072
X
CGAA AUUUCCCG ACUGAAAA
2859 UUUUUCAG CUGAUGAG 2934 GGGAAAUUA 4073
X
CGAA AAUUUCCC CUGAAAAA
2873 UUAUCAUC CUGAUGAG 2935 AAACAGAUA 4074
X
CGAA AUCUGUUU GAUGAUAA
2880 UUUUCUGU CUGAUGAG 2936 UAGAUGAUA 4075
X
2 O CGAA AUCAUCUA ACAGAAAA
2890 AUAAAGAA CUGAUGAG 2937 CAGAAAAUU 4076
X
CGAA AUUUUCUG UUCUUUAU
2891 AAUAAAGA CUGAUGAG 2938 AGAAAAUUU 4077
X
CGAA AAUUUUCU UCUUUAUU
2892 AAAUAAAG CUGAUGAG 2939 GAAAAUUUU 4078
X
CGAA AAAUUUUC CUUUAUUU
2893 CAAAUAAA CUGAUGAG 2940 AAAAUUUUC 4079
X
CGAA AAAAUUUU UUUAUUUG
2895 AGCAAAUA CUGAUGAG 2941 AAUUUUCUU 4080
X
CGAA AGAAAAUU UAUUUGCU
2896 CAGCAAAU CUGAUGAG 2942 AUUUUCUUU 4081
X
CGAA AAGAAAAU AUUUGCUG
2897 UCAGCAAA CUGAUGAG 2943 UUUUCUUUA 4082
X
GGAA AAAGAAAA UUUGCUGA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
172
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
2899 UUUCAGCA CUGAUGAG 2944 UUCUUUAUU 4083
X
CGAA AUAAAGAA UGCUGAAA
2900 CUUUCAGC CUGAUGAG 2945 UCUUUAUUU 4089
X
CGAA AAUAAAGA GCUGAAAG
2919 GAGUCUGG CUGAUGAG 2946 AAGAAAAUA 4085
X
CGAA AUUUUCUU CCAGACUC
2922 ACAGUUAA CUGAUGAG 2997 ACCAGACUC 4086
X
CGAA AGUCUGGU UUAACUGU
2924 CUACAGUU CUGAUGAG 2998 CAGACUCUU 4087
X
CGAA AGAGUCUG AACUGUAG
2925 GCUACAGU CUGAUGAG 2949 AGACUCUUA 9088
X
CGAA AAGAGUCU ACUGUAGC
2931 GUUCACGC CUGAUGAG 2950 UUAACUGUA 4089
X
CGAA ACAGUUAA GCGUGAAC
2957 GGGCAUCU CUGAUGAG 2951 GUGAACAUC 9090
X
CGAA AUGUUCAC AGAUGCCC
2992 AAAUAAGA CUGAUGAG 2952 CAAGGCGUC 4091
X
CGAA ACGCCUUG UCUUAUUU
2994 CAAAAUAA CUGAUGAG 2953 AGGCGUCUC 4092
X
CGAA AGACGCCU UUAUUUUG
2996 CGCAAAAU CUGAUGAG 2954 GCGUCUCUU 9093
X
CGAA AGAGACGC AUUUUGCG
2 5
2997 GCGCAAAA CUGAUGAG 2955 CGUCUCUUA 4094
X
CGAA AAGAGACG UUUUGCGC
2999 GAGCGCAA CUGAUGAG 2956 UCUCUUAUU 4095
X
CGAA AUAAGAGA UUGCGCUC
3000 CGAGCGCA CUGAUGAG 2957 CUCUUAUUU 4096
X
CGAA AAUAAGAG UGCGCUCG
3001 UCGAGCGC CUGAUGAG 2958 UCUUAUUUU 9097
X
CGAA AAAUAAGA GCGCUCGA
3007 AUAACCUC CUGAUGAG 2959 UUUGCGCUC 9098
X
CGAA AGCGCAAA GAGGUUAU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
173
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3013 UGUUCCAU CUGAUGAG 2960 CUCGAGGUU 4099
X
CGAA ACCUCGAG AUGGAACA
309 CUGUUCCA CUGAUGAG 2961 UCGAGGUUA 9100
X
CGAA AACCUCGA UGGAACAG
3028 CCUCUAGA CUGAUGAG 2962 CAGCACAUU 4101
X
CGAA AUGUGCUG UCUAGAGG
3029 UCCUCUAG CUGAUGAG 2963 AGCACAUUU 4102
X
CGAA AAUGUGCU CUAGAGGA
3030 UUCCUCUA CUGAUGAG 2964 GCACAUUUC 9103
X
CGAA AAAUGUGC UAGAGGAA
3032 UAUUCCUC CUGAUGAG 2965 ACAUUUCUA 4109
X
CGAA AGAAAUGU GAGGAAUA
3040 GUUUGGAA CUGAUGAG 2966 AGAGGAAUA 9105
X
CGAA AUUCCUCU UUCCAAAC
3042 CAGUUUGG CUGAUGAG 2967 AGGAAUAUU 4106
X
CGAA AUAUUCCU CCAAACUG
3093 UCAGUUUG CUGAUGAG 2968 GGAAUAUUC 4107
X
2 O CGAA AAUAUUCC CAAACUGA
3055 UGUCCAAG CUGAUGAG 2969 ACUGAACUA 4108
X
CGAA AGUUCAGU CUUGGACA
3058 GAAUGUCC CUGAUGAG 2970 GAACUACUU 4109
X
CGAA AGUAGUUC GGACAUUC
3065 CGCAUGAG CUGAUGAG 2971 UUGGACAUU 4110
X
CGAA AUGUCCAA CUCAUGCG
3066 UCGCAUGA CUGAUGAG 2972 UGGACAUUC 9111
X
CGAA AAUGUCCA UCAUGCGA
3068 GCUCGCAU CUGAUGAG 2973 GACAUUCUC 4112
X
CGAA AGAAUGUC AUGCGAGC
3079 CAUCAAUG CUGAUGAG 2979 GCGAGCCUU 4113
X
CGAA AGGCUCGC CAUUGAUG
3080 ACAUCAAU CUGAUGAG 2975 CGAGCCUUC 4119
X
CGAA AAGGCUCG AUUGAUGU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
174
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3083 GUCACAUC CUGAUGAG 2976 GCCUUCAUU 4115
X
CGAA AUGAAGGC GAUGUGAC
3108 CAGCCUGA CUGAUGAG 2977 CCGAAAAUA 4116
X
CGAA AUUUUCGG UCAGGCUG
3110 GGCAGCCU CUGAUGAG 2978 GAAAAUAUC 9117
X
CGAA AUAUUUUC AGGCUGCC
3132 UCGAACCU CUGAUGAG 2979 CAGGCACUC 4118
X
CGAA AGUGCCUG AGGUUCGA
3137 GUCACUCG CUGAUGAG 2980 ACUCAGGUU 4119
X
CGAA ACCUGAGU CGAGUGAC
3138 AGUCACUC CUGAUGAG 2981 CUCAGGUUC 4120
X
CGAA AACCUGAG GAGUGACU
3151 UUGAGGGA CUGAUGAG 2982 GACUGUGUU 4121
X
CGAA ACACAGUC UCCCUCAA
3152 UUUGAGGG CUGAUGAG 2983 ACUGUGUUU 4122
X
CGAA AACACAGU CCCUCAAA
3153 CUUUGAGG CUGAUGAG 2989 CUGUGUUUC 4123
X
2 O CGAA AAACACAG CCUCAAAG
3157 CAGUCUUU CUGAUGAG 2985 GUUUCCCUC 4124
X
CGAA AGGGAAAC AAAGACUG
3167 UACUGAGC CUGAUGAG 2986 AAGACUGUA 4125
X
CGAA ACAGUCUU GCUCAGUA
3171 CGAAUACU CUGAUGAG 2987 CUGUAGCUC 4126
X
CGAA AGCUACAG AGUAUUCG
3175 CUCCCGAA CUGAUGAG 2988 AGCUCAGUA 4127
X
CGAA ACUGAGCU UUCGGGAG
3177 UACUCCCG CUGAUGAG 2989 CUCAGUAUU 9128
X
CGAA AUACUGAG CGGGAGUA
3178 GUACUCCC CUGAUGAG 2990 UCAGUAUUC 4129
X
CGAA AAUACUGA GGGAGUAC
3185 CACCAAGG CUGAUGAG 2991 UCGGGAGUA 4130
X
CGAA ACUCCCGA CCUUGGUG
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
175
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3189 GAUCCACC CUGAUGAG 2992 GAGUACCUU 4131
X
CGAA AGGUACUC GGUGGAUC
3197 ACUAGGAU CUGAUGAG 2993 UGGUGGAUC 4132
X
CGAA AUCCACCA AUCCUAGU
3200 GCCACUAG CUGAUGAG 2999 UGGAUCAUC 4133
X
CGAA AUGAUCCA CUAGUGGC
3203 AUAGCCAC CUGAUGAG 2995 AUCAUCCUA 9139
X
CGAA AGGAUGAU GUGGCUAU
3210 AGCGAGAA CUGAUGAG 2996 UAGUGGCUA 4135
X
CGAA AGCCACUA UUCUCGCU
3212 CCAGCGAG CUGAUGAG 2997 GUGGCUAUU 4136
X
CGAA AUAGCCAC CUCGCUGG
3213 CCCAGCGA CUGAUGAG 2998 UGGCUAUUC 9137
X
CGAA AAUAGGCA UCGCUGGG
3215 AUCCCAGC CUGAUGAG 2999 GCUAUUCUC 9138
X
CGAA AGAAUAGC GCUGGGAU
3224 AGCAUCAA CUGAUGAG 3000 GCUGGGAUC 9139
X
CGAA AUCCCAGC UUGAUGCU
3226 CAAGCAUC CUGAUGAG 3001 UGGGAUCUU 9140
X
CGAA AGAUCCCA GAUGCUUG
3233 AAUAAAGC CUGAUGAG 3002 UUGAUGCUU 9141
X
CGAA AGCAUCAA GCUUUAUU
3237 CACUAAUA CUGAUGAG 3003 UGCUUGCUU 4142
X
CGAA AGCAAGCA UAUUAGUG
3238 AGACUAAU CUGAUGAG 3004 GCUUGCUUU 9143
X
CGAA AAGCAAGC AUUAGUGU
3239 AACACUAA CUGAUGAG 3005 CUUGCUUUA 9149
X
CGAA AAAGCAAG UUAGUGUU
3241 UAAACACU CUGAUGAG 3006 UGCUUUAUU 4145
X
CGAA AUAAAGCA AGUGUUUA
3292 AUAAACAC CUGAUGAG 3007 GCUUUAUUA 4146
X
CGAA AAUAAAGC GUGUUUAU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
176
Seq. I.D. Seq. I.D.
Position RZ . No. Substrate No.
3297 AUAGUAUA CUGAUGAG 3008 AUUAGUGUU 4197
X
CGAA ACACUAAU UAUACUAU
3248 CAUAGUAU CUGAUGAG 3009 UUAGUGUUU 9148
X
CGAA AACACUAA AUACUAUG
3249 CCAUAGUA CUGAUGAG 3010 UAGUGUUUA 4149
X
CGAA AAACACUA UACUAUGG
3251 UUCCAUAG CUGAUGAG 3011 GUGUUUAUA 9150
X
CGAA AUAAACAC CUAUGGAA
3259 CACUUCCA CUGAUGAG 3012 UUUAUACUA 4151
X
CGAA AGUAUAAA UGGAAGUG
3267 CUUGAAGA CUGAUGAG 3013 AGUGUGGUU 9152
X
CGAA ACCACACU UCUUCAAG
3268 UCUUGAAG CUGAUGAG 3019 GUGUGGUUU 9153
X
CGAA AACCACAC CUUCAAGA
3269 CUCUUGAA CUGAUGAG 3015 UGUGGUUUC 9154
X
CGAA AAACCACA UUCAAGAG
3271 UUCUCUUG CUGAUGAG 3016 UGGUUUCUU 4155
X
CGAA AGAAACCA CAAGAGAA
3272 UUUCUCUU CUGAUGAG 3017 GGUUUCUUC 9156
X
CGAA AAGAAACC AAGAGAAA
3282 AUCUUUCU CUGAUGAG 3018 AGAGAAAUA 4157
X
CGAA AUUUCUCU AGAAAGAU
3291 AUCAUAAU CUGAUGAG 3019 AGAAAGAUC 4158
X
CGAA AUCUUUCU AUUAUGAU
3294 GGCAUCAU CUGAUGAG 3020 AAGAUCAUU 9159
X
CGAA AUGAUCUU AUGAUGCC
3295 UGGCAUCA CUGAUGAG 3021 AGAUCAUUA 4160
X
CGAA AAUGAUCU UGAUGCCA
3307 CCUUGUGA CUGAUGAG 3022 UGCCACAUA 4161
X
CGAA AUGUGGCA UCACAAGG
3309 AGCCUUGU CUGAUGAG 3023 CCACAUAUC 4162
X
CGAA AUAUGUGG ACAAGGCU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
177
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3323 UGAGCAUG CUGAUGAG 3024 GCUGAGAUC 4163
X
CGAA AUCUCAGC CAUGCUCA
3330 AGAUGGCU CUGAUGAG 3025 UCCAUGCUC 9164
X
CGAA AGCAUGGA AGCCAUCU
3337 CUUUAUCA CUGAUGAG 3026 UCAGCCAUC 9165
X
CGAA AUGGCUGA UGAUAAAG
3342 CCUCUCUU CUGAUGAG 3027 CAUCUGAUA 4166
X
CGAA AUCAGAUG AAGAGAGG
3353 UCAGAAGU CUGAUGAG 3028 GAGAGGCUU 4167
X
CGAA AGCCUCUC ACUUCUGA
3354 AUCAGAAG CUGAUGAG 3029 AGAGGCUUA 4168
X
CGAA AAGCCUCU CUUCUGAU
3357 UGCAUCAG CUGAUGAG 3030 GGCUUACUU 4169
X
CGAA AGUAAGCC CUGAUGCA
3358 AUGCAUCA CUGAUGAG 3031 GCUUACUUC 4170
X
CGAA AAGUAAGC UGAUGCAU
3367 AUCAAUAC CUGAUGAG 3032 UGAUGCAUA 9171
X
CGAA AUGCAUCA GUAUUGAU
3370 UAGAUCAA CUGAUGAG 3033 UGCAUAGUA 4172
X
CGAA ACUAUGCA UUGAUCUA
3372 AGUAGAUC CUGAUGAG 3039 CAUAGUAUU 4173
X
CGAA AUACUAUG GAUCUACU
3376 CAGAAGUA CUGAUGAG 3035 GUAUUGAUC 4174
X
CGAA AUCAAUAC UACUUCUG
3378 UACAGAAG CUGAUGAG 3036 AUUGAUCUA 9175
X
CGAA AGAUCAAU CUUCUGUA
3381 AAUUACAG CUGAUGAG 3037 GAUCUACUU 4176
X
CGAA AGUAGAUC CUGUAAUU
3382 CAAUUACA CUGAUGAG 3038 AUCUACUUC 4I7?
X
CGAA AAGUAGAU UGUAAUUG
3386 CACACAAU CUGAUGAG 3039 ACUUCUGUA 4178
X
CGAA ACAGAAGU AUUGUGUG
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
178
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3389 AUCCACAC CUGAUGAG 3040 UCUGUAAUU 4179
X
CGAA AUUACAGA GUGUGGAU
3398 GUUUAAAG CUGAUGAG 3041 GUGUGGAUU 9180
X
CGAA AUCCACAC CUUUAAAC
3399 CGUUUAAA CUGAUGAG 3042 UGUGGAUUC 4181
X
CGAA AAUCCACA UUUAAACG
3401 AGCGUUUA CUGAUGAG 3093 UGGAUUCUU 4182
X
CGAA AGAAUCCA UAAACGCU
3902 GAGCGUUU CUGAUGAG 3049 GGAUUCUUU 9183
X
CGAA AAGAAUCC AAACGCUC
3403 AGAGCGUU CUGAUGAG 3045 GAUUCUUUA 4184
X
CGAA AAAGAAUC AACGCUCU
I5 3410 CGUACCUA CUGAUGAG 3046 UAAACGCUC 4185
X
CGAA AGCGUUUA UAGGUACG
3412 AUCGUACC CUGAUGAG 3047 AACGCUCUA 9186
X
CGAA AGAGCGUU GGUACGAU
3416 UGUCAUCG CUGAUGAG 3098 CUCUAGGUA 4187
X
CGAA ACCUAGAG CGAUGACA
3429 UAUCGGGG CUGAUGAG 3099 GACAGUGUU 4188
X
CGAA ACACUGUC CCCCGAUA
3930 GUAUCGGG CUGAUGAG 3050 ACAGUGUUC 4189
X
CGAA AACACUGU CCCGAUAC
2 5
3437 CAGCAUGG CUGAUGAG 3051 UCCCCGAUA 4190
X
CGAA AUCGGGGA CCAUGCUG
3447 CGGAUCCU CUGAUGAG 3052 CAUGCUGUA 4191
X
CGAA ACAGCAUG AGGAUCCG
3453 UCUUUCCG CUGAUGAG 3053 GUAAGGAUC 4192
X
CGAA AUCCUUAC CGGAAAGA
3474 UCAUCUUU CUGAUGAG 3054 CGAGAGAUC 4193
X
CGAA AUCUCUCG AAAGAUGA
3488 UAUCAAUA CUGAUGAG 3055 UGAAAAGUA 4194
X
CGAA ACUUUUCA UAUUGAUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
179
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
3490 GUUAUCAA CUGAUGAG 3056 AAAAGUAUA 4195
X
CGAA AUACUUUU UUGAUAAC
3992 AGGUUAUC CUGAUGAG 3057 AAGUAUAUU 4196
X
CGAA AUAUACUU GAUAACCU
3496 UUCAAGGU CUGAUGAG 3058 AUAUUGAUA 4197
X
CGAA AUCAAUAU ACCUUGAA
3501 UUUUUUUC CUGAUGAG 3059 GAUAACCUU 4198
X
CGAA AGGUUAUC GAAAAAAA
3519 CACUUUGU CUGAUGAG 3060 CAGUGGAUC 4199
X
CGAA AUCCACUG ACAAAGUG
3595 GCUAUGAG CUGAUGAG 3061 UGAAAGCUA 4200
X
CGAA AGCUUUCA CUCAUAGC
3548 CCCGCUAU CUGAUGAG 3062 AAGCUACUC 4201
X
CGAA AGUAGCUU AUAGCGGG
3551 GCCCCCGC CUGAUGAG 3063 CUACUCAUA 4202
X
CGAA AUGAGUAG GCGGGGGC
3562 UUUUUUUU CUGAUGAG 3064 GGGGGCCUA 4203
X
2 0 CGAA AGGCCCCC F~AAAAAHA
3577 GUACUGUG CUGAUGAG 3065 AAAAAGCUU 4204
X
CGAA AGCUUUUU CACAGUAC
3578 GGUACUGU CUGAUGAG 3066 AAAAGCUUC 4205
X
CGAA AAGCUUUU ACAGUACC
2 5
3584 AGUUUGGG CUGAUGAG 3067 UUCACAGUA 4206
X
CGAA ACUGUGAA CCCAAACU
3596 GUUGGAAA CUGAUGAG 3068 AAACUGCUU 4207
X
CGAA AGCAGUUU UUUCCAAC
3597 AGUUGGAA CUGAUGAG 3069 AACUGCUUU 4208
X
30
CGAA AAGCAGUU UUCCAACU
3598 GAGUUGGA CUGAUGAG 3070 ACUGCUUUU 4209
X
CGAA AAAGCAGU UCCAACUC
3599 UGAGUUGG CUGAUGAG 3071 CUGCUUUUU 9210
X
CGAA AAAAGCAG CCAACUCA
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
180
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3600 CUGAGUUG CUGAUGAG 3072 UGCUUUUUC 4211
X
CGAA AAAAAGCA CAACUCAG
3606 GAAUUUCU CUGAUGAG 3073 UUCCAACUC 4212
X
CGAA AGUUGGAA AGAAAUUC
3613 CCAAAUUG CUGAUGAG 3079 UCAGAAAUU 9213
X
CGAA AUUUCUGA CAAUUUGG
3614 UCCAAAUU CUGAUGAG 3075 CAGAAAUUC 4214
X
CGAA AAUUUCUG AAUUUGGA
3618 UAAAUCCA CUGAUGAG 3076 AAUUCAAUU 4215
X
CGAA AUUGAAUU UGGAUUUA
3619 UUAAAUCC CUGAUGAG 3077 AUUCAAUUU 4216
X
CGAA AAUUGAAU GGAUUUAA
3629 GGCUUUUA CUGAUGAG 3078 AUUUGGAUU 4217
X
CGAA AUCCAAAU UAAAAGCC
3625 AGGCUUUU CUGAUGAG 3079 UUUGGAUUU 4218
X
CGAA AAUCCAAA AAAAGCCU
3626 CAGGCUUU CUGAUGAG 3080 UUGGAUUUA 4219
X
2 O CGAA AAAUCCAA AAAGCCUG
3637 CAGGGAUU CUGAUGAG 3081 AGCCUGCUC 4220
X
CGAA AGCAGGCU AAUCCCUG
3641 UCCUCAGG CUGAUGAG 3082 UGCUCAAUC 9221
X
CGAA AUUGAGCA CCUGAGGA
3655 CACUCUGA CUGAUGAG 3083 GGACUGAUU 4222
X
CGAA AUCAGUCC UCAGAGUG
3656 UCACUCUG CUGAUGAG 3089 GACUGAUUU 4223
X
CGAA AAUCAGUC CAGAGUGA
3657 GUCACUCU CUGAUGAG 3085 ACUGAUUUC 4224
X
CGAA AAAUCAGU AGAGUGAC
3667 ACUGUGUG CUGAUGAG 3086 GAGUGACUA 4225
X
CGAA AGUCACUC CACACAGU
3676 UAGGUUCG CUGAUGAG 3087 CACACAGUA 9226
X
CGAA ACUGUGUG CGAACCUA
CA 02324421 2000-09-26
WO 99/50403 PGTNS99/06507
181
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3684 UAAAACUG CUGAUGAG 3088 ACGAACCUA 4227
X
CGAA AGGUUCGU CAGUUUUA
3689 ACAGUUAA CUGAUGAG 3089 CCUACAGUU 4228
X
CGAA ACUGUAGG UUAACUGU
3690 CACAGUUA CUGAUGAG 3090 CUACAGUUU 4229
X
CGAA AACUGUAG UAACUGUG
3691 CCACAGUU CUGAUGAG 3091 UACAGUUUU 4230
X
CGAA AAACUGUA AACUGUGG
3692 UCCACAGU CUGAUGAG 3092 ACAGUUUUA 4231
X
CGAA AAAACUGU ACUGUGGA
3702 CGUAACAA CUGAUGAG 3093 CUGUGGAUA 4232
X
CGAA AUCCACAG UUGUUACG
3704 UACGUAAC CUGAUGAG 3094 GUGGAUAUU 4233
X
CGAA AUAUCCAC GUUACGUA
370? GGCUACGU CUGAUGAG 3095 GAUAUUGUU 4234
X
CGAA ACAAUAUC ACGUAGCC
3708 AGGGUACG CUGAUGAG 3096 AUAUUGUUA 4235
X
CGAA AACAAUAU CGUAGCCU
3712 CCUUAGGC CUGAUGAG 3097 UGUUACGUA 4236
X
CGAA ACGUAACA GCCUAAGG
3717 AGGAGCCU CUGAUGAG 3098 CGUAGCCUA 4237
X
CGAA AGGCUACG AGGCUCCU
3723 CAAAACAG CUGAUGAG 3099 CUAAGGCUC 4238
X
CGAA AGCCUUAG CUGUUUUG
3728 CUGUGCAA CUGAUGAG 3100 GCUCCUGUU 9239
X
CGAA ACAGGAGC UUGCACAG
3729 GCUGUGCA CUGAUGAG 3101 CUCCUGUUU 9290
X
CGAA AACAGGAG UGCACAGC
3730 GGCUGUGC CUGAUGAG 3102 UCCUGUUUU 4241
X
CGAA AAACAGGA GCACAGCC
3743 CAGUUUUA CUGAUGAG 3103 AGCCAAAUU 4242
X
CGAA AUUUGGCU UAAAACUG
CA 02324421 2000-09-26
WO 99/50403 PGT/US99/06507
182
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3749 ACAGUUUU CUGAUGAG 3109 GCCAAAUUU 4243
X
CGAA AAUUUGGC AAAACUGU
3745 AACAGUUU CUGAUGAG 3105 CCAAAUUUA 4244
X
CGAA AAAUUUGG AAACUGUU
3753 UCCAUUCC CUGAUGAG 3106 AAAACUGUU 4245
X
CGAA ACAGUUUU GGAAUGGA
3763 UAAAGAAA CUGAUGAG 3107 GAAUGGAUU 9296
X
CGAA AUCCAUUC UUUCUUUA
3769 UUAAAGAA CUGAUGAG 3108 AAUGGAUUU 9247
X
CGAA AAUCCAUU UUCUUUAA
3765 GUUAAAGA CUGAUGAG 3109 AUGGAUUUU 9248
X
CGAA AAAUCCAU UCUUUAAC
3766 AGUUAAAG CUGAUGAG 3110 UGGAUUUUU 9249
X
CGAA AAAAUCCA CUUUAACU
3767 CAGUUAAA CUGAUGAG 3111 GGAUUUUUC 4250
X
CGAA AAAAAUCC UUUAACUG
3769 GGCAGUUA CUGAUGAG 3112 AUUUUUCUU 4251
X
2 p CGAA AGAAAAAU UAACUGCC
3770 CGGCAGUU CUGAUGAG 3113 UUUUUCUUU 4252
X
CGAA AAGAAAAA AACUGCCG
3771 ACGGCAGU CUGAUGAG 3119 UUUUCUUUA 4253
X
CGAA AAAGAAAA ACUGCCGU
3780 AGUUAAAU CUGAUGAG 3115 ACUGCCGUA 4259
X
CGAA ACGGCAGU AUUUAACU
3783 GAAAGUUA CUGAUGAG 3116 GCCGUAAUU 4255
X
CGAA AUUACGGC UAACUUUC
3784 AGAAAGUU CUGAUGAG 3117 CCGUAAUUU 9256
X
CGAA AAUUACGG AACUUUCU
3785 CAGAAAGU CUGAUGAG 3118 CGUAAUUUA 4257
X
CGAA AAAUUACG ACUUUCUG
3789 AACCCAGA CUGAUGAG 3119 AUUUAACUU 4258
X
CGAA AGUUAAAU UCUGGGUU
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
183
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3790 CAACCCAG CUGAUGAG 3120 UUUAACUUU 9259
X
CGAA AAGUUAAA CUGGGUUG
3791 GCAACCCA CUGAUGAG 3121 UUAACUUUC 4260
X
CGAA AAAGUUAA UGGGUUGC
3797 ACAAAGGC CUGAUGAG 3122 UUCUGGGUU 9261
X
CGAA ACCCAGAA GCCUUUGU
3802 CAAAAACA CUGAUGAG 3123 GGUUGCCUU 4262
X
CGAA AGGCAACC UGUUUUUG
3803 CCAAAAAC CUGAUGAG 3124 GUUGCCUUU 9263
X
CGAA AAGGCAAC GUUUUUGG
3806 ACGCCAAA CUGAUGAG 3125 GCCUUUGUU 4264
X
CGAA ACAAAGGC UUUGGCGU
3807 CACGCCAA CUGAUGAG 3126 CCUUUGUUU 4265
X
CGAA AACAAAGG UUGGCGUG
3808 CCACGCCA CUGAUGAG 312? CUUUGUUUU 4266
X
CGAA AAACAAAG UGGCGUGG
3809 GCCACGCC CUGAUGAG 3128 UUUGUUUUU 4267
X
CGAA AAAACAAA GGCGUGGC
3823 CAUGAUGU CUGAUGAG 3129 GGCUGACUU 4268
X
CGAA AGUCAGCC ACAUCAUG
3824 ACAUGAUG CUGAUGAG 3130 GCUGACUUA 4269
X
CGAA AAGUCAGC CAUCAUGU
2 5
3828 CAACACAU CUGAUGAG 3131 ACUUACAUC 4270
X
CGAA AUGUAAGU AUGUGUUG
3835 CCUUCCCC CUGAUGAG 3132 UCAUGUGUU 4271
X
CGAA ACACAUGA GGGGAAGG
3855 CUGAGUGC CUGAUGAG 3133 UGCCCAGUU 4272
X
CGAA ACUGGGCA GCACUCAG
3861 UGUCACCU CUGAUGAG 3139 GUUGCACUC 9273
X
CGAA AGUGCAAC AGGUGACA
3871 AUCUGGAG CUGAUGAG 3135 GGUGACAUC 4274
X
CGAA AUGUCACC CUCCAGAU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/0650?
184
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3874 ACUAUCUG CUGAUGAG 3136 GACAUCCUC 4275
X
CGAA AGGAUGUC CAGAUAGU
3880 AGCUACAC CUGAUGAG 3137 CUCCAGAUA 4276
X
CGAA AUCUGGAG GUGUAGCU
3885 UCCUCAGC CUGAUGAG 3138 GAUAGUGUA 9277
X
CGAA ACACUAUC GCUGAGGA
3901 GGUGAGUG CUGAUGAG 3139 AGGCACCUA 4278
X
CGAA AGGUGCCU CACUCACC
3906 GUGCAGGU CUGAUGAG 3140 CCUACACUC 4279
X
CGAA AGUGUAGG ACCUGCAC
3916 CACUCUGU CUGAUGAG 3141 CCUGCACUA 4280
X
CGAA AGUGCAGG ACAGAGUG
3930 GAGGUUAG CUGAUGAG 3142 GUGGCCGUC 4281
X
CGAA ACGGCCAC CUAACCUC
3933 CCCGAGGU CUGAUGAG 3143 GCCGUCCUA 4282
X
CGAA AGGACGGC ACCUCGGG
3938 GCAGGCCC CUGAUGAG 3149 CCUAACCUC 9283
X
CGAA AGGUUAGG GGGCCUGC
3958 ACGUGAUG CUGAUGAG 3145 GCAGACGUC 4289
X
CGAA ACGUCUGC CAUCACGU
3962 GCUAACGU CUGAUGAG 3196 ACGUCCAUC 4285
X
CGAA AUGGACGU ACGUUAGC
2 5
3967 GGACAGCU CUGAUGAG 3147 CAUCACGUU 9286
X
CGAA ACGUGAUG AGCUGUCC
3968 GGGACAGC CUGAUGAG 3148 AUCACGUUA 9287
X
CGAA AACGUGAU GCUGUCCC
3979 UGAUGUGG CUGAUGAG 3149 UUAGCUGUC 4288
X
CGAA ACAGCUAA CCACAUCA
3981 AGUCUUGU CUGAUGAG 3150 UCCCACAUC 4289
X
CGAA AUGUGGGA ACAAGACU
3990 CAAUGGCA CUGAUGAG 3151 ACAAGACUA 9290
X
CGAA AGUCUUGU UGCCAUUG
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
185
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
3997 ACUACCCC CUGAUGAG 3152 UAUGCGAUU 4291
X
CGAA AUGGCAUA GGGGUAGU
4003 AACACAAC CUGAUGAG 3153 AUUGGGGUA 4292
X
CGAA ACCCCAAU GUUGUGUU
4006 UGAAACAC CUGAUGAG 3154 GGGGUAGUU 4293
X
CGAA ACUACCCC GUGUUUCA
4011 UCCGUUGA CUGAUGAG 3155 AGUUGUGUU 4294
X
CGAA ACACAACU UCAACGGA
4012 UUCCGUUG CUGAUGAG 3156 GUUGUGUUU 9295
X
CGAA AACACAAC CAACGGAA
4013 UUUCCGUU CUGAUGAG 3157 UUGUGUUUC 4296
X
CGAA AAACACAA AACGGAAA
4029 UAGUUUAA CUGAUGAG 3158 AGUGCUGUC 4297
X
CGAA ACAGCACU UUAAACUA
4031 UUUAGUUU CUGAUGAG 3159 UGCUGUCUU 4298
X
CGAA AGACAGCA AAACUAAA
9032 AUUUAGUU CUGAUGAG 3160 GCUGUCUUA 9299
X
CGAA AAGACAGC AACUAAAU
9037 UGCACAUU CUGAUGAG 3161 CUUAAACUA 4300
X
CGAA AGUUUAAG AAUGUGCA
4048 UCACCUUC CUGAUGAG 3162 UGUGCAAUA 4301
X
CGAA AUUGCACA GAAGGUGA
2 5
4060 AGGAUGGC CUGAUGAG 3163 GGUGAUGUU 9302
X
CGAA ACAUCACC GCCAUCCU
4066 GACGGUAG CUGAUGAG 3164 GUUGCCAUC 4303
X
CGAA AUGGCAAC CUACCGUC
4069 AAAGACGG CUGAUGAG 3165 GCCAUCCUA 4304
X
30
CGAA AGGAUGGC CCGUCUUU
4079 CAGGAAAA CUGAUGAG 3166 CCUACCGUC 9305
X
CGAA ACGGUAGG UUUUCCUG
4076 AACAGGAA CUGAUGAG 3167 UACCGUCUU 9306
X
CGAA AGACGGUA UUCCUGUU
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
186
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
9077 AAACAGGA CUGAUGAG 3168 ACCGUCUUU 4307
X
CGAA AAGACGGU UCCUGUUU
4078 GAAACAGG CUGAUGAG 3169 CCGUCUUUU 9308
X
CGAA AAAGACGG CCUGUUUC
4079 GGAAACAG CUGAUGAG 3170 CGUCUUUUC 4309
X
CGAA AAAAGACG CUGUUUCC
4084 AGCUAGGA CUGAUGAG 3171 UUUCCUGUU 9310
X
CGAA ACAGGAAA UCCUAGCU
4085 CAGCUAGG CUGAUGAG 3172 UUCCUGUUU 4311
X
CGAA AACAGGAA CCUAGCUG
9086 ACAGCUAG CUGAUGAG 3173 UCCUGUUUC 9312
X
CGAA AAACAGGA CUAGCUGU
4089 CACACAGC CUGAUGAG 3174 UGUUUCCUA 4313
X
CGAA AGGAAACA GCUGUGUG
4101 UGAGCAGG CUGAUGAG 3175 GUGUGAAUA 4319
X
CGAA AUUCACAC CCUGCUCA
4108 UUUGACGU CUGAUGAG 3176 UACCUGCUC 4315
X
2 O CGAA AGCAGGUA ACGUCAAA
4113 AUGCAUUU CUGAUGAG 3177 GCUCACGUC 4316
X
CGAA ACGUGAGC AAAUGCAU
4122 GAAACUUG CUGAUGAG 3178 AAAUGCAUA 4317
X
CGAA AUGCAUUU CAAGUUUC
2 5
q128 GAGAAUGA CUGAUGAG 3179 AUACAAGUU 4318
X
CGAA ACUUGUAU UCAUUCUC
4129 GGAGAAUG CUGAUGAG 3180 UACAAGUUU 4319
X
CGAA AACUUGUA CAUUCUCC
4130 GGGAGAAU CUGAUGAG 3181 ACAAGUUUC 4320
X
30
CGAA AAACUUGU AUUCUCCC
9133 AAAGGGAG CUGAUGAG 3182 AGUUUCAUU 4321
X
CGAA AUGAAACU CUCCCUUU
4134 GAAAGGGA CUGAUGAG 3183 GUUUCAUUC 4322
X
CGAA AAUGAAAC UCCCUUUC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
187
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
4136 GUGAAAGG CUGAUGAG 3189 UUCAUUCUC 4323
X
CGAA AGAAUGAA CCUUUCAC
4190 UUUAGUGA CUGAUGAG 3185 UUCUCCCUU 4324
X
CGAA AGGGAGAA UCACUAAA
9141 UUUUAGUG CUGAUGAG 3186 UCUCCCUUU 9325
X
CGAA AAGGGAGA CACUAAAA
4142 UUUUUAGU CUGAUGAG 3187 CUCCCUUUC 4326
X
CGAA AAAGGGAG ACUAAAAA
4146 UGUGUUUU CUGAUGAG 3188 CUUUCACUA 4327
X
CGAA AGUGAAAG AAAACACA
9170 UAGCAUUC CUGAUGAG 3189 AACAGACUU 4328
X
CGAA AGUCUGUU GAAUGCUA
4178 AGUAUAAC CUGAUGAG 3190 UGAAUGCUA 4329
X
CGAA AGCAUUCA GUUAUACU
9181 AUAAGUAU CUGAUGAG 3191 AUGCUAGUU 4330
X
CGAA ACUAGCAU AUACUUAU
4182 AAUAAGUA CUGAUGAG 3192 UGCUAGUUA 4331
X
CGAA AACUAGCA UACUUAUU
4189 CAAAUAAG CUGAUGAG 3193 CUAGUUAUA 9332
X
CGAA AUAACUAG CUUAUUUG
4187 AUACAAAU CUGAUGAG 3194 GUUAUACUU 4333
X
CGAA AGUAUAAC AUUUGUAU
2 5
4188 UAUACAAA CUGAUGAG 3195 UUAUACUUA 4334
X
CGAA AAGUAUAA UUUGUAUA
4190 CAUAUACA CUGAUGAG 3196 AUACUUAUU 4335
X
CGAA AUAAGUAU UGUAUAUG
4191 CCAUAUAC CUGAUGAG 3197 UACUUAUUU 4336
X
CGAA AAUAAGUA GUAUAUGG
9194 AUACCAUA CUGAUGAG 3198 UUAUUUGUA 4337
X
CGAA ACAAAUAA UAUGGUAU
4196 AAAUACCA CUGAUGAG 3199 AUUUGUAUA 4338
X
CGAA AUACAAAU UGGUAUUU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
188
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
4201 AAAAUAAA CUGAUGAG 3200 UAUAUGGUA 4339
X
CGAA ACCAUAUA UUUAUUUU
4203 AAAAAAUA CUGAUGAG 3201 UAUGGUAUU 4340
X
CGAA AUACCAUA UAUUUUUU
4204 GAAAAAAU CUGAUGAG 3202 AUGGUAUUU 9341
X
CGAA AAUACCAU AUUUUUUC
4205 AGAAAAAA CUGAUGAG 3203 UGGUAUUUA 9342
X
CGAA AAAUACCA UUUUUUCU
4207 AAAGAAAA CUGAUGAG 3204 GUAUUUAUU 4343
X
CGAA AUAAAUAC UUUUCUUU
4208 AAAAGAAA CUGAUGAG 3205 UAUUUAUUU 4344
X
CGAA AAUAAAUA UUUCUUUU
4209 GAAAAGAA CUGAUGAG 3206 AUUUAUUUU 4345
X
CGAA AAAUAAAU UUCUUUUC
4210 AGAAAAGA CUGAUGAG 3207 UUUAUUUUU 4346
X
CGAA AAAAUAAA UCUUUUCU
4211 AAGAAAAG CUGAUGAG 3208 UUAUUUUUU 4397
X
2 O CGAA AAAAAUAA CUUUUCUU
4212 AAAGAAAA CUGAUGAG 3209 UAUUUUUUC 9348
X
CGAA AAAAAAUA UUUUCUUU
4219 GUAAAGAA CUGAUGAG 3210 UUUUUUCUU 4349
X
CGAA AGAAAAAA UUCUUUAC
2 5
9215 UGUAAAGA CUGAUGAG 3211 UUUUUCUUU 4350
X
CGAA AAGAAAAA UCUUUACA
9216 UUGUAAAG CUGAUGAG 3212 UUUUCUUUU 4351
X
CGAA AAAGAAAA CUUUACAA
9217 UUUGUAAA CUGAUGAG 3213 UUUCUUUUC 9352
X
30
CGAA AAAAGAAA UUUACAAA
4219 GGUUUGUA CUGAUGAG 3219 UCUUUUCUU 9353
X
CGAA AGAAAAGA UACAAACC
4220 UGGUUUGU CUGAUGAG 3215 CUUUUCUUU 9354
X
CGAA AAGAAAAG ACAAACCA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
189
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
9221 AUGGUUUG CUGAUGAG 3216 UUUUCUUUA 4355
X
CGAA AAAGAAAA CAAACCAU
4230 AAUAACAA CUGAUGAG 3217 CAAACCAUU 4356
X
CGAA AUGGUUUG UUGUUAUU
9231 CAAUAACA CUGAUGAG 3218 AAACCAUUU 9357
X
CGAA AAUGGUUU UGUUAUUG
4232 UCAAUAAC CUGAUGAG 3219 AACCAUUUU 4358
X
CGAA AAAUGGUU GUUAUUGA
4235 UAGUCAAU CUGAUGAG 3220 CAUUUUGUU 4359
X
CGAA ACAAAAUG AUUGACUA
4236 UUAGUCAA CUGAUGAG 3221 AUUUUGUUA 4360
X
CGAA AACAAAAU UUGACUAA
4238 UGUUAGUC CUGAUGAG 3222 UUUGUUAUU 4361
X
CGAA AUAACAAA GACUAACA
4243 UGGCCUGU CUGAUGAG 3223 UAUUGACUA 4362
X
CGAA AGUCAAUA ACAGGCCA
4258 AAACUGGA CUGAUGAG 3224 CAAAGAGUC 4363
X
CGAA ACUCUUUG UCCAGUUU
4260 GUAAACUG CUGAUGAG 3225 AAGAGUCUC 4364
X
CGAA AGACUCUU CAGUUUAC
4265 GAAGGGUA CUGAUGAG 3226 UCUCCAGUU 4365
X
CGAA ACUGGAGA UACCCUUC
4266 UGAAGGGU CUGAUGAG 3227 CUCCAGUUU 9366
X
CGAA AACUGGAG ACCCUUCA
4267 CUGAAGGG CUGAUGAG 3228 UCCAGUUUA 4367
X
CGAA AAACUGGA CCCUUCAG
4272 CCAACCUG CUGAUGAG 3229 UUUACCCUU 4368
X
CGAA AGGGUAAA CAGGUUGG
4273 ACCAACCU CUGAUGAG 3230 UUACCCUUC 4369
X
CGAA AAGGGUAA AGGUUGGU
9278 AUUAAACC CUGAUGAG 3231 CUUCAGGUU 9370
X
CGAA ACCUGAAG GGUUUAAU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
190
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
4282 AUUGAUUA CUGAUGAG 3232 AGGUUGGUU 4371
X
CGAA ACCAACCU UAAUCAAU
4283 GAUUGAUU CUGAUGAG 3233 GGUUGGUUU 4372
X
CGAA AACCAACC AAUCAAUC
9284 UGAUUGAU CUGAUGAG 3234 GUUGGUUUA 4373
X
CGAA AAACCAAC AUCAAUCA
4287 UUCUGAUU CUGAUGAG 3235 GGUUUAAUC 4374
X
CGAA AUUAAACC AAUCAGAA
4291 CUAAUUCU CUGAUGAG 3236 UAAUCAAUC 4375
X
CGAA AUUGAUUA AGAAUUAG
4297 CUAAUUCU CUGAUGAG 3237 AUCAGAAUU 4376
X
CGAA AUUCUGAU AGAAUUAG
4298 UCUAAUUC CUGAUGAG 3238 UCAGAAUUA 4377
X
CGAA AAUUCUGA GAAUUAGA
4303 CAUGCUCU CUGAUGAG 3239 AUUAGAAUU 4378
X
CGAA AUUCUAAU AGAGCAUG
4309 CCAUGCUC CUGAUGAG 3240 UUAGAAUUA 9379
X
2 O CGAA AAUUCUAA GAGCAUGG
4319 AUAGUGAU GUGAUGAG 3291 GGGAGGGUC 4380
X
CGAA ACCCUCCC AUCACUAU
9322 GUCAUAGU CUGAUGAG 3242 AGGGUCAUC 4381
X
CGAA AUGACCCU ACUAUGAC
4326 UUAGGUCA CUGAUGAG 3243 UCAUCACUA 4382
X
CGAA AGUGAUGA UGACCUAA
4333 AAAUAAUU CUGAUGAG 3294 UAUGACCUA 4383
X
CGAA AGGUCAUA AAUUAUUU
9337 CAGUAAAU CUGAUGAG 3245 ACCUAAAUU 4384
X
CGAA AUUUAGGU AUUUACUG
4338 GCAGUAAA CUGAUGAG 3246 CCUAAAUUA 4385
X
CGAA AAUUUAGG UUUACUGC
4340 UUGCAGUA CUGAUGAG 3247 UAAAUUAUU 4386
X
CGAA AUAAUUUA UACUGCAA
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
191
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
4391 UUUGCAGU CUGAUGAG 3298 AAAUUAUUU 4387
X
CGAA AAUAAUUU ACUGCAAA
4342 UUUUGCAG CUGAUGAG 3249 AAUUAUUUA 9388
X
CGAA AAAUAAUU CUGCAAAA
4358 UUUAUAAA CUGAUGAG 3250 AAGAAAAUC 4389
X
CGAA AUUUUCUU UUUAUAAA
4360 CAUUUAUA CUGAUGAG 3251 GAAAAUCUU 4390
X
CGAA AGAUUUUC UAUAAAUG
4361 ACAUUUAU CUGAUGAG 3252 AAAAUCUUU 4391
X
CGAA AAGAUUUU AUAAAUGU
4362 UACAUUUA CUGAUGAG 3253 AAAUCUUUA 9392
X
CGAA AAAGAUUU UAAAUGUA
9364 GGUACAUU CUGAUGAG 3259 AUCUUUAUA 4393
X
CGAA AUAAAGAU AAUGUACC
4370 CUCUCUGG CUGAUGAG 3255 AUAAAUGUA 4399
X
CGAA ACAUUUAU CCAGAGAG
4382 AUUAAAAC CUGAUGAG 3256 GAGAGAGUU 4395
X
2 O CGAA ACUCUCUC GUUUUAAU
4385 GUUAUUAA CUGAUGAG 3257 AGAGUUGUU 4396
X
CGAA ACAACUCU UUAAUAAC
4386 AGUUAUUA CUGAUGAG 3258 GAGUUGUUU 4397
X
CGAA AACAACUC UAAUAACU
2 5
4387 AAGUUAUU CUGAUGAG 3259 AGUUGUUUU 4398
X
CGAA AAACAACU AAUAACUU
4388 UAAGUUAU CUGAUGAG 3260 GUUGUUUUA 4399
X
CGAA AAAACAAC AUAACUUA
4391 AGAUAAGU CUGAUGAG 3261 GUUUUAAUA 4400
X
30
CGAA AUUAAAAC ACUUAUCU
4395 UUAUAGAU CUGAUGAG 3262 UAAUAACUU 4401
X
CGAA AGUUAUUA AUCUAUAA
4396 UUUAUAGA CUGAUGAG 3263 AAUAACUUA 4402
X
CGAA AAGUUAUU UCUAUAAA
CA 02324421 2000-09-26
WO 99/50403 PGTNS99/06507
192
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
4398 AGUUUAUA CUGAUGAG 3264 UAACUUAUC 4403
X
CGAA AUAAGUUA UAUAAACU
4400 AUAGUUUA CUGAUGAG 3265 ACUUAUCUA 4909
X
CGAA AGAUAAGU UAAACUAU
4402 UUAUAGUU CUGAUGAG 3266 UUAUCUAUA 9405
X
CGAA AUAGAUAA AACUAUAA
4907 AGAGGUUA CUGAUGAG 3267 UAUAAACUA 4406
X
CGAA AGUUUAUA UAACCUCU
4409 GGAGAGGU CUGAUGAG 3268 UAAACUAUA 9407
X
CGAA AUAGUUUA ACCUCUCC
4414 AUGAAGGA CUGAUGAG 3269 UAUAACCUC 4908
X
CGAA AGGUUAUA UCCUUCAU
4416 UCAUGAAG CUGAUGAG 3270 UAACCUCUC 4409
X
CGAA AGAGGUUA CUUCAUGA
4419 CUGUCAUG CUGAUGAG 3271 CCUCUCCUU 4910
X
CGAA AGGAGAGG CAUGACAG
4920 GCUGUCAU CUGAUGAG 3272 CUCUCCUUC 4411
X
CGAA AAGGAGAG AUGACAGC
4431 GUGGGGUG CUGAUGAG 3273 GACAGCCUC 4412
X
CGAA AGGCUGUC CACCCCAC
4952 AUUUCUUA CUGAUGAG 3279 CAAAAGGUU 4413
X
CGAA ACCUUUUG UAAGAAAU
4453 UAUUUCUU CUGAUGAG 3275 AAAAGGUUU 4414
X
CGAA AACCUUUU AAGAAAUA
4954 CUAUUUCU CUGAUGAG 3276 AAAGGUUUA 4415
X
CGAA AAACCUUU AGAAAUAG
4461 UAUAAUUC CUGAUGAG 3277 UAAGAAAUA 4916
X
CGAA AUUUCUUA GAAUUAUA
9466 ACAGUUAU CUGAUGAG 3278 AAUAGAAUU 4417
X
CGAA AUUCUAUU AUAACUGU
4467 UACAGUUA CUGAUGAG 3279 AUAGAAUUA 4418
X
CGAA AAUUCUAU UAACUGUA
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
193
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
4969 UUUACAGU CUGAUGAG 3280 AGAAUUAUA 4919
X
CGAA AUAAUUCU ACUGUAAA
4475 AACAUCUU CUGAUGAG 3281 AUAACUGUA 4920
X
CGAA ACAGUUAU AAGAUGUU
4483 CUGAAAUA CUGAUGAG 3282 AAAGAUGUU 4421
X
CGAA ACAUCUUU UAUUUCAG
4489 CCUGAAAU CUGAUGAG 3283 AAGAUGUUU 4422
X
CGAA AACAUCUU AUUUCAGG
9485 GCCUGAAA CUGAUGAG 3289 AGAUGUUUA 4423
X
CGAA AAACAUCU UUUCAGGC
4487 AUGCCUGA CUGAUGAG 3285 AUGUUUAUU 4424
X
CGAA AUAAACAU UCAGGCAU
4488 AAUGCCUG CUGAUGAG 3286 UGUUUAUUU 4425
X
CGAA AAUAAACA CAGGCAUU
4489 CAAUGCCU CUGAUGAG 3287 GUUUAUUUC 4426
X
CGAA AAAUAAAC AGGCAUUG
4496 AAAUAUCC CUGAUGAG 3288 UCAGGCAUU 4427
X
CGAA AUGCCUGA GGAUAUUU
9501 GUAAAAAA CUGAUGAG 3289 CAUUGGAUA 4428
X
CGAA AUCCAAUG UUUUUUAC
9503 AAGUAAAA CUGAUGAG 3290 UUGGAUAUU 4429
X
CGAA AUAUCCAA UUUUACUU
2 5 4509 AAAGUAAA CUGAUGAG 3291 UGGAUAUUU 4930
X
CGAA AAUAUCCA UUUACUUU
4505 UAAAGUAA CUGAUGAG 3292 GGAUAUUUU 4931
X
CGAA AAAUAUCC UUACUUUA
9506 CUAAAGUA CUGAUGAG 3293 GAUAUUUUU 4432
X
CGAA AAAAUAUC UACUUUAG
4507 UCUAAAGU CUGAUGAG 3294 AUAUUUUUU 4433
X
' CGAA AAAAAUAU ACUUUAGA
4508 UUCUAAAG CUGAUGAG 3295 UAUUUUUUA 4434
X
CGAA AAAAAAUA CUUUAGAA
CA 02324421 2000-09-26
WO 99!50403 PCT/US99/06507
194
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
4511 GGCUUCUA CUGAUGAG 3296 UUUUUACUU 4435
X
CGAA AGUAAAAA UAGAAGCC
4512 AGGCUUCU CUGAUGAG 3297 UUUUACUUU 4936
X
CGAA AAGUAAAA AGAAGCCU
4513 CAGGCUUC CUGAUGAG 3298 UUUACUUUA 4437
X
CGAA AAAGUAAA GAAGCCUG
4525 AGAAACAU CUGAUGAG 3299 GCCUGCAUA 4438
X
CGAA AUGCAGGC AUGUUUCU
4530 AAUCCAGA CUGAUGAG 3300 CAUAAUGUU 4439
X
CGAA ACAUUAUG UCUGGAUU
4531 AAAUCCAG CUGAUGAG 3301 AUAAUGUUU 9440
X
CGAA AACAUUAU CUGGAUUU
9532 UAAAUCCA CUGAUGAG 3302 UAAUGUUUC 4441
X
CGAA AAACAUUA UGGAUUUA
9538 AGUAUGUA CUGAUGAG 3303 UUCUGGAUU 4492
X
CGAA AUCCAGAA UACAUACU
4539 CAGUAUGU CUGAUGAG 3304 UCUGGAUUU 9443
X
CGAA AAUCCAGA ACAUACUG
4590 ACAGUAUG CUGAUGAG 3305 CUGGAUUUA 4949
X
CGAA AAAUCCAG CAUACUGU
4544 UGUUACAG CUGAUGAG 3306 AUUUACAUA 4445
X
CGAA AUGUAAAU CUGUAACA
45qg CUGAAUGU CUGAUGAG 3307 CAUACUGUA 9446
X
CGAA ACAGUAUG ACAUUCAG
4554 AAUUCCUG CUGAUGAG 3308 UGUAACAUU 4447
X
CGAA AUGUUACA CAGGAAUU
4555 GAAUUCCU CUGAUGAG 3309 GUAACAUUC 4498
X
CGAA AAUGUUAC AGGAAUUC
4562 UCUCCAAG CUGAUGAG 3310 UCAGGAAUU 4499
X
CGAA AUUCCUGA CUUGGAGA
9563 UUCUCCAA CUGAUGAG 3311 CAGGAAUUC 4950
X
CGAA AAUUCCUG UUGGAGAA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
195
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
4565 UCUUCUCC CUGAUGAG 3312 GGAAUUCUU 4451
X
CGAA AGAAUUCC GGAGAAGA
4579 AGUGAAUA CUGAUGAG 3313 AGAUGGGUU 4452
X
CGAA ACCCAUCU UAUUCACU
4580 CAGUGAAU CUGAUGAG 3314 GAUGGGUUU 4453
X
CGAA AACCCAUC AUUCACUG
4581 UCAGUGAA CUGAUGAG 3315 AUGGGUUUA 4454
X
CGAA AAACCCAU UUCACUGA
4583 GUUCAGUG CUGAUGAG 3316 GGGUUUAUU 4455
X
CGAA AUAAACCC CACUGAAG
4584 AGUUCAGU CUGAUGAG 3317 GGUUUAUUC 4956
X
CGAA AAUAAACC ACUGAACU
4593 CCGCACUA CUGAUGAG 3318 ACUGAACUC 4457
X
CGAA AGUUCAGU UAGUGCGG
4595 AACCGCAC CUGAUGAG 3319 UGAACUCUA 4458
X
CGAA AGAGUUCA GUGCGGUU
4603 AGUGAGUA CUGAUGAG 3320 AGUGCGGUU 4459
X
2 a CGAA ACCGCACU UACUCACU
4604 CAGUGAGU CUGAUGAG 3321 GUGCGGUUU 4960
X
CGAA AACCGCAC ACUCACUG
4605 GCAGUGAG CUGAUGAG 3322 UGCGGUUUA 4461
X
CGAA AAACCGCA GUCACUGC
2 5
4608 GCAGCAGU CUGAUGAG 3323 GGUUUACUC 4462
X
CGAA AGUAAACC ACUGCUGC
4621 AUAUACAG CUGAUGAG 3329 CUGCAAAUA 4963
X
CGAA AUUUGCAG CUGUAUAU
4626 CCUGAAUA CUGAUGAG 3325 AAUACUGUA 4964
X
30
CGAA ACAGUAUU UAUUCAGG
4628 GUCCUGAA CUGAUGAG 3326 UACUGUAUA 4465
X
CGAA AUACAGUA UUCAGGAC
4630 AAGUCCUG CUGAUGAG 3327 CUGUAUAUU 4466
X
CGAA AUAUACAG CAGGACUU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
196
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
4631 CAAGUCCU CUGAUGAG 3328 UGUAUAUUC 9967
X
CGAA AAUAUACA AGGACUUG
4638 UUUCUUUC CUGAUGAG 3329 UCAGGACUU 4468
X
CGAA AGUCCUGA GAAAGAAA
4659 UAGUUCCA CUGAUGAG 3330 GAAUGCCUA 4469
X
CGAA AGGCAUUC UGGAACUA
4667 GGAUCCAC CUGAUGAG 3331 AUGGAACUA 4970
X
CGAA AGUUCCAU GUGGAUCC
9679 UCAGUUUG CUGAUGAG 3332 UAGUGGAUC 4471
X
CGAA AUCCACUA CAAACUGA
9684 UUAUACUG CUGAUGAG 3333 AAACUGAUC 4472
X
CGAA AUCAGUUU CAGUAUAA
4689 UAGUCUUA CUGAUGAG 3339 GAUCCAGUA 4473
X
CGAA ACUGGAUC UAAGACUA
4691 AGUAGUCU CUGAUGAG 3335 UCCAGUAUA 4474
X
CGAA AUACUGGA AGACUACU
4697 AGAUUCAG CUGAUGAG 3336 AUAAGACUA 4475
X
CGAA AGUCUUAU CUGAAUCU
4704 UGGUAGCA CUGAUGAG 3337 UACUGAAUC 4976
X
CGAA AUUCAGUA UGCUACCA
4709 UGUUUUGG CUGAUGAG 3338 AAUCUGCUA 4477
X
CGAA AGCAGAUU CCAAAACA
4720 CACUGAUU CUGAUGAG 3339 AAAACAGUU 4478
X
CGAA ACUGUUUU AAUCAGUG
9721 UCACUGAU CUGAUGAG 3390 AAACAGUUA 4479
X
CGAA AACUGUUU AUCAGUGA
4724 GACUCACU CUGAUGAG 3341 CAGUUAAUC 4480
X
CGAA AUUAACUG AGUGAGUC
4732 GAACACUC CUGAUGAG 3342 CAGUGAGUC 4481
X
CGAA ACUCACUG GAGUGUUC
4739 AAAAAUAG CUGAUGAG 3343 UCGAGUGUU 9482
X
CGAA ACACUCGA CUAUUUUU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
197
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
9740 AAAAAAUA CUGAUGAG 3394 CGAGUGUUC 4483
X
CGAA AACACUCG UAUUUUUU
4742 ACAAAAAA CUGAUGAG 3395 AGUGUUCUA 4484
X
CGAA AGAACACU UUUUUUGU
4799 AAACAAAA CUGAUGAG 3346 UGUUCUAUU 49$5
X
CGAA AUAGAACA UUUUGUUU
9745 AAAACAAA CUGAUGAG 3347 GUUCUAUUU 4486
X
CGAA AAUAGAAC UUUGUUUU
4746 CAAAACAA CUGAUGAG 3348 UUCUAUUUU 4487
X
CGAA AAAUAGAA UUGUUUUG
4797 ACAAAACA CUGAUGAG 3399 UCUAUUUUU 498$
X
CGAA AAAAUAGA UGUUUUGU
9748 AACAAAAC CUGAUGAG 3350 CUAUUUUUU 4489
X
CGAA AAAAAUAG GUUUUGUU
4751 GGAAACAA CUGAUGAG 3351 UUUUUUGUU 4490
X
CGAA ACAAAAAA UUGUUUCC
4752 AGGAAACA CUGAUGAG 3352 UUUUUGUUU 4491
X
2 O CGAA AACAAAAA UGUUUCCU
9753 GAGGAAAC CUGAUGAG 3353 UUUUGUUUU 4492
X
CGAA AAACAAAA GUUUCCUC
4756 GGGGAGGA CUGAUGAG 3354 UGUUUUGUU 4493
X
CGAA ACAAAACA UCCUCCCC
4757 AGGGGAGG CUGAUGAG 3355 GUUUUGUUU 4494
X
CGAA AACAAAAC CCUCCCCU
4758 UAGGGGAG CUGAUGAG 3356 UUUUGUUUC 4495
X
CGAA AAACAAAA CUCCCCUA
4761 AGAUAGGG CUGAUGAG 3357 UGUUUCCUC 9496
X
CGAA AGGAAACA CCCUAUCU
4766 AAUACAGA CUGAUGAG 3358 CCUCCCCUA 4497
X
CGAA AGGGGAGG UCUGUAUU
4768 GGAAUACA CUGAUGAG 3359 UCCCCUAUC 4998
X
CGAA AUAGGGGA UGUAUUCC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
198
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
4772 UUUGGGAA CUGAUGAG 3360 CUAUCUGUA 4499
X
CGAA ACAGAUAG UUCCCAAA
4774 UUUUUGGG CUGAUGAG 3361 AUCUGUAUU 4500
X
CGAA AUACAGAU CCCAAAAA
9775 AUUUUUGG CUGAUGAG 3362 UCUGUAUUC 9501
X
CGAA AAUACAGA CCAAAAAU
9789 CCCAAAGU CUGAUGAG 3363 CCAAAAAUU 9502
X
CGAA AUUUUUGG ACUUUGGG
4785 CCCCAAAG CUGAUGAG 3364 CAAAAAUUA 4503
X
CGAA AAUUUUUG CUUUGGGG
4788 UAGCCCCA CUGAUGAG 3365 AAAUUACUU 4504
X
CGAA AGUAAUUU UGGGGCUA
4789 UUAGCCCC CUGAUGAG 3366 AAUUACUUU 4505
X
CGAA AAGUAAUU GGGGCUAA
4796 UGUUAAAU CUGAUGAG 3367 UUGGGGCUA 4506
X
CGAA AGCCCCAA AUUUAACA
4799 UCUUGUUA CUGAUGAG 3368 GGGCUAAUU 4507
X
2~ CGAA AUUAGCCC UAACAAGA
4800 UUCUUGUU CUGAUGAG 3369 GGCUAAUUU 9508
X
CGAA AAUUAGCC AACAAGAA
4801 GUUCUUGU CUGAUGAG 3370 GCUAAUUUA 4509
X
CGAA AAAUUAGC ACAAGAAC
4811 ACAAUUUA CUGAUGAG 3371 CAAGAACUU 4510
X
CGAA AGUUCUUG UAAAUUGU
9812 CACAAUUU CUGAUGAG 3372 AAGAACUUU 4511
X
CGAA AAGUUCUU AAAUUGUG
4813 ACACAAUU CUGAUGAG 3373 AGAACUUUA 4512
X
CGAA AAAGUUCU AAUUGUGU
4817 UAAAACAC CUGAUGAG 3374 CUUUAAAUU 4513
X
CGAA AUUUAAAG GUGUUUUA
9822 ACAAUUAA CUGAUGAG 3375 AAUUGUGUU 9514
X
CGAA ACACAAUU UUAAUUGU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
199
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
9823 UACAAUUA CUGAUGAG 3376 AUUGUGUUU 4515
X
CGAA AACACAAU UAAUUGUA
4824 UUACAAUU CUGAUGAG 3377 UUGUGUUUU 9516
X
CGAA AAACACAA AAUUGUAA
4825 UUUACAAU CUGAUGAG 3378 UGUGUUUUA 451?
X
CGAA AAAACACA AUUGUAAA
4828 AUUUUUAC CUGAUGAG 3379 GUUUUAAUU 4518
X
CGAA AUUAAAAC GUAAAAAU
4831 GCCAUUUU CUGAUGAG 3380 UUAAUUGUA 9519
X
CGAA ACAAUUAA AAAAUGGC
9852 AGAGUAAU CUGAUGAG 3381 GGUGGAAUU 4520
X
CGAA AUUCCACC AUUACUCU
I5 4853 UAGAGUAA CUGAUGAG 3382 GUGGAAUUA 9521
X
CGAA AAUUCCAC UUACUCUA
9855 UAUAGAGU CUGAUGAG 3383 GGAAUUAUU 4522
X
CGAA AUAAUUCC ACUCUAUA
4856 GUAUAGAG CUGAUGAG 3389 GAAUUAUUA 4523
X
CGAA AAUAAUUC CUCUAUAC
9859 AAUGUAUA CUGAUGAG 3385 UUAUUACUC 9529
X
CGAA AGUAAUAA UAUACAUU
9861 UGAAUGUA CUGAUGAG 3386 AUUACUCUA 4525
X
CGAA AGAGUAAU UACAUUCA
25
4863 GUUGAAUG CUGAUGAG 3387 UACUCUAUA 452 6
X
CGAA AUAGAGUA CAUUCAAC
4867 CUCUGUUG CUGAUGAG 3388 CUAUACAUU 4527
X
CGAA AUGUAUAG CAACAGAG
9868 UCUCUGUU CUGAUGAG 3389 UAUACAUUC 4528
X
30
CGAA AAUGUAUA AACAGAGA
4883 UUCAUAUC CUGAUGAG 3390 GACUGAAUA 4529
X
CGAA AUUCAGUC GAUAUGAA
4887 AGCUUUCA CUGAUGAG 3391 GAAUAGAUA 4530
X
CGAA AUCUAUUC UGAAAGCU
CA 02324421 2000-09-26
WO 99/50403 PCTNS99/06507
200
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
4899 UUAAAAAA CUGAUGAG 3392 AAGCUGAUU 4531
X
CGAA AUCAGCUU UUUUUUAA
4900 AUUAAAAA CUGAUGAG 3393 AGCUGAUUU 4532
X
CGAA AAUCAGCU UUUUUAAU
4901 AAUUAAAA CUGAUGAG 3394 GCUGAUUUU 4533
X
CGAA AAAUCAGC UUUUAAUU
9902 UAAUUAAA CUGAUGAG 3395 CUGAUUUUU 4534
X
CGAA AAAAUCAG UUUAAUUA
4903 GUAAUUAA CUGAUGAG 3396 UGAUUUUUU 4535
X
CGAA AAAAAUCA UUAAUUAC
4904 GGUAAUUA CUGAUGAG 3397 GAUUUUUUU 4536
X
CGAA AAAAAAUC UAAUUACC
4905 UGGUAAUU CUGAUGAG 3398 AUUUUUUUU 4537
X
CGAA AAAAAAAU AAUUACCA
4906 AUGGUAAU CUGAUGAG 3399 UUUUUUUUA 4538
X
CGAA APIA AUUACCAU
9909 AGCAUGGU CUGAUGAG 3400 UUUUUAAUU 4539
X
2 O CGAA AUUAAAAA ACCAUGCU
4910 AAGCAUGG CUGAUGAG 3401 UUUUAAUUA 4540
X
CGAA AAUUAAAA CCAUGCUU
9918 ACAUUGUG CUGAUGAG 3402 ACCAUGCUU 4591
X
CGAA AGCAUGGU CACAAUGU
2 5
4919 AACAUUGU CUGAUGAG 3403 CCAUGCUUC 4542
X
CGAA AAGCAUGG ACAAUGUU
4927 UAUAACUU CUGAUGAG 3904 CACAAUGUU 4593
X
CGAA ACAUUGUG AAGUUAUA
4928 AUAUAACU CUGAUGAG 3405 ACAAUGUUA 4594
X
30
CGAA AACAUUGU AGUUAUAU
9932 CCCCAUAU CUGAUGAG 3406 UGUUAAGUU 4545
X
CGAA ACUUAACA AUAUGGGG
4933 UCCCCAUA CUGAUGAG 3907 GUUAAGUUA 4546
X
CGAA AACUUAAC UAUGGGGA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
201
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
4935 GCUCCCCA CUGAUGAG 3908 UAAGUUAUA 4547
X
CGAA AUAACUUA UGGGGAGC
9961 AAACAAAU CUGAUGAG 3409 CAGGUGCUA 4548
X
CGAA AGCACCUG AUUUGUUU
9964 CCAAAACA CUGAUGAG 3410 GUGCUAAUU 4549
X
CGAA AUUAGCAC UGUUUUGG
4965 UCCAAAAC CUGAUGAG 3411 UGCUAAUUU 4550
X
CGAA AAUUAGCA GUUUUGGA
9968 AUAUCCAA CUGAUGAG 3912 UAAUUUGUU 4551
X
CGAA ACAAAUUA UUGGAUAU
4969 UAUAUCCA CUGAUGAG 3413 AAUUUGUUU 9552
X
CGAA AACAAAUU UGGAUAUA
9970 CUAUAUCC CUGAUGAG 3914 AUUUGUUUU 4553
X
CGAA AAACAAAU GGAUAUAG
4975 UUAUACUA CUGAUGAG 3415 UUUUGGAUA 9554
X
CGAA AUCCAAAA UAGUAUAA
9977 GCUUAUAC CUGAUGAG 3416 UUGGAUAUA 4555
X
CGAA AUAUCCAA GUAUAAGC
4980 ACUGCUUA CUGAUGAG 3417 GAUAUAGUA 9556
X
CGAA ACUAUAUC UAAGCAGU
4982 ACACUGCU CUGAUGAG 3418 UAUAGUAUA 9557
X
CGAA AUACUAUA AGCAGUGU
q.ggl AAAACACA CUGAUGAG 3419 AGCAGUGUC 4558
X
CGAA ACACUGCU UGUGUUUU
9997 UCUUUCAA CUGAUGAG 3920 GUCUGUGUU 4559
X
CGAA ACACAGAC UUGAAAGA
9998 UUCUUUCA CUGAUGAG 3921 UCUGUGUUU 9560
X
CGAA AACACAGA UGAAAGAA
4999 AUUCUUUC CUGAUGAG 3422 CUGUGUUUU 4561
X
CGAA AAACACAG GAAAGAAU
5008 CUGUGUUC CUGAUGAG 3423 GAAAGAAUA 4562
X
CGAA AUUCUUUC GAACACAG
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
202
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
5018 GCACUACA CUGAUGAG 3429 AACACAGUU 4563
X
CGAA ACUGUGUU UGUAGUGC
5019 GGCACUAC CUGAUGAG 3425 ACACAGUUU 4564
X
CGAA AACUGUGU GUAGUGCC
5022 AGUGGCAC CUGAUGAG 3426 CAGUUUGUA 9565
X
CGAA ACAAACUG GUGCCACU
5033 CCCAAAAC CUGAUGAG 3427 GCCACUGUU 9566
X
CGAA ACAGUGGC GUUUUGGG
5036 CCCCCCAA CUGAUGAG 3428 ACUGUUGUU 4567
X
CGAA ACAACAGU UUGGGGGG
5037 CCCCCCCA CUGAUGAG 3429 CUGUUGUUU 4568
X
CGAA AACAACAG UGGGGGGG
5038 CCCCCCCC CUGAUGAG 3430 UGUUGUUUU 4569
X
CGAA AAACAACA GGGGGGGG
5049 AAGAAAAA CUGAUGAG 3931 GGGGGGCUU 9570
X
CGAA AGCCCCCC UUUUUCUU
5050 AAAGAAAA CUGAUGAG 3932 GGGGGCUUU 4571
X
CGAA AAGCCCCC UUUUCUUU
5051 AAAAGAAA CUGAUGAG 3433 GGGGCUUUU 4572
X
CGAA AAAGCCCC UUUCUUUU
5052 AAAAAGAA CUGAUGAG 3434 GGGCUUUUU 4573
X
CGAA AAAAGCCC UUCUUUUU
2 5
5053 GAAAAAGA CUGAUGAG 3435 GGCUUUUUU 4574
X
CGAA AAAAAGCC UCUUUUUC
5054 GGAAAAAG CUGAUGAG 3436 GCUUUUUUU 9575
X
CGAA AAAAAAGC CUUUUUGC
5055 CGGAAAAA CUGAUGAG 3437 CUUUUUUUC 4576
X
CGAA AAAAAAAG UUUUUCCG
505? UCCGGAAA CUGAUGAG 3438 UUUUUUCUU 4577
X
CGAA AGAAAAAA UUUCCGGA
5058 UUCCGGAA CUGAUGAG 3939 UUUUUCUUU 4578
X
CGAA AAGAAAAA UUCCGGAA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
203
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
5059 UUUCCGGA CUGAUGAG 3490 UUUUCUUUU 4579
X
CGAA AAAGAAAA UCCGGAAA
5060 UUUUCCGG CUGAUGAG 3441 UUUCUUUUU 4580
X
CGAA AAAAGAAA CCGGAAAA
5061 AUUUUCCG CUGAUGAG 3442 UUCUUUUUC 4581
X
GGAA AAAAAGAA CGGAAAAU
5070 GGUUUAAG CUGAUGAG 3443 CGGAAAAUC 9582
X
CGAA AUUUUCCG CUUAAACC
5073 UAAGGUUU CUGAUGAG 3994 AAAAUCCUU 4583
X
CGAA AGGAUUUU AAACCUUA
5079 UUAAGGUU CUGAUGAG 3445 AAAUCCUUA 9584
X
CGAA AAGGAUUU AACCUUAA
5080 AGUAUCUU CUGAUGAG 3946 UUAAACCUU 4585
X
CGAA AGGUUUAA AAGAUACU
5081 UAGUAUCU CUGAUGAG 3447 UAAACCUUA 4586
X
CGAA AAGGUUUA AGAUACUA
5086 GUCCUUAG CUGAUGAG 3448 CUUAAGAUA 9587
X
2 O CGAA AUCUUAAG CUAAGGAC
5089 AACGUCCU CUGAUGAG 3949 AAGAUACUA 9588
X
CGAA AGUAUCUU AGGACGUU
5097 ACCAAAAC CUGAUGAG 3450 AAGGACGUU 4589
X
CGAA ACGUCCUU GUUUUGGU
5100 ACAACCAA CUGAUGAG 3451 GACGUUGUU 4590
X
CGAA ACAACGUC UUGGUUGU
5101 UACAACCA CUGAUGAG 3452 ACGUUGUUU 4591
X
CGAA AACAACGU UGGUUGUA
5102 GUACAACC CUGAUGAG 3453 CGUUGUUUU 9592
X
CGAA AAACAACG GGUUGUAC
5106 CCAAGUAC CUGAUGAG 3459 GUUUUGGUU 4593
X
CGAA ACCAAAAC GUACUUGG
5109 AUUCCAAG CUGAUGAG 3455 UUGGUUGUA 4599
X
CGAA ACAACCAA CUUGGAAU
CA 02324421 2000-09-26
WO 99/50403 PGT/US99/06507
204
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
5112 AGAAUUCC CUGAUGAG 3456 GUUGUACUU 4595
X
CGAA AGUACAAC GGAAUUCU
5118 UGACUAAG CUGAUGAG 3957 CUUGGAAUU 4596
X
CGAA AUUCCAAG CUUAGUCA
5119 GUGACUAA CUGAUGAG 3458 UUGGAAUUC 4597
X
CGAA AAUUCCAA UUAGUCAC
5121 UUGUGACU CUGAUGAG 3959 GGAAUUCUU 4598
X
CGAA AGAAUUCC AGUCACAA
5122 UUUGUGAC CUGAUGAG 3960 GAAUUCUUA 4599
X
CGAA AAGAAUUC GUCACAAA
5125 UAUUUUGU CUGAUGAG 3461 UUCUUAGUC 4600
X
CGAA ACUAAGAA ACAAAAUA
5133 ACAAAAUA CUGAUGAG 3962 CACAAAAUA 9601
X
CGAA AUUUUGUG UAUUUUGU
5135 AAACAAAA CUGAUGAG 3463 CAAAAUAUA 4602
X
CGAA AUAUUUUG UUUUGUUU
5137 GUAAACAA CUGAUGAG 3969 AAAUAUAUU 4603
X
2 d CGAA AUAUAUUU UUGUUUAC
5138 UGUAAACA CUGAUGAG 3465 AAUAUAUUU 4604
X
CGAA AAUAUAUU UGUUUACA
5139 UUGUAAAC CUGAUGAG 3466 AUAUAUUUU 4605
X
CGAA AAAUAUAU GUUUACAA
2 5
5142 UUUUUGUA CUGAUGAG 3467 UAUUUUGUU 4606
X
CGAA ACAAAAUA UACAAAAA
5143 AUUUUUGU CUGAUGAG 3968 AUUUUGUUU 4607
X
CGAA AACAAAAU ACAAAAAU
5144 AAUUUUUG CUGAUGAG 3469 UUUUGUUUA 9608
X
30
CGAA AAACAAAA CAAAAAUU
5152 UUUACAGA CUGAUGAG 3470 ACAAAAAUU 4609
X
CGAA AUUUUUGU UCUGUAAA
5153 UUUUACAG CUGAUGAG 3471 CAAAAAUUU 4610
X
CGAA AAUUUUUG CUGUAAAA
CA 02324421 2000-09-26
WO 99/50403 PGT/US99/06507
205
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
5159 GUUUUACA CUGAUGAG 3972 AAAAAUUUC 4611
X
CGAA AAAUUUUU UGUAAAAC
5158 ACCUGUUU CUGAUGAG 3473 AUUUCUGUA 9612
X
CGAA ACAGAAAU AAACAGGU
5167 ACUGUUAU CUGAUGAG 3474 AAACAGGUU 4613
X
CGAA ACCUGUUU AUAACAGU
5168 CACUGUUA CUGAUGAG 3475 AACAGGUUA 4614
X
CGAA AACCUGUU UAACAGUG
5170 AACACUGU CUGAUGAG 3476 CAGGUUAUA 4615
X
CGAA AUAACCUG ACAGUGUU
5178 AGACUUUA CUGAUGAG 347? AACAGUGUU 4616
X
CGAA ACACUGUU UAAAGUCU
5179 GAGACUUU CUGAUGAG 3978 ACAGUGUUU 4617
X
CGAA AACACUGU AAAGUCUC
5180 UGAGACUU CUGAUGAG 3479 CAGUGUUUA 4618
X
CGAA AAACACUG AAGUCUCA
5185 GAAACUGA CUGAUGAG 3480 UUUAAAGUC 4619
X
CGAA ACUUUAAA UCAGUUUC
5187 AAGAAACU CUGAUGAG 3481 UAAAGUCUC 9620
X
CGAA AGACUUUA AGUUUCUU
5191 AAGCAAGA CUGAUGAG 3982 GUCUCAGUU 4621
X
CGAA ACUGAGAC UCUUGCUU
5192 CAAGCAAG CUGAUGAG 3483 UCUCAGUUU 4622
X
CGAA AACUGAGA CUUGCUUG
5193 CCAAGCAA CUGAUGAG 3489 CUCAGUUUC 4623
X
CGAA AAACUGAG UUGCUUGG
5195 CCCCAAGC CUGAUGAG 3485 CAGUUUCUU 4624
X
CGAA AGAAACUG GCUUGGGG
5199 AGUUCCCC CUGAUGAG 3486 UUCUUGCUU 4625
X
CGAA AGCAAGAA GGGGAACU
5208 AGGGACAC CUGAUGAG 3487 GGGGAACUU 4626
X
CGAA AGUUCCCC GUGUCCCU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
206
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
5213 ACAUUAGG CUGAUGAG 3488 ACUUGUGUC 4627
X
CGAA ACACAAGU CCUAAUGU
5217 UAACACAU CUGAUGAG 3489 GUGUCCCUA 9628
X
CGAA AGGGACAC AUGUGUUA
5224 AGCAAUCU CUGAUGAG 3990 UAAUGUGUU 4629
X
CGAA ACACAUUA AGAUUGCU
5225 UAGCAAUC CUGAUGAG 3491 AAUGUGUUA 4630
X
CGAA AACACAUU GAUUGCUA
5229 AAUCUAGC CUGAUGAG 3992 UGUUAGAUU 4631
X
CGAA AUCUAACA GCUAGAUU
5233 UAGCAAUC CUGAUGAG 3993 AGAUUGCUA 4632
X
CGAA AGCAAUCU GAUUGCUA
5237 UCCUUAGC CUGAUGAG 3999 UGCUAGAUU 4633
X
CGAA AUCUAGCA GCUAAGGA
5241 CAGCUCCU CUGAUGAG 3495 AGAUUGCUA 4634
X
CGAA AGCAAUCU AGGAGGUG
5252 CUGUCAAG CUGAUGAG 3496 GAGCUGAUA 4635
X
2 O CGAA AUCAGCUC CUUGACAG
5255 AAACUGUC CUGAUGAG 3497 CUGAUACUU 4636
X
CGAA AGUAUCAG GACAGUUU
5262 GUCUAAAA CUGAUGAG 3998 UUGACAGUU 4637
X
CGAA ACUGUCAA UUUUAGAC
2 5
5263 GGUCUAAA CUGAUGAG 3499 UGACAGUUU 4638
X
CGAA AACUGUCA UUUAGACC
5269 AGGUCUAA CUGAUGAG 3500 GACAGUUUU 4639
X
CGAA AAACUGUC UUAGACCU
5265 CAGGUCUA CUGAUGAG 3501 ACAGUUUUU 9640
X
30
CGAA AAAACUGU UAGACCUG
5266 ACAGGUCU CUGAUGAG 3502 CAGUUUUUU 4641
X
CGAA AAAAACUG AGACCUGU
5267 CACAGGUC CUGAUGAG 3503 AGUUUUUUA 4642
X
CGAA AAAAAACU GACCUGUG
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
2Q7
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
5277 UUUUUAGU CUGAUGAG 3509 ACCUGUGUU 4693
X
CGAA ACACAGGU ACUAAAAA
5278 UUUUUUAG CUGAUGAG 3505 CCUGUGUUA 4644
X
CGAA AACACAGG CUAAAAAA
5281 CUUUUUUU CUGAUGAG 3506 GUGUUACUA 4645
X
CGAA AGUAACAC AAAAAAAG
5298 CCUUUUCC CUGAUGAG 3507 AUGAAUGUC 9696
X
CGAA ACAUUCAU GGAAAAGG
5311 ACCCUCCC CUGAUGAG 3508 AAGGGUGUU 4647
X
CGAA ACACCCUU GGGAGGGU
5323 UCUUUGUU CUGAUGAG 3509 AGGGUGGUC 4648
X
CGAA ACCACCCU AACAAAGA
5343 AACACCAU CUGAUGAG 3510 AAAGAUGUU 4649
X
CGAA ACAUCUUU AUGGUGUU
5344 AAACACCA CUGAUGAG 3511 AAGAUGUUA 4650
X
CGAA AACAUCUU UGGUGUUU
5351 UAAGUCUA CUGAUGAG 3512 UAUGGUGUU 4651
X
CGAA ACACCAUA UAGACUUA
5352 AUAAGUCU CUGAUGAG 3513 AUGGUGUUU 4652
X
CGAA AACACCAU AGACUUAU
5353 CAUAAGUC CUGAUGAG 3514 UGGUGUUUA 4653
X
CGAA AAACACCA GACUUAUG
2 5
5358 ACAACCAU CUGAUGAG 3515 UUUAGACUU 4654
X
CGAA AGUCUAAA AUGGUUGU
5359 AACAACCA CUGAUGAG 3516 UUAGACUUA 4655
X
CGAA AAGUCUAA UGGUUGUU
5364 UUUUUAAC CUGAUGAG 3517 CUUAUGGUU 4656
X
CGAA ACCAUAAG GUUAAAAA
536? ACAUUUUU CUGAUGAG 3518 AUGGUUGUU 4657
X
CGAA ACAACCAU AAAAAUGU
5368 GACAUUUU CUGAUGAG 3519 UGGUUGUUA 4658
X
CGAA AACAACCA AAAAUGUC
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
208
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
5376 CUUGAGAU CUGAUGAG 3520 AAAAAUGUC 9659
X
CGAA ACAUUUUU AUCUCAAG
5379 UGACUUGA CUGAUGAG 3521 AAUGUCAUC 4660
X
CGAA AUGACAUU UCAAGUCA
5381 CUUGACUU CUGAUGAG 3522 UGUCAUCUC 4661
X
CGAA AGAUGACA AAGUCAAG
5386 AGUGACUU CUGAUGAG 3523 UCUCAAGUC 4662
X
CGAA ACUUGAGA AAGUCACU
5391 AGACCAGU CUGAUGAG 3524 AGUCAAGUC 4663
X
CGAA ACUUGACU ACUGGUCU
5398 UGCAAACA CUGAUGAG 3525 UCACUGGUC 4664
X
CGAA ACCAGUGA UGUUUGCA
5402 CAAAUGCA CUGAUGAG 3526 UGGUCUGUU 4665
X
CGAA ACAGACCA UGCAUUUG
5403 UCAAAUGC CUGAUGAG 3527 GGUCUGUUU 9666
X
CGAA AACAGACC GCAUUUGA
5408 AUGUAUCA CUGAUGAG 3528 GUUUGCAUU 9667
X
CGAA AUGCAAAC UGAUACAU
5909 AAUGUAUC CUGAUGAG 3529 UUUGCAUUU 4668
X
CGAA AAUGCAAA GAUACAUU
5413 CAAAAAUG CUGAUGAG 3530 CAUUUGAUA 4669
X
CGAA AUCAAAUG CAUUUUUG
5417 AGUACAAA CUGAUGAG 3531 UGAUACAUU 4670
X
CGAA AUGUAUCA UUUGUACU
5418 UAGUACAA CUGAUGAG 3532 GAUACAUUU 4671
X
CGAA AAUGUAUC UUGUACUA
5419 UUAGUACA CUGAUGAG 3533 AUACAUUUU 4672
X
CGAA AAAUGUAU UGUACUAA
5420 GUUAGUAC CUGAUGAG 3534 UACAUUUUU 4673
X
CGAA AAAAUGUA GUACUAAC
5423 CUAGUUAG CUGAUGAG 3535 AUUUUUGUA 4674
X
CGAA ACAAAAAU CUAACUAG
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
209
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
5426 AUGCUAGU CUGAUGAG 3536 UUUGUACUA 9675
X
CGAA AGUACAAA ACUAGCAU
5430 UACAAUGC CUGAUGAG 3537 UACUAACUA 4676
X
CGAA AGUUAGUA GCAUUGUA
5435 AAUUUUAC CUGAUGAG 3538 ACUAGCAUU 9677
X
CGAA AUGCUAGU GUAAAAUU
5938 AAUAAUUU CUGAUGAG 3539 AGCAUUGUA 4678
X
CGAA ACAAUGCU AAAUUAUU
5493 CAUGAAAU CUGAUGAG 3540 UGUAAAAUU 4679
X
CGAA AUUUUACA AUUUCAUG
5944 UCAUGAAA CUGAUGAG 3591 GUAAAAUUA 4680
X
CGAA AAUUUUAC UUUCAUGA
5446 AAUCAUGA CUGAUGAG 3542 AAAAUUAUU 4681
X
CGAA AUAAUUUU UCAUGAUU
5447 UAAUCAUG CUGAUGAG 3543 AAAUUAUUU 4682
X
CGAA AAUAAUUU CAUGAUUA
5448 CUAAUCAU CUGAUGAG 3549 AAUUAUUUC 4683
X
2 O CGAA AAAUAAUU AUGAUUAG
5454 UAAUUUCU CUGAUGAG 3545 UUCAUGAUU 9684
X
CGAA AUCAUGAA AGAAAUUA
5455 GUAAUUUC CUGAUGAG 3546 UCAUGAUUA 9685
X
CGAA AAUCAUGA GAAAUUAC
5461 CCACAGGU CUGAUGAG 3597 UUAGAAAUU 4686
X
CGAA AUUUCUAA ACCUGUGG
5962 UCCACAGG CUGAUGAG 3548 UAGAAAUUA 4687
X
CGAA AAUUUCUA CCUGUGGA
5472 UAUACAAA CUGAUGAG 3599 CUGUGGAUA 4688
X
CGAA AUCCACAG UUUGUAUA
5474 UUUAUACA CUGAUGAG 3550 GUGGAUAUU 4689
X
CGAA AUAUCCAC UGUAUAAA
5475 UUUUAUAC CUGAUGAG 3551 UGGAUAUUU 4690
X
CGAA AAUAUCCA GUAUAAAA
CA 02324421 2000-09-26
WO 99/50403 PC'f/US99/0650'I
210
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
5978 CACUUUUA CUGAUGAG 3552 AUAUUUGUA 9691
X
CGAA ACAAAUAU UAAAAGUG
5980 CACACUUU CUGAUGAG 3553 AUUUGUAUA 9692
X
CGAA AUACAAAU AAAGUGUG
5993 AAAP~AAUU CUGAUGAG3554 UGUGAAAUA 4693
X
CGAA AUUUCACA AAUUUUUU
5497 UUAUAAAA CUGAUGAG 3555 AAAUAAAUU 4699
X
CGAA AUUUAUUU UUUUAUAA
5498 UUUAUAAA CUGAUGAG 3556 AAUAAAUUU 9695
X
CGAA AAUUUAUU UUUAUAAA
5499 UUUUAUAA CUGAUGAG 3557 AUAAAUUUU 4696
X
CGAA AAAUUUAU UUAUAAAA
5500 CUUUUAUA CUGAUGAG 3558 UAAAUUUUU 9697
X
CGAA AAAAUUUA UAUAAAAG
5501 ACUUUUAU CUGAUGAG 3559 AAAUUUUUU 4698
X
CGAA AAAAAUUU AUAAAAGU
5502 CACUUUUA CUGAUGAG 3560 AAUUUUUUA 4699
X
CGAA AAAAAAUU UAAAAGUG
5504 AACACUUU CUGAUGAG 3561 UUUUUUAUA 4700
X
CGAA AUAAAAAA AAAGUGUU
5512 AAACAAUG CUGAUGAG 3562 AAAAGUGUU 9?O1
X
CGAA ACACUUUU CAUUGUUU
2 5 5513 GAAACAAU CUGAUGAG 3563 AAAGUGUUC 4702
X
CGAA AACACUUU AUUGUUUC
5516 UACGAAAC CUGAUGAG 3564 GUGUUCAUU 4703
X
CGAA AUGAACAC GUUUCGUA
5519 UGUUACGA CUGAUGAG 3565 UUCAUUGUU 4704
X
CGAA ACAAUGAA UCGUAACA
5520 GUGUUACG CUGAUGAG 3566 UCAUUGUUU 9705
X
CGAA AACAAUGA CGUAACAC
5521 UGUGUUAC CUGAUGAG 3567 CAUUGUUUC 4706
X
CGAA AAACAAUG GUAACACA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
211
Seq. I.D. Seq. I.D.
Position RZ No. Substrate No.
5524 UGCUGUGU CUGAUGAG 3568 UGUUUCGUA 4707
X
CGAA ACGAAACA ACACAGCA
5534 ACAUAUAC CUGAUGAG 3569 CACAGCAUU 9708
X
CGAA AUGCUGUG GUAUAUGU
5537 UUCACAUA CUGAUGAG 3570 AGCAUUGUA 9709
X
CGAA ACAAUGCU UAUGUGAA
5539 GCUUCACA CUGAUGAG 3571 CAUUGUAUA 4710
X
CGAA AUACAAUG UGUGAAGC
5553 UAAUUUUA CUGAUGAG 3572 AGCAAACUC 4711
X
CGAA AGUUUGGU UAAAAUUA
5555 UAUAAUUU CUGAUGAG 3573 CAAACUCUA 9712
X
CGAA AGAGUUUG AAAUUAUA
5560 UCAUUUAU CUGAUGAG 3574 UCUAAAAUU 4713
X
CGAA AUUUUAGA AUAAAUGA
5561 GUCAUUUA CUGAUGAG 3575 CUAAAAUUA 4719
X
CGAA AAUUUUAG UAAAUGAC
5563 UUGUCAUU CUGAUGAG 3576 AAAAUUAUA 4715
X
CGAA AUAAUUUU AAUGACAA
5579 AAAUAGAU CUGAUGAG 3577 ACCUGAAUU 9716
X
CGAA AUUCAGGU AUCUAUUU
5580 GAAAUAGA CUGAUGAG 3578 CCUGAAUUA 4717
X
CGAA AAUUCAGG UCUAUUUC
5582 AUGAAAUA CUGAUGAG 3579 UGAAUUAUC 4718
X
CGAA AUAAUUCA UAUUUCAU
5589 UGAUGAAA CUGAUGAG 3580 AAUUAUCUA 4719
X
CGAA AGAUAAUU UUUCAUCA
5586 UUUGAUGA CUGAUGAG 3581 UUAUCUAUU 9720
X
CGAA AUAGAUAA UCAUCAAA
5587 UUUUGAUG CUGAUGAG 3582 UAUCUAUUU 4721
X
CGAA AAUAGAUA CAUCAAAA
5588 UUUUUGAU CUGAUGAG 3583 AUCUAUUUC 4722
X
CGAA AAAUAGAU AUCAAAAA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
212
Seq. Seq. I.D.
I.D.
Position RZ No. Substrate No.
5591 UUUUUUUU CUGAUGAG 3584 UAUUUCAUC 9723
X
CGAA AUGAAAUA AAAAAAAA
5614 UGCCCAUA CUGAUGAG 3585 AAAAAACUU 9729
X
CGAA AGUUUUUU UAUGGGCA
5615 GUGCCCAU CUGAUGAG 3586 AAAAACUUU 4725
X
CGAA AAGUUUUU AUGGGCAC
5616 UGUGCCCA CUGAUGAG 3587 AAAACUUUA 9726
X
CGAA AAAGUUUU UGGGCACA
20
30
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/Ob507
213
TABLE VI I I: HAIRPIN RIBOZYME AND TARGET SEQUENCES FOR
INTEGRIN ALPHA 6 SUBUNIT
Seq. Seq. I.D.
I.D.
PositionRZ No. Substrate No
8 CCCCGG AGAA GUCG 4727 CGACC GUC 4821
ACCAGAGAAACA X CCGGGG
GUACAUUACCUGGUA
60 UGCUGC AGAR GCAG 9728 CUGCG GUA 4822
ACCAGAGAAACA X GCAGCA
GUACAUUACCUGGUA
77 GUCCGA AGAA GCCG 4729 CGGCA GCC 4823
ACCAGAGAAACA X UCGGAC
GUACAUUACCUGGUA
83 GGCUGG AGAA GAGG 4730 CCUCG GAC 4824
ACCAGAGAAACA X CCAGCC
GUACAUUACCUGGUA
gg GCUCCG AGAA GGGU 4731 ACCCA GCC 4825
ACCAGAGAAACA X CGGAGC
GUACAUUACCUGGUA
106 UGCAGC AGAR GCCC 4732 GGGCG GCC 4826
ACCAGAGAAACA X GCUGCA
GUACAUUACCUGGUA
109 ACCUGC AGAR GCCG 4733 CGGCC GCU 4827
ACCAGAGAAACA X GCAGGU
GUACAUUACCUGGUA
122 GAGGGG AGAA GGGA 4739 UCCCC GCU 4828
ACCAGAGAAACA X CCCCUC
GUACAUUACCUGGUA
142 GCCAUG AGAA GACG 9735 CGUCC GCC 4829
ACCAGAGAAACA X CAUGGC
GUACAUUACCUGGUA
152 CCCGGC AGAA GCCA 4736 UGGCC GCC 9830
ACCAGAGAAACA X GCCGGG
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
214
Seq. Seq.
I.D. I.D.
PositionRZ No. Substrate No
155 CUGCCC AGAA GCGG 9737 CCGCC GCC 4831
ACCAGAGAAACA X GGGCAG
GUACAUUACCUGGUA
163 AAGCAC AGAA GCCC 4738 GGGCA GCU 4832
ACCAGAGAAACA X GUGCUU
GUACAUUACCUGGUA
181 CCCGCC AGAA GGUA 4739 UACCU GUC 9833
ACCAGAGAAACA X GGCGGG
GUACAUUACCUGGUA
196 AGCCGG AGAA GGAG 4740 CUCCU GUC 4834
ACCAGAGAAACA X CCGGCU
GUACAUUACCUGGUA
202 GCGCCG AGAR GGGA 9741 UCCCG GCU 4835
ACCAGAGAAACA X CGGCGC
GUACAUUACCUGGUA
212 GUUGAA AGAA GCGC 4742 GCGCA GCC 4836
ACCAGAGAAACA X UUCAAC
GUACAUUACCUGGUA
279 GCGAGA AGAA GAAG 4743 CUUCG GCU 4837
ACCAGAGAAACA X UCUCGC
GUACAUUACCUGGUA
310 UCCUCG AGAR GCAG 4744 CUGCA GCC 4838
ACCAGAGAAACA X CGAGGA
GUACAUUACCUGGUA
325 AGCAAC AGAR GCUU 4795 AAGCG GCU 4839
ACCAGAGAAACA X GUUGCU
GUACAUUACCUGGUA
3a 328 ACGAGC AGAA GCCG 4796 CGGCU GUU 4840
ACCAGAGAAACA X GCUCGU
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
215
Seq. I.D. Seq.
I.D.
PositionRZ No. Substrate No
394 CAGCUG AGAA GCCC 4797 GGGCU GUA 4841
ACCAGAGAAACA X CAGCUG
GUACAUUACCUGGUA
399 UGUCGC AGAA GUAC 4748 GUACA GCU 4842
ACCAGAGAAACA X GCGACA
GUACAUUACCUGGUA
413 CCCCCG AGAA GUGA 4749 UCACC GCC 4843
1 O ACCAGAGAAACA X CGGGGG
GUACAUUACCUGGUA
433 AACUCG AGAR GCGU 4750 ACGCG GAU 4844
ACCAGAGAAACA X CGAGUU
GUACAUUACCUGGUA
955 CGUGGG AGAR GCAU 4751 AUGCU GAC 4895
ACCAGAGAAACA X CCCACG
GUACAUUACCUGGUA
500 GCUCUG AGAA GUGA 4752 UCACC GUC 9846
ACCAGAGAAACA X CAGAGC
2 O GUACAUUACCUGGUA
899 AGCAGG AGAR GGAA 4753 UUCCU GUU 4897
ACCAGAGAAACA X CCUGCU
GUACAUUACCUGGUA
1162 UCAAAA AGAA GUGG 9754 CCACA GUA 9898
ACCAGAGAAACA X UUUUGA
GUACAUUACCUGGUA
1229 UAUUCC AGAA GCCU 4755 AGGCA GAU 4849
ACCAGAGAAACA X GGAAUA
GUACAUUACCUGGUA
1339 AGCUCC AGAA GCAA 4756 UUGCA GUU 4850
ACCAGAGAAACA X GGAGCU
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
216
Seq. I.D. Seq.
I.D.
PositionRZ No. Substrate No
1345 UCAUCA AGAR GAGC 4757 GCUCC GUA 9851
ACCAGAGAAACA X UGAUGA
GUACAUUACCUGGUA
1490 AGCAAC AGAR GGGU 4758 ACCCU GAU 9852
ACCAGAGAAACA X GUUGCU
GUACAUUACCUGGUA
1999 GGAACC AGAA GCAA 9759 UUGCU GUU 4853
ACCAGAGAAACA X GGUUCC
GUACAUUACCUGGUA
1514 UACUGA AGAA GAGA 9760 UCUCA GAU 4854
ACCAGAGAAACA X UCAGUA
GUACAUUACCUGGUA
1533 GCCGGG AGAR GAAA 4761 UUUCA GAU 4855
ACCAGAGAAACA X CCCGGC
GUACAUUACCUGGUA
1540 AUCACA AGAA GGGA 9762 UCCCG GCC 4856
ACCAGAGAAACA X UGUGAU
GUACAUUACCUGGUA
1650 AUUCAA AGAR GGAU 9763 AUCCU GUU 4857
ACCAGAGAAACA X UUGAAU
GUACAUUACCUGGUA
1673 AUAACC AGAA GGGU 4769 ACCCC GCU 4858
ACCAGAGAAACA X GGUUAU
GUACAUUACCUGGUA
1759 UUUCGA AGAA GAAC 9765 GUUCA GUU 4859
ACCAGAGAAACA X UCGAAA
GUACAUUACCUGGUA
1895 CACUGA AGAR GUUA 4766 UAACU GCC 4860
ACCAGAGAAACA X UCAGUG
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
217
Seq. Seq. I.D.
I.D.
PositionRZ No. Substrate No
1973 GGGUUC AGAA GAAU 4767 AUUCA GAU 4861
ACCAGAGAAACA X GAACCC
GUACAUUACCUGGUA
1988 AAUAUG AGAA GUCU 9768 AGACA GCU 4862
ACCAGAGAAACA X CAUAUU
GUACAUUACCUGGUA
2187 UGGAAG AGAA GUUU 4769 AAACA GCC 4863
ACCAGAGAAACA X CUUCCA
GUACAUUACCUGGUA
2245 GUUGCA AGAA GUUU 4770 AAACU GAU 4869
ACCAGAGAAACA X UGCAAC
GUACAUUACCUGGUA
2314 CAACUC AGAA GUUU 4771 AAACA GUU 4865
ACCAGAGAAACA X GAGUUG
GUACAUUACCUGGUA
2351 CUCACA AGAR GCUU 9772 AAGCU GAC 4866
ACCAGAGAAACA X UGUGAG
2 O GUACAUUACCUGGUA
2530 GAUAAA AGAA GUUC 4773 GAACU GCU 4867
ACCAGAGAAACA X UUUAUC
GUACAUUACCUGGUA
2540 UCCCGA AGAA GAUA 4779 UAUCG GUC 4868
ACCAGAGAAACA X UCGGGA
GUACAUUACCUGGUA
2585 GCCAAC AGAR GUAC 4775 GUACA GUU 4869
ACCAGAGAAACA X GUUGGC
GUACAUUACCUGGUA
2917 UUAAGA AGAR GGUA 9776 UACCA GAC 4870
ACCAGAGAAACA X UCUUAA
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
218
Seq. Seq.
I.D. I.D.
PositionRZ No. Substrate No
2928 UCACGC AGAA GUUA 4777 UAACU GUA 4871
ACCAGAGAAACA X GCGUGA
GUACAUUACCUGGUA
2958 GCGGGC AGAR GAUG 4778 CAUCA GAU 4872
ACCAGAGAAACA X GCCCGC
GUACAUUACCUGGUA
2965 CCCCGC AGAR GGCA 4779 UGCCC GCU 4873
ACCAGAGAAACA X GCGGGG
GUACAUUACCUGGUA
3092 GGCAGC AGAA GUCA 4780 UGACU GCU 4879
ACCAGAGAAACA X GCUGCC
GUACAUUACCUGGUA
3095 UUCGGC AGAA GCAG 4781 CUGCU GCU 4875
ACCAGAGAAACA X GCCGAA
GUACAUUACCUGGUA
3098 AUUUUC AGAA GCAG 4782 CUGCU GCC 4876
ACCAGAGAAACA X GAAAAU
2 O GUACAUUACCUGGUA
3164 CUGAGC AGAA GUCU 4783 AGACU GUA 4877
ACCAGAGAAACA X GCUCAG
GUACAUUACCUGGUA
3172 CCCGAA AGAA GAGC 4784 GCUCA GUA 4878
ACCAGAGAAACA X UUCGGG
GUACAUUACCUGGUA
3359 CUAUGC AGAA GAAG 9785 CUUCU GAU 4879
ACCAGAGAAACA X GCAUAG
GUACAUUACCUGGUA
3581 UUUGGG AGAA GUGA 9786 UCACA GUA 4880
ACCAGAGAAACA X CCCAAA
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
219
Seq. I.D. Seq.
I.D.
Position RZ No. Substrate No
3592 GGAAAA AGAA GUUU 4787 AAACU GCU 9881
ACCAGAGAAACA X UUUUCC
GUACAUUACCUGGUA
3633 GGAUUG AGAA GGCU 4788 AGCCU GCU 9882
ACCAGAGAAACA X CAAUCC
GUACAUUACCUGGUA
3651 UCUGAA AGAR GUCC 4789 GGACU GAU 4883
ACCAGAGAAACA X UUCAGA
GUACAUUACCUGGUA
3673 GGUUCG AGAR GUGU 4790 ACACA GUA 4884
ACCAGAGAAACA X CGAACC
GUACAUUACCUGGUA
3686 AGUUAA AGAR GUAG 4791 CUACA GUU 4885
ACCAGAGAAACA X UUAACU
GUACAUUACCUGGUA
3725 GUGCAA AGAA GGAG 4792 CUCCU GUU 4886
ACCAGAGAAACA X UUGCAC
GUACAUUACCUGGUA
3750 CAUUCC AGAA GUUU 4793 AAACU GUU 4887
ACCAGAGAAACA X GGAAUG
GUACAUUACCUGGUA
3774 AAUUAC AGAR GUUA 9799 UAACU GCC 4888
2 5 ACCAGAGAAACA X GUAAUU
GUACAUUACCUGGUA
3818 AUGUAA AGAA GCCA 4795 UGGCU GAC 4889
ACCAGAGAAACA X UUACAU
GUACAUUACCUGGUA
3gg7 CAACUG AGAA GGCC 9796 GGCCU GCC 4890
ACCAGAGAAACA X CAGUUG
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
220
Seq. Seq. I.D.
I.D.
PositionRZ No. Substrate No
3852 GAGUGC AGAR GGGC 4797 GCCCR GUU 4891
ACCAGAGAAACA X GCACUC
GUACAUUACCUGGUA
3927 GGUUAG AGAR GCCA 9798 UGGCC GUC 4892
ACCAGAGAAACA X CUAACC
GUACAUUACCUGGUA
3944 CUGCGC AGAA GGCC 4799 GGCCU GCU 4893
ACCAGAGAAACA X GCGCAG
GUACAUUACCUGGUA
3952 AUGGAC AGAA GCGC 4800 GCGCA GAC 4894
ACCAGAGAAACA X GUCCAU
GUACAUUACCUGGUA
3971 AUGUGG AGAR GCUA 4801 UAGCU GUC 4895
ACCAGAGAAACA X CCACAU
GUACAUUACCUGGUA
4026 GUUUAA AGAA GCAC 4802 GUGCU GUC 9896
ACCAGAGAAACA X UUAAAC
GUACAUUACCUGGUA
4071 GGAAAA AGAA GUAG 4803 CUACC GUC 4897
ACCAGAGAAACA X UUUUCC
GUACAUUACCUGGUA
4081 CUAGGA AGAA GGAA 4809 UUCCU GUU 4898
ACCAGAGAAACA X UCCUAG
GUACAUUACCUGGUA
4109 GACGUG AGAR GGUA 4805 UACCU GCU 4899
ACCAGAGAAACA X CACGUC
GUACAUUACCUGGUA
4165 AUUCAA AGAR GUUG 4806 CAACA GAC 4900
ACCAGAGAAACA X UUGAAU
GUACAUUACCUGGUA
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/06507
221
Seq. I.D. Seq. I.D.
PositionRZ No. Substrate No
4262 AGGGUA AGAA GGAG 9807 CUCCA GUU 9901
ACCAGAGAAACA X UACCCU
GUACAUUACCUGGUA
4426 GGUGGA AGAR GUCA 4808 UGACA GCC 4902
ACCAGAGAAACA X UCCACC
GUACAUUACCUGGUA
4600 UGAGUA AGAA GCAC 4809 GUGCG GUU 9903
ACCAGAGAAACA X UACUCA
GUACAUUACCUGGUA
4611 AUUUGC AGAA GUGA 4810 UCACU GCU 4904
ACCAGAGAAACA X GCAAAU
GUACAUUACCUGGUA
4623 UGAAUA AGAA GURU 4811 AUACU GUA 4905
ACCAGAGAAACA X UAUUCA
GUACAUUACCUGGUA
4680 UACUGG AGAA GUUU 9812 AAACU GAU 4906
ACCAGAGAAACA X CCAGUA
2 O GUACAUUACCUGGUA
4686 GUCUUA AGAA GGAU 9813 AUCCA GUA 4907
ACCAGAGAAACA X UAAGAC
GUACAUUACCUGGUA
4769 UGGGAA AGAA GAUA 4819 UAUCU GUA 9908
2 5 ACCAGAGAAACA X UUCCCA
GUACAUUACCUGGUA
4895 AAAAAA AGAA GCUU 4815 AAGCU GAU 4909
ACCAGAGAAACA X UUUUUU
GUACAUUACCUGGUA
30 5015 ACUACA AGAA GUGU 9816 ACACA GUU 4910
ACCAGAGAAACA X UGUAGU
GUACAUUACCUGGUA
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Seq. Seq.
I.D. I.D.
PositionRZ No. Substrate No
5030 CAAAAC AGAA GUGG 4817 CCACU GUU 4911
ACCAGAGAAACA X GUUUUG
GUACAUUACCUGGUA
5188 GCAAGA AGAA GAGA 4818 UCUCA GUU 9912
ACCAGAGAAACA X UCUUGC
GUACAUUACCUGGUA
5259 CUAAAA AGAA GUCA 4819 UGACA GUU 4913
ACCAGAGAAACA X UUUUAG
GUACAUUACCUGGUA
5399 AAUGCA AGAR GACC 4820 GGUCU GUU 4914
ACCAGAGAAACA X UGCAUU
GUACAUUACCUGGUA
20
30
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TABLE IX: HAMMERHEAD RIBOZYME AND TARGET SEQUENCES FOR
INTEGRIN SUBUNIT BETA 3
Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
17 GAGGGCAA CUGAUGAG X 4915 GAUGUGGUC 5702
CGAA
ACCACAUC UUGCCCUC
19 UUGAGGGC CUGAUGAG X 4916 UGUGGUCUU 5703
CGAA
AGACCACA GCCCUCAA
25 UACCUGUU CUGAUGAG X 4917 CUUGCCCUC 5704
CGAA
AGGGCAAG AACAGGUA
33 AGACUACC CUGAUGAG X 4918 CAACAGGUA 5705
CGAA
ACCUGUUG GGUAGUCU
37 CGGUAGAC CUGAUGAG X 4919 AGGUAGGUA 5706
CGAA
ACCUACCU GUCUACCG
40 UUCCGGUA CUGAUGAG X 4920 UAGGUAGUC 5707
CGAA
ACUACCUA UACCGGAA
q2 UUUUCCGG CUGAUGAG X 9921 GGUAGUCUA 5708
CGAA
AGACUACC CCGGAAAA
58 UCUUGCCU CUGAUGAG X 4922 ACCAAACUA 5709
CGAA
AGUUUGGU AGGCAAGA
74 UAUUCACU CUGAUGAG X 4923 AAAAAAAUU 5710
CGAA
AUUUUUUU AGUGAAUA
75 UUAUUCAC CUGAUGAG X 9924 AAAAAAUUA 5711
CGAA
AAUUUUUU GUGAAUAA
82 UCCUUUAU CUGAUGAG X 4925 UAGUGAAUA 5712
CGAA
AUUCACUA AUAAAGGA
85 CAGUCCUU CUGAUGAG X 4926 UGAAUAAUA 5713
CGAA
AUUAUUCA AAGGACUG
101 CUUCUCUG CUGAUGAG X 9927 GAACCGGUU 5719
CGAA
ACCGGUUC CAGAGAAG
102 CCUUCUCU CUGAUGAG X 4928 AACCGGUUC 5715
CGAA
AACCGGUU AGAGAAGG
119 AUCUGCUG CUGAUGAG X 9929 GAAGGCAUU 5716
CGAA
AUGCCUUC CAGCAGAU
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
115 CAUCUGCU CUGAUGAG X 4930 AAGGCAUUC 5717
CGAA
AAUGCCUU AGCAGAUG
125 GACUGGCA CUGAUGAG X 4931 GCAGAUGUU 5718
CGAA
ACAUCUGC UGCCAGUC
126 UGACUGGC CUGAUGAG X 4932 CAGAUGUUU 5719
CGAA
AACAUCUG GCCAGUCA
133 AUUCAUUU CUGAUGAG X 4933 UUGCCAGUC 5720
CGAA
ACUGGCAA AAAUGAAU
142 CACACUUU CUGAUGAG X 9939 AAAUGAAUU 5721
CGAA
AUUCAUUU AAAGUGUG
143 UCACACUU CUGAUGAG X 9935 AAUGAAUUA 5722
CGAA
AAUUCAUU AAGUGUGA
164 ACUACCUC CUGAUGAG X 9936 AUGAAACUC 5723
CGAA
AGUUUCAU GAGGUAGU
170 UCACCCAC CUGAUGAG X 4937 CUCGAGGUA 5724
CGAA
ACCUCGAG GUGGGUGA
185 AUUCUUGG CUGAUGAG X 4938 GAAUGUGUC 5725
CGAA
2 O ACACAUUC CCAAGAAU
194 UUUCGCUG CUGAUGAG X 9939 CCAAGAAUC 5726
CGAA
AUUCUUGG CAGCGAAA
209 UCCUGGGA CUGAUGAG X 9940 AACAGGGUC 5727
CGAA
ACCCUGUU UCCCAGGA
211 CCUCCUGG CUGAUGAG X 4991 CAGGGUCUC 5728
CGAA
AGACCCUG CCAGGAGG
235 CCUCUCCG CUGAUGAG X 4942 GGAAGGGUC 5729
CGAA
ACCCUUCC CGGAGAGG
255 AAGGCCAG CUGAUGAG X 4943 CACAGGCUC 5730
CGAA
AGCCUGUG CUGGCCUU
263 UGCUUAGA CUGAUGAG X 9944 CCUGGCCUU 5731
GGAA
AGGCCAGG UCUAAGCA
269 GUGCUUAG CUGAUGAG X 4995 CUGGCCUUU 5732
CGAA
AAGGCCAG CUAAGCAC
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
265 UGUGCUUA CUGAUGAG X 4946 UGGCCUUUC 5733
CGAA
AAAGGCCA UAAGCACA
267 GGUGUGCU CUGAUGAG X 4947 GCCUUUCUA 5734
CGAA
AGAAAGGC AGCACACC
287 GGGUCCGC CUGAUGAG X 4948 UGCCCAGUC 5735
CGAA
ACUGGGCA GCGGACCC
337 CCCACGAG CUGAUGAG X 4949 AGGCGGGUC 5736
CGAA
ACCCGCCU CUCGUGGG
390 UCGCCCAC CUGAUGAG X 4950 CGGGUCCUC 5737
CGAA
AGGACCCG GUGGGCGA
378 UGGGAAAC CUGAUGAG X 4951 GGAGCAAUA 5738
CGAA
AUUGCUCC GUUUCCCA
381 CGGUGGGA CUGAUGAG X 4952 GCAAUAGUU 5739
CGAA
ACUAUUGC UCCCACCG
382 GCGGUGGG CUGAUGAG X 4953 CAAUAGUUU 5740
CGAA
AACUAUUG CCCACCGC
383 AGCGGUGG CUGAUGAG X 4954 AAUAGUUUC 5741
CGAA
2 O AAACUAUU CCACCGCU
392 CUGAGAGG CUGAUGAG X 9955 CCACCGCUC 5742
CGAA
AGCGGUGG CCUCUCAG
396 GCGCCUGA CUGAUGAG X 4956 CGCUCCCUC 5743
CGAA
AGGGAGCG UCAGGCGC
2 5 3gg CUGCGCCU CUGAUGAG X 4957 CUCCCUCUC 5744
CGAA
AGAGGGAG AGGCGCAG
910 CUUCUCUA CUGAUGAG X 4958 CGCAGGGUC 5745
CGAA
ACCCUGCG UAGAGAAG
412 CGCUUCUC CUGAUGAG X 4959 CAGGGUCUA 5796
CGAA
30
AGACCCUG GAGAAGCG
930 CUUCUCUA CUGAUGAG X 4960 GAGGGGAUC 5747
CGAA
AUCCCCUC UAGAGAAG
432 GGCUUCUC CUGAUGAG X 4961 GGGGAUCUA 5748
CGAA
AGAUCCCC GAGAAGCC
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
461 GGGCCGCG CUGAUGAG X 4962 GCGCGAGUC 5749
CGAA
ACUCGCGC CGCGGCCC
477 UGGGACGC CUGAUGAG X 4963 CGCCCCGUU 5750
CGAA
ACGGGGCG GCGUCCCA
482 GUGGGUGG CUGAUGAG X 4964 CGUUGCGUC 5751
CGAA
ACGCAACG CCACCCAC
496 GGGGAGGG CUGAUGAG X 9965 CACCG.CGUC 5752
CGAA
ACGCGGUG CCCUCCCC
501 GGGGAGGG CUGAUGAG X 4966 CGUCCCCUC 5753
CGAA
AGGGGACG CCCUCCCC
506 CGGGAGGG CUGAUGAG X 4967 CCUCCCCUC 5754
CGAA
AGGGGAGG CCCUCCCG
511 CGCAGCGG CUGAUGAG X 4968 CCUCCCCUC 5755
CGAA
AGGGGAGG CCGCUGCG
614 GUCGCCCA CUGAUGAG X 4969 CGGCCGCUC 5756
CGAA
AGCGGCCG UGGGCGAC
653 CCUACGCC CUGAUGAG X 4970 GCGGGCGUU 5757
CGAA
2~ ACGCCCGC GGCGUAGG
659 UCACCUCC CUGAUGAG X 4971 GUUGGCGUA 5758
CGAA
ACGCCAAC GGAGGUGA
676 CCGAGCCG CUGAUGAG X 4972 GUGAGGCUC 5759
CGAA
AGCCUCAC CGGCUCGG
682 ACGCUGCC CUGAUGAG X 4973 CUCCGGCUC 5760
CGAA
AGCCGGAG GGCAGCGU
691 GCAGCUGC CUGAUGAG X 4974 GGCAGCGUC 5761
CGAA
ACGCUGCC GCAGCUGC
708 GGGGCGCA CUGAUGAG X 4975 CCCAGGAUC 5762
CGAA
AUCCUGGG UGCGCCCC
720 CGCAACUU CUGAUGAG X 4976 GCCCCGGUC 5763
CGAA
ACCGGGGC AAGUUGCG
725 AAGUCCGC CUGAUGAG X 9977 GGUCAAGUU 5764
CGAA
ACUUGACC GCGGACUU
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
733 CCGGCUCC CUGAUGAG X 9978 UGCGGACUU 5765
CGAA
AGUCCGCA GGAGCCGG
760 GACGNGCG CUGAUGAG X 4979 GGACUGGUC 5766
CGAA
ACCAGUCC CGCNCGUC
768 CCCACGCA CUGAUGAG X 4980 CCGCNCGUC 5767
CGAA
ACGNGCGG UGCGUGGG
780 GACACGNG CUGAUGAG X 4981 GUGGGAAUN 5768
CGAA
AUUCCCAC CNCGUGUC
788 CCAGCCAG CUGAUGAG X 4982 NCNCGUGUC 5769
CGAA
ACACGNGN CUGGCUGG
803 CCGGNUCC CUGAUGAG X 4983 GGCNCGGUC 5770
CGAA
ACCGNGCC GGANCCGG
825 GGGCCAGG CUGAUGAG X 9984 GGGNACCUU 5771
CGAA
AGGUNCCC CCUGGCCC
826 CGGGCCAG CUGAUGAG X 9985 GGNACCUUC 5772
CGAA
AAGGUNCC CUGGCCCG
877 UCUCGGAG CUGAUGAG X 4986 GAGCGGGUC 5773
CGAA
2 O ACCCGCUC CUCCGAGA
880 GCGUCUCG CUGAUGAG X 4987 CGGGUCCUC 5774
CGAA
AGGACCCG CGAGACGC
898 GCCUGGCU CUGAUGAG X 4988 GAAGCCAUC 5775
CGAA
AUGGCUUC AGCCAGGC
2 5 g16 CGGCCGGG CUGAUGAG X 4989 GANNNCCUU 5776
CGAA
AGGNNNUC CCCGGCCG
917 GCGGCCGG CUGAUGAG X 4990 ANNNCCUUC 5777
CGAA
AAGGNNNU CCGGCCGC
959 GGCUCAGA CUGAUGAG X 4991 GGGCGCAUC 5778
CGAA
30
AUGCGCCC UCUGAGCC
956 GGGGCUCA CUGAUGAG X 4992 GCGCAUCUC 5779
CGAA
AGAUGCGC UGAGCCCC
970 CCCCGGGU CUGAUGAG X 9993 CCCGCGCUC 5780
CGAA
AGCGCGGG ACCCGGGG
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
989 NCACCCGC CUGAUGAG X 4994 GCGCGCGUC 5781
CGAA
ACGCGCGC GCGGGUGN
999 CCGACCAG CUGAUGAG X 4995 CGGGUGNUC 5782
CGAA
ANCACCCG CUGGUCGG
1005 CUUGGNCC CUGAUGAG X 4996 NUCCUGGUC 5783
CGAA
ACCAGGAN GGNCCAAG
1048 ACCCCCGG CUGAUGAG X 4997 GUGGGGCUU 5784
CGAA
AGCCCCAC CCGGGGGU
1049 AACCCCCG CUGAUGAG X 4998 UGGGGCUUC 5785
CGAA
AAGCCCCA CGGGGGUU
1057 GCGGGAAC CUGAUGAG X 4999 CCGGGGGUU 5786
CGAA
ACCCCCGG GUUCCCGC
1060 GGGGCGGG CUGAUGAG X 5000 GGGGUUGUU 5787
CGAA
ACAACCCC CCCGCCCC
1061 AGGGGCGG CUGAUGAG X 5001 GGGUUGUUC 5788
CGAA
AACAACCC CCGCCCCU
1070 CCUCUGCC CUGAUGAG X 5002 CCGCCCCUU 5789
CGAA
2O AGGGGCGG GGCAGAGG
1089 CAGGAAGU CUGAUGAG X 5003 UGCCCUGUA 5790
CGAA
ACAGGGCA ACUUCCUG
1093 CACCCAGG CUGAUGAG X 5004 CUGUAACUU 5791
CGAA
AGUUACAG CCUGGGUG
1094 UCACCCAG CUGAUGAG X 5005 UGUAACUUC 5792
CGAA
AAGUUACA CUGGGUGA
1123 GAAAUGUA CUGAUGAG X 5006 GCGCGGGUU 5793
CGAA
ACCCGCGC UACAUUUC
1124 GGAAAUGU CUGAUGAG X 5007 CGCGGGUUU 5799
CGAA
AACCCGCG ACAUUUCC
1125 GGGAAAUG CUGAUGAG X 5008 GCGGGUUUA 5795
CGAA
AAACCCGC CAUUUCCC
1129 UGUGGGGA CUGAUGAG X 5009 GUUUACAUU 5796
CGAA
AUGUAAAC UCCCCACA
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1130 AUGUGGGG CUGAUGAG X 5010 UUUACAUUU 5797
CGAA
AAUGUAAA CCCCACAU
1131 AAUGUGGG CUGAUGAG X 5011 UUACAUUUC 5798
CGAA
AAAUGUAA CCCACAUU
1139 AAAUUGGA CUGAUGAG X 5012 CCCCACAUU 5799
CGAA
AUGUGGGG UCCAAUUU
1140 GAAAUUGG CUGAUGAG X 5013 CCCACAUUU 5800
CGAA
AAUGUGGG CCAAUUUC
1141 AGAAAUUG CUGAUGAG X 5014 CCACAUUUC 5801
CGAA
AAAUGUGG CAAUUUCU
1146 ACAGGAGA CUGAUGAG X 5015 UUUCCAAUU 5802
CGAA
AUUGGAAA UCUCCUGU
Z5 1147 AACAGGAG CUGAUGAG X 5016 UUCCAAUUU 5803
CGAA
AAUUGGAA CUCCUGUU
1148 UAACAGGA CUGAUGAG X 5017 UCCAAUUUC 5809
CGAA
AAAUUGGA UCCUGUUA
1150 CGUAACAG CUGAUGAG X 5018 CAAUUUCUC 580.5
CGAA
AGAAAUUG CUGUUACG
1155 GAAAGCGU CUGAUGAG X 5019 UCUCCUGUU 5806
CGAA
ACAGGAGA ACGCUUUC
1156 AGAAAGCG CUGAUGAG X 5020 CUCCUGUUA 5807
CGAA
AACAGGAG CGCUUUCU
2 5 1161 UCUGGAGA CUGAUGAG X 5021 GUUACGCUU 5808
CGAA
AGCGUAAC UCUCCAGA
1162 UUCUGGAG CUGAUGAG X 5022 UUACGCUUU 5809
CGAA
AAGCGUAA CUCCAGAA
1163 CUUCUGGA CUGAUGAG X 5023 UACGCUUUC 5810
CGAA
3 O
~AGCGUA UCCAGAAG
1165 ACCUUCUG CUGAUGAG X 5029 CGCUUUCUC 5811
CGAA
AGAAAGCG CAGAAGGU
1179 AAAGAAAA CUGAUGAG X 5025 CAGAAGGUU 5812
CGAA
ACCUUCUG UUUUCUUU
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1175 GAAAGAAA CUGAUGAG X 5026 AGAAGGUUU 5813
CGAA
AACCUUCU UUUCUUUC
1176 GGAAAGAA CUGAUGAG X 5027 GAAGGUUUU 5814
CGAA
AAACCUUC UUCUUUCC
1177 AGGAAAGA CUGAUGAG X 5028 AAGGUUUUU 5815
CGAA
AAAACCUU UCUUUCCU
1178 AAGGAAAG CUGAUGAG X 5029 AGGUUUUUU 5816
CGAA
AAAAACCU CUUUCCUU
1179 AAAGGAAA CUGAUGAG X 5030 GGUUUUUUC 5817
CGAA
AAAAAACC UUUCCUUU
1181 AAAAAGGA CUGAUGAG X 5031 UUUUUUCUU 5818
CGAA
AGAAAAAA UCCUUUUU
1182 AAAAAAGG CUGAUGAG X 5032 UUUUUCUUU 5819
CGAA
AAGAAAAA CCUUUUUU
1183 GAAAAAAG CUGAUGAG X 5033 UUUUCUUUC 5820
CGAA
AAAGAAAA CUUUUUUC
1186 AAAGAAAA CUGAUGAG X 5034 UCUUUCCUU 5821
CGAA
2 d AGGAAAGA UUUUCUUU
1187 GAAAGAAA CUGAUGAG X 5035 CUUUCCUUU 5822
CGAA
AAGGAAAG UUUCUUUC
1188 AGAAAGAA CUGAUGAG X 5036 UUUCCUUUU 5823
CGAA
AAAGGAAA UUCUUUCU
2 5
1189 AAGAAAGA GUGAUGAG X 5037 UUCCUUUUU 5824
CGAA
AAAAGGAA UCUUUCUU
1190 AAAGAAAG CUGAUGAG X 5038 UCCUUUUUU 5825
CGAA
AAAAAGGA CUUUCUUU
1191 GAAAGAAA CUGAUGAG X 5039 CCUUUUUUC 5826
CGAA
3 0
~ppp~GG UUUCUUUC
1193 AAGAAAGA CUGAUGAG X 5040 UUUUUUCUU 5827
CGAA
AGAAAAAA UCUUUCUU
1194 AAAGAAAG CUGAUGAG X 5041 UUUUUCUUU 5828
CGAA
AAGAAAAA CUUUCUUU
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1195 GAAAGAAA CUGAUGAG X 5042 UUUUCUUUC 5829
CGAA
AAAGAAAA UUUCUUUC
1197 AAGAAAGA CUGAUGAG X 5043 UUCUUUCUU 5830
CGAA
AGAAAGAA UCUUUCUU
1198 AAAGAAAG CUGAUGAG X 5044 UCUUUCUUU 5831
CGAA
AAGAAAGA CUUUCUUU
1199 AAAAGAAA CUGAUGAG X 5045 CUUUCUUUC 5832
CGAA
AAAGAAAG UUUCUUUU
1201 AAAAAAGA CUGAUGAG X 5046 UUCUUUCUU 5833
CGAA
AGAAAGAA UCUUUUUU
1202 AAAAAAAG CUGAUGAG X 5047 UCUUUCUUU 5834
CGAA
AAGAAAGA CUUUUUUU
1203 UAAAAAAA CUGAUGAG X 5048 CUUUCUUUC 5835
CGAA
AAAGAAAG UUUUUUUA
1205 GGUAAAAA CUGAUGAG X 5049 UUCUUUCUU 5836
CGAA
AGAAAGAA UUUUUACC
1206 AGGUAAAA CUGAUGAG X 5050 UCUUUCUUU 5837
CGAA
2 0 AAGAAAGA UUUUACCU
1207 AAGGUAAA CUGAUGAG X 5051 CUUUCUUUU 5838
CGAA
AAAGAAAG UUUACCUU
1208 GAAGGUAA CUGAUGAG X 5052 UUUCUUUUU 5839
CGAA
AAAAGAAA UUACCUUC
1209 UGAAGGUA CUGAUGAG X 5053 UUCUUUUUU 5840
CGAA
AAAAAGAA UACCUUCA
1210 UUGAAGGU CUGAUGAG X 5054 UCUUUUUUU 5841
CGAA
AAAAAAGA ACCUUCAA
1211 GUUGAAGG CUGAUGAG X 5055 CUUUUUUUA 5842
CGAA
SAG CCUUCAAC
1215 GUAUGUUG CUGAUGAG X 5056 UUUUACCUU 5843
CGAA
AGGUAAP.A CAACAUAC
1216 AGUAUGUU CUGAUGAG X 5057 UUUACCUUC 5844
CGAA
AAGGUAAA AACAUACU
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1222 CGCAGGAG CUGAUGAG X 5058 UUCAACAUA 5845
CGAA
AUGUUGAA CUCCUGCG
2225 CCCCGCAG CUGAUGAG X 5059 AACAUACUC 5846
CGAA
AGUAUGUU CUGCGGGG
1235 UCCAAAAC CUGAUGAG X 5060 UGCGGGGUU 5847
CGAA
ACCCCGCA GUUUUGGA
1238 UGCUCCAA CUGAUGAG X 5061 GGGGUUGUU 5848
CGAA
ACAACCCC UUGGAGCA
1239 CUGCUCCA CUGAUGAG X 5062 GGGUUGUUU 5849
CGAA
AACAACCC UGGAGCAG
1240 CCUGCUCC CUGAUGAG X 5063 GGUUGUUUU 5850
CGAA
AAACAACC GGAGCAGG
1257 AGGAGGCA CUGAUGAG X 5064 AUGAGGCUU 5851
CGAA
AGCCUCAU UGCCUCCU
1258 GAGGAGGC CUGAUGAG X 5065 UGAGGCUUU 5852
CGAA
AAGCCUCA GCCUCCUC
1263 CACUGGAG CUGAUGAG X 5066 CUUUGCCUC 5853
CGAA
2 O AGGCAAAG CUCCAGUG
1266 GGACACUG CUGAUGAG X 5067 UGCCUCCUC 5859
CGAA
AGGAGGCA CAGUGUCC
1273 CACCUGGG CUGAUGAG X 5068 UCCAGUGUC 5855
CGAA
ACACUGGA CCCAGGUG
1294 UGGGAGCA CUGAUGAG X 5069 CGGUGCCUC 5856
CGAA
AGGCACCG UGCUCCCA
1299 UGCCCUGG CUGAUGAG X 5070 CCUCUGCUC 5857
CGAA
AGCAGAGG CCAGGGCA
1327 ACACUAGA CUGAUGAG X 5071 CGAAAAAUC 5858
CGAA
AUUUUUCG UCUAGUGU
1329 AUACACUA CUGAUGAG X 5072 AAAAAUCUC 5859
CGAA
AGAUUUUU UAGUGUAU
1331 GAAUACAC CUGAUGAG X 5073 AAAUCUCUA 5860
CGAA
AGAGAUUU GUGUAUUC
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Posi- Seq. I.D. Seq. I.D.
'
tion RZ No Substrate No.
.
1336 UCCCCGAA CUGAUGAG X 5074 UCUAGUGUA 5861
CGAA
ACACUAGA UUCGGGGA
1338 GUUCCCCG CUGAUGAG X 5075 UAGUGUAUU 5862
CGAA
AUACACUA CGGGGAAC
1339 GGUUCCCC CUGAUGAG X 5076 AGUGUAUUC 5863
CGAA
AAUACACU GGGGAACC
1359 GCCCAAGG CUGAUGAG X 5077 AAAAGGCUC 5864
CGAA
AGCCUUUU CCUUGGGC
1363 ACCGGCCC CUGAUGAG X 5078 GGCUCCCUU 5865
CGAA
AGGGAGCC GGGCCGGU
1377 AAGCCAAG CUGAUGAG X 5079 GGUGGGAUC 5866
CGAA
AUCCCACC CUUGGCUU
1380 ACAAAGCC CUGAUGAG X 5080 GGGAUCCUU 5867
CGAA
AGGAUCCC GGCUUUGU.
1385 CAGAGACA CUGAUGAG X 5081 CCUUGGCUU 5868
CGAA
AGCCAAGG UGUCUCUG
1386 GCAGAGAC CUGAUGAG X 5082 CUUGGCUUU 5869
CGAA
2~ AAGCCAAG GUCUCUGG
1389 CAGCCAGA CUGAUGAG X 5083 GGCUUUGUC 5870
CGAA
ACAAAGCC UCUGGCUG
1391 AGCAGCCA CUGAUGAG X 5084 CUUUGUCUC 5871
CGAA
AGACAAAG UGGCUGCU
2 5 1411 UGACGGCU CUGAUGAG X 5085 CACACCGUC 5872
CGAA
ACGGUGUG AGCCGUCA
1418 AUUGCCCU CUGAUGAG X 5086 UCAGCCGUC 5873
CGAA
ACGGCUGA AGGGCAAU
1927 CGAAUGCC CUGAUGAG X 5087 AGGGCAAUU 5874
CGAA
30 AUUGCCCU GGCAUUCG
1433 AGAGGCCG CUGAUGAG X 5088 AUUGGCAUU 5875
CGAA
AUGCCAAU CGGCCUCU
1434 AAGAGGCC CUGAUGAG X 5089 UUGGCAUUC 5876
CGAA
AAUGCCAA GGCCUCUU
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1940 GUACCAAA CUGAUGAG X 5090 UUCGGCCUC 5877
CGAA
AGGCCGAA UUUGGUAC
1442 CAGUACCA CUGAUGAG X 5091 CGGCCUCUU 5878
CGAA
AGAGGCCG UGGUACUG
1493 CCAGUACC CUGAUGAG X 5092 GGCCUCUUU 5879
CGAA
AAGAGGCC GGUACUGG
1497 GUCCCCAG CUGAUGAG X 5093 UCUUUGGUA 5880
CGAA
ACCAAAGA CUGGGGAC
1991 CGGGCAGC CUGAUGAG X 5099 CCCGGGGUU 5881
CGAA
ACCCCGGG GCUGCCCG
1504 UCAGAGAG CUGAUGAG X 5095 CCCGUGGUC 5882
CGAA
ACCACGGG CUCUCUGA
1507 GACUCAGA CUGAUGAG X 5096 GUGGUCCUC 5883
CGAA
AGGACCAC UCUGAGUC
1509 AGGACUCA CUGAUGAG X 5097 GGUCCUCUC 5884
CGAA
AGAGGACC UGAGUCCU
1515 UCACCAAG CUGAUGAG X 5098 CUCUGAGUC 5885
CGAA
ACUCAGAG CUUGGUGA
1518 AAAUCACC CUGAUGAG X 5099 UGAGUCCUU 5886
CGAA
AGGACUCA GGUGAUUU
1525 CCAGGCAA CUGAUGAG X 5100 UUGGUGAUU 5887
CGAA
AUCACCAA UUGCCUGG
1526 CCCAGGCA CUGAUGAG X 5101 UGGUGAUUU 5888
CGAA
AAUCACCA UGCCUGGG
1527 GCCCAGGC CUGAUGAG X 5102 GGUGAUUUU 5889
CGAA
AAAUCACC GCCUGGGC
1554 CAGACCAG CUGAUGAG X 5103 CCCUGGCUC 5890
CGAA
AGCCAGGG CUGGUCUG
1560 CCCCAGCA CUGAUGAG X 5104 CUCCUGGUC 5891
CGAA
ACCAGGAG UGCUGGGG
1575 CUGAGGCA CUGAUGAG X 5105 GGCCGCCUC 5892
CGAA
AGGCGGCC UGCCUCAG
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
15$1 CAUCCUCU CUGAUGAG X 5106 CUCUGCCUC 5893
CGAA
AGGCAGAG AGAGGAUG
1606 AAAAUACU CUGAUGAG X 5107 GUGCAUGUA 5894
CGAA
ACAUGCAC AGUAUUUU
1610 AUUAAAAA CUGAUGAG X 5108 AUGUAAGUA 5895
CGAA
ACUUACAU UUUUUAAU
1612 UUAUUAAA CUGAUGAG X 5109 GUAAGUAUU 5896
CGAA
AUACUUAC UUUAAUAA
1613 UUUAUUAA CUGAUGAG X 5110 UAAGUAUUU 5897
CGAA
AAUACUUA UUAAUAAA
1614 UUUUAUUA CUGAUGAG X 5111 AAGUAUUUU 5898
CGAA
AAAUACUU UAAUAAAA
1615 UUUUUAUU CUGAUGAG X 5112 AGUAUUUUU 5899
CGAA
AP.AAUACU AAUAAAAA
1616 GUUUUUAU CUGAUGAG X 5113 GUAUUUUUA 5900
CGAA
AAAAAUAC AUAAAAAC
1619 ACAGUUUU CUGAUGAG X 5114 UUUUUAAUA 5901
CGAA
AUUAAAAA AAAACUGU
1628 ACGAGUAC CUGAUGAG X 5115 AAAACUGUA 5902
CGAA
ACAGUUUU GUACUCGU
1631 UUUACGAG CUGAUGAG X 5116 ACUGUAGUA 5903
CGAA
ACUACAGU CUCGUAAA
1634 UGUUUUAC CUGAUGAG X 5117 GUAGUACUC 5904
CGAA
AGUACUAC GUAAAACA
1637 GAUUGUUU CUGAUGAG X 5118 GUACUCGUA 5905
CGAA
ACGAGUAC AAACAAUC
1645 AGGGUGUA CUGAUGAG X 5119 AAAACAAUC 5906
CGAA
AUUGUUUU UACACCCU
1647 GCAGGGUG CUGAUGAG X 5120 AACAAUCUA 5907
CGAA
AGAUUGUU CACCCUGC
1665 AAAUAACA CUGAUGAG X 5121 GAAGGGAUU 5908
CGAA
AUCCCUUC UGUUAUUU
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1666 AAAAUAAC CUGAUGAG X 5122 AAGGGAUUU 5909
CGAA
AAUCCCUU GUUAUUUU
1669 AAUAAAAU CUGAUGAG X 5123 GGAUUUGUU 5910
CGAA
ACAAAUCC AUUUUAUU
1670 AAAUAAAA CUGAUGAG X 5129 GAUUUGUUA 5911
CGAA
AACAAAUC UUUUAUUU
1672 UAAAAUAA CUGAUGAG X 5125 UUUGUUAUU 5912
CGAA
AUAACAAA UUAUUUUA
1673 AUAAAAUA CUGAUGAG X 5126 UUGUUAUUU 5913
CGAA
AAUAACAA UAUUUUAU
1674 AAUAAAAU CUGAUGAG X 5127 UGUUAUUUU 5919
CGAA
AAAUAACA AUUUUAUU
1675 UAAUAAAA CUGAUGAG X 5128 GUUAUUUUA 5915
CGAA
AAAAUAAC UUUUAUUA
1677 AAUAAUAA CUGAUGAG X 5129 UAUUUUAUU 5916
CGAA
AUAAAAUA UUAUUAUU
1678 AAAUAAUA CUGAUGAG X 5130 AUUUUAUUU 5917
CGAA
2 O p,AU~U UAUUAUUU
1679 UAAAUAAU CUGAUGAG X 5131 UUUUAUUUU 5918
CGAA
AAAUAAAA AUUAUUUA
1680 AUAAAUAA CUGAUGAG X 5132 UUUAUUUUA 5919
CGAA
AAAAUAAA UUAUUUAU
2 5 1682 AAAUAAAU CUGAUGAG X 5133 UAUUUUAUU 5920
CGAA
AUAAAAUA AUUUAUUU
1683 UAAAUAAA CUGAUGAG X 5134 AUUUUAUUA 5921
CGAA
AAUAAAAU UUUAUUUA
1685 AAUAAAUA CUGAUGAG X 5135 UUUAUUAUU 5922
CGAA
30
AUAAUAAA UAUUUAUU
1686 AAAUAAAU CUGAUGAG X 5136 UUAUUAUUU 5923
CGAA
AAUAAUAA AUUUAUUU
1687 UAAAUAAA CUGAUGAG X 5137 UAUUAUUUA 5924
CGAA
AAAUAAUA UUUAUUUA
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1689 AAUAAAUA CUGAUGAG X 5138 UUAUUUAUU 5925
CGAA
AUAAAUAA UAUUUAUU
1690 AAAUAAAU CUGAUGAG X 5139 UAUUUAUUU 5926
CGAA
AAUAAAUA AUUUAUUU
1691 UAAAUAAA CUGAUGAG X 5140 AUUUAUUUA 5927
CGAA
AAAUAAAU UUUAUUUA
1693 AAUAAAUA CUGAUGAG X 5141 UUAUUUAUU 5928
CGAA
1 O AUAAAU~ UAUUUAUU
1694 AAAUAAAU CUGAUGAG X 5142 UAUUUAUUU 5929
CGAA
AAUAAAUA AUUUAUUU
1695 UAAAUAAA CUGAUGAG X 5143 AUUUAUUUA 5930
CGAA
AAAUAAAU UUUAUUUA
15 1697 AAUAAAUA CUGAUGAG X 5144 UUAUUUAUU 5931
CGAA
AUAAAUAA UAUUUAUU
1698 AAAUAAAU CUGAUGAG X 5145 UAUUUAUUU 5932
CGAA
AAUAAAUA AUUUAUUU
1699 AAAAUAAA CUGAUGAG X 5146 AUUUAUUUA 5933
CGAA
2 O ~Up~,pU UUUAUUUU
1701 CAAAAAUA CUGAUGAG X 5197 UUAUUUAUU 5939
CGAA
AUAAAUAA UAUUUUUG
1702 UCAAAAAU CUGAUGAG X 5148 UAUUUAUUU 5935
CGAA
AAUAAAUA AUUUUUGA
25 1703 CUCAAAAA CUGAUGAG X 5199 AUUUAUUUA 5936
CGAA
AAAUAAAU UUUUUGAG
1705 GUCUCAAA CUGAUGAG X 5150 UUAUUUAUU 5937
CGAA
AUAAAUAA UUUGAGAC
1706 CGUCUCAA CUGAUGAG X 5151 UAUUUAUUU 5938
CGAA
3 O
~Up,~.~UA UUGAGACG
1707 CCGUCUCA CUGAUGAG X 5152 AUUUAUUUU 5939
CGAA
AAAUAAAU UGAGACGG
1708 UCCGUCUC CUGAUGAG X 5153 UUUAUUUUU 5940
CGAA
~U~A GAGACGGA
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1719 CAGAGCAA CUGAUGAG X 5154 GACGGAGUC 5941
CGAA
ACUCCGUC UUGCUCUG
1721 GACAGAGC CUGAUGAG X 5155 CGGAGUCUU 5942
CGAA
AGACUCCG GCUCUGUC
1725 GGGCGACA CUGAUGAG X 5156 GUCUUGCUC 5943
CGAA
AGCAAGAC UGUCGCCC
1729 GCCUGGGC CUGAUGAG X 5157 UGCUCUGUC 5944
CGAA
ACAGAGCA GCCCAGGC
1756 GAGCCGAG CUGAUGAG X 5158 UGGUGGGUU 5945
CGAA
ACCCACCA CUCGGCUC
1757 UGAGCCGA CUGAUGAG X 5159 GGUGGGUUC 5946
CGAA
AACCCACC UCGGCUCA
1759 AGUGAGCC CUGAUGAG X 5160 UGGGUUCUC 5997
CGAA
AGAACCCA GGCUCACU
1764 GUUGCAGU CUGAUGAG X 5161 UCUCGGCUC 5998
CGAA
AGCCGAGA ACUGCAAC
1779 GGAGGCAG CUGAUGAG X 5162 CUGCAACUU 5949
CGAA
2 0 AGUUGCAG CUGCCUCC
1775 AGGAGGCA CUGAUGAG X 5163 UGCAACUUC 5950
CGAA
AAGUUGCA UGCCUCCU
1781 AAACCCAG CUGAUGAG X 5164 UUCUGCCUC 5951
CGAA
AGGCAGAA CUGGGUUU
1788 AUCGCUUA CUGAUGAG X 5165 UCCUGGGUU 5952
CGAA
ACCCAGGA UAAGCGAU
1789 AAUCGCUU CUGAUGAG X 5166 CCUGGGUUU 5953
CGAA
AACCCAGG AAGCGAUU
1790 GAAUCGCU CUGAUGAG X 5167 CUGGGUUUA 5959
CGAA
AAACCCAG AGCGAUUC
1797 GCCAGAAG CUGAUGAG X 5168 UAAGCGAUU 5955
CGAA
AUCGCUUA CUUCUGGC
1798 AGCCAGAA CUGAUGAG X 5169 AAGCGAUUC 5956
CGAA
AAUCGCUU UUCUGGCU
CA 02324421 2000-09-26
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239
Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1800 UGAGCCAG CUGAUGAG X 5170 GCGAUUCUU 5957
CGAA
AGAAUCGC CUGGCUCA
1801 CUGAGCCA CUGAUGAG X 5171 CGAUUCUUC 5958
CGAA
AAGAAUCG UGGCUCAG
1807 GGGAGGCU CUGAUGAG X 5172 UUCUGGCUC 5959
CGAA
AGCCAGAA AGCCUCCC
1813 CUACUCGG CUGAUGAG X 5173 CUCAGCCUC 5960
CGAA
AGGCUGAG CCGAGUAG
1820 AUCCCAGC CUGAUGAG X 5174 UCCCGAGUA 5961
CGAA
ACUCGGGA GCUGGGAU
1829 GCGCCUGU GUGAUGAG X 5175 GCUGGGAUU 5962
CGAA
AUCCCAGC ACAGGCGC
1830 GGCGCCUG CUGAUGAG X 5176 CUGGGAUUA 5963
CGAA
AAUCCCAG CAGGCGCC
1856 ACAAAAAU CUGAUGAG X 5177 GGCCGGCUA 5964
CGAA
AGCCGGCC AUUUUUGU
1859 AAUACAAA CUGAUGAG X 5178 CGGCUAAUU 5965
CGAA
AUUAGCCG UUUGUAUU
1860 AAAUACAA CUGAUGAG X 5179 GGCUAAUUU 5966
CGAA
AAUUAGCC UUGUAUUU
1861 AAAAUACA CUGAUGAG X 5180 GCUAAUUUU 5967
CGAA
AAAUUAGC UGUAUUUU
1862 AAAAAUAC CUGAUGAG X 5181 CUAAUUUUU 5968
CGAA
AAAAUUAG GUAUUUUU
1865 ACUAAAAA CUGAUGAG X 5182 AUUUUUGUA 5969
CGAA
ACAAAAAU UUUUUAGU
1867 CUACUAAA CUGAUGAG X 5183 UUUUGUAUU 5970
CGAA
AUACAAAA UUUAGUAG
1868 UCUACUAA CUGAUGAG X 5184 UUUGUAUUU 5971
CGAA
AAUACAAA UUAGUAGA
1869 CUCUACUA CUGAUGAG X 5185 UUGUAUUUU 5972
CGAA
AAAUACAA UAGUAGAG
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate ~ No.
1870 UCUCUACU CUGAUGAG X 5186 UGUAUUUUU 5973
CGAA
AAAAUACA AGUAGAGA
1871 GUCUCUAC CUGAUGAG X 5187 GUAUUUUUA 5979
CGAA
AAAAAUAC GUAGAGAC
1879 CGCGUCUC CUGAUGAG X 5188 UUUUUAGUA 5975
CGAA
ACUAAAAA GAGACGCG
1885 CAUGGUGA CUGAUGAG X 5189 GACGCGGUU 5976
CGAA
ACCGCGUC UCACCAUG
1886 ACAUGGUG CUGAUGAG X 5190 ACGCGGUUU 5977
CGAA
AACCGCGU CACCAUGU
1887 AACAUGGU CUGAUGAG X 5191 CGCGGUUUC 5978
CGAA
AAACCGCG ACCAUGUU
1895 GCCUGGCC CUGAUGAG X 5192 CACCAUGUU 5979
CGAA
ACAUGGUG GGCCAGGC
1908 GAGCUCCA CUGAUGAG X 5193 AGGCUGGUC 5980
CGAA
ACCAGCCU UGGAGCUC
1916 GAGGCCAG CUGAUGAG X 5194 CUGGAGCUC 5981
CGAA
AGCUCCAG CUGGCCUC
1929 GAUCACUU CUGAUGAG X 5195 CCUGGCCUC 5982
CGAA
AGGCCAGG AAGUGAUC
1932 GGUGGGCG CUGAUGAG X 5196 CAAGUGAUC 5983
CGAA
AUCACUUG CGCCCACC
1942 GGGAGGCU CUGAUGAG X 5197 GCCCACCUC 5984
CGAA
AGGUGGGC AGCCUCCC
1948 CACUUUGG CUGAUGAG X 5198 CUCAGCCUC 5985
CGAA
AGGCUGAG CCAAAGUG
1965 CACGCCUG CUGAUGAG X 5199 CUGGGAAUA 5986
CGAA
AUUCCCAG CAGGCGUG
1996 UUAAAAUA CUGAUGAG X 5200 GCCAGGAUU 5987
CGAA
AUCCUGGC UAUUUUAA
1997 UUUAAAAU CUGAUGAG X 5201 CCAGGAUUU 5988
CGAA
AAUCCUGG AUUUUAAA
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
1998 UUUUAAAA CUGAUGAG X 5202 CAGGAUUUA 5989
CGAA
AAAUCCUG UUUUAAAA
2000 CUUUUUAA CUGAUGAG X 5203 GGAUUUAUU 5990
CGAA
AUAAAUCC UUAAAAAG
2001 CCUUUUUA CUGAUGAG X 5204 GAUUUAUUU 5991
CGAA
AAUAAAUC UAAAAAGG
2002 CCCUUUUU CUGAUGAG X 5205 AUUUAUUUU 5992
CGAA
AAAUAAAU AAAAAGGG
2003 UCCCUUUU CUGAUGAG X 5206 UUUAUUUUA 5993
CGAA
AAAAGGGA
2016 UAUCAACA CUGAUGAG X 5207 GGGAAGAUU 5994
CGAA
AUCUUCCC UGUUGAUA
2017 UUAUCAAC CUGAUGAG X 5208 GGAAGAUUU 5995
CGAA
AAUCUUCC GUUGAUAA
2020 AAUUUAUC CUGAUGAG X 5209 AGAUUUGUU 5996
CGAA
ACAAAUCU GAUAAAUU
2024 AGUGAAUU CUGAUGAG X 5210 UUGUUGAUA 5997
CGAA
AUCAACAA AAUUCACU
2028 UUGAAGUG CUGAUGAG X 5211 UGAUAAAUU 5998
CGAA
AUUUAUCA CACUUCAA
2029 UUUGAAGU CUGAUGAG X 5212 GAUAAAUUC 5999
CGAA
AAUUUAUC ACUUCAAA
2033 UAUCUUUG CUGAUGAG X 5213 AAUUCACUU 6000
CGAA
AGUGAAUU CAAAGAUA
2039 UUAUCUUU CUGAUGAG X 5214 AUUCACUUC 6001
CGAA
AAGUGAAU AAAGAUAA
2091 GAAUAGUU CUGAUGAG X 5215 UCAAAGAUA 6002
CGAA
A UCUUUGA A ACUAUUC
2046 UUUCGAA CUGAUGAG X CGAA5216 G AUAAACUA 6003
U
A GUUUAUC U UCGAAAA
2048 AUUUUCG CUGAUGAG X CGAA5217 U AAACUAUU 6009
U
A UAGUUUA C GAAAAUA
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
2049 GUAUUUUC CUGAUGAG X , 5218 AAACUAUUC 6005
CGAA
AAUAGUUU GAAAAUAC
2056 CACUAAAG CUGAUGAG X 5219 UCGAAAAUA 6006
CGAA
AUUUUCGA CUUUAGUG
2059 AAUCACUA CUGAUGAG X 5220 AAAAUACUU 6007
CGAA
AGUAUUUU UAGUGAUU
2060 GAAUCACU CUGAUGAG X 5221 AAAUACUUU 6008
CGAA
AAGUAUUU AGUGAUUC
2061 GGAAUCAC CUGAUGAG X 5222 AAUACUUUA 6009
CGAA
AAAGUAUU GUGAUUCC
2067 UUGACGGG CUGAUGAG X 5223 UUAGUGAUU 6010
CGAA
AUCACUAA CCCGUCAA
2068 CUUGACGG CUGAUGAG X 5224 UAGUGAUUC 6011
CGAA
AAUCACUA CCGUCAAG
2073 AGAGUCUU CUGAUGAG X 5225 AUUCCCGUC 6012
CGAA
ACGGGAAU AAGACUCU
2080 ACACAGAA CUGAUGAG X 5226 UCAAGACUC 6013
CGAA
2 O AGUCUUGA UUCUGUGU
2082 AUACACAG CUGAUGAG X 5227 AAGACUCUU 6014
CGAA
AGAGUCUU CUGUGUAU
2083 CAUACACA CUGAUGAG X 5228 AGACUCUUC 6015
CGAA
AAGAGUCU UGUGUAUG
2 5
2pgg UCUAUACA CUGAUGAG X 5229 UUCUGUGUA 6016
CGAA
ACACAGAA UGUAUAGA
2093 UACGUCUA CUGAUGAG X 5230 GUGUAUGUA 6017
CGAA
ACAUACAC UAGACGUA
2095 UAUACGUC CUGAUGAG X 5231 GUAUGUAUA 6018
CGAA
30
AUACAUAC GACGUAUA
2101 AUGAGUUA CUGAUGAG X 5232 AUAGACGUA 6019
CGAA
ACGUCUAU UAACUCAU
2103 GAAUGAGU CUGAUGAG X 5233 AGACGUAUA 6020
CGAA
AUACGUCU ACUCAUUC
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
2107 UCCAGAAU CUGAUGAG X 5234 GUAUAACUC 6021
CGAA
AGUUAUAC AUUCUGGA
2110 CUGUCCAG CUGAUGAG X 5235 UAACUCAUU 6022
CGAA
AUGAGUUA CUGGACAG
2111 CCUGUCCA CUGAUGAG X 5236 AACUCAUUC 6023
CGAA
AAUGAGUU UGGACAGG
2128 AAAAAAGA CUGAUGAG X 5237 GCAAGGAUA 6024
CGAA
AUCCUUGC UCUUUUUU
2130 CAAAAAAA CUGAUGAG X 5238 AAGGAUAUC 6025
CGAA
AUAUCCUU UUUUUUUG
2132 AACAAAAA CUGAUGAG X 5239 GGAUAUCUU 6026
CGAA
AGAUAUCC UUUUUGUU
2133 AAACAAAA CUGAUGAG X 5240 GAUAUCUUU 6027
CGAA
AAGAUAUC UUUUGUUU
2134 CAAACAAA CUGAUGAG X 5241 AUAUGUUUU 6028
CGAA
AAAGAUAU UUUGUUUG
2135 ACAAACAA CUGAUGAG X 5242 UAUCUUUUU 6029
CGAA
AAAAGAUA UUGUUUGU
2136 AACAAACA CUGAUGAG X 5243 AUCUUUUUU 6030
CGAA
AAAAAGAU UGUUUGUU
2137 AAACAAAC CUGAUGAG X 5244 UCUUUUUUU 6031
CGAA
AAAP~APrGA GUUUGUUU
2 5 2190 AACAAACA CUGAUGAG X 5295 UUUUUUGUU 6032
CGAA
ACAAAAAA UGUUUGUU
2141 AAACAAAC CUGAUGAG X 5246 UUUUUGUUU 6033
CGAA
AACAAAAA GUUUGUUU
2144 AACAAACA CUGAUGAG X 5247 UUGUUUGUU 6034
CGAA
ACAAACAA UGUUUGUU
2145 AAACAAAC CUGAUGAG X 5248 UGUUUGUUU 6035
CGAA
AACAAACA GUUUGUUU
2148 UCAAAACA CUGAUGAG X 5249 UUGUUUGUU 6036
CGAA
ACAAACAA UGUUUUGA
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
2199 CUCAAAAC CUGAUGAG X 5250 UGUUUGUUU 6037
CGAA
AACAAACA GUUUUGAG
2152 CAUCUCAA CUGAUGAG X 5251 UUGUUUGUU 6038
CGAA
ACAAACAA UUGAGAUG
2153 CCAUCUCA CUGAUGAG X 5252 UGUUUGUUU 6039
CGAA
AACAAACA UGAGAUGG
2154 UCCAUCUC CUGAUGAG X 5253 GUUUGUUUU 6040
CGAA
AAACAAAC GAGAUGGA
2165 GACAGCGA CUGAUGAG X 5254 GAUGGACUC 6041
CGAA
AGUCCAUC UCGCUGUC
2167 GCGACAGC CUGAUGAG X 5255 UGGACUCUC 6042
CGAA
AGAGUCCA GCUGUCGC
2173 AGCCUGGC CUGAUGAG X 5256 CUCGCUGUC 6043
CGAA
ACAGCGAG GCCAGGCU
2182 CUGCACUC CUGAUGAG X 5257 GCCAGGCUA 6049
CGAA
AGCCUGGC GAGUGCAG
2200 UGAGCUGA CUGAUGAG X 5258 GGCGCGAUU 6045
CGAA
AUCGCGCC UCAGCUCA
2201 GUGAGCUG CUGAUGAG X 5259 GCGCGAUUU 6096
CGAA
AAUCGCGC CAGCUCAC
2202 AGUGAGCU CUGAUGAG X 5260 CGCGAUUUC 6047
CGAA
AAAUCGCG. AGCUCACU
2207 GUUGCAGU CUGAUGAG X 5261 UUUCAGCUC 6048
CGAA
AGCUGAAA ACUGCAAC
2218 GGGAAGCG CUGAUGAG X 5262 UGCAACCUC 6099
CGAA
AGGUUGCA CGCUUCCC
2223 AACCCGGG CUGAUGAG X 5263 CCUCCGCUU 6050
CGAA
AGCGGAGG CCCGGGUU
2224 GAACCCGG CUGAUGAG X 5264 CUCCGCUUC 6051
CGAA
AAGCGGAG CCGGGUUC
2231 AUCGCUUG CUGAUGAG X 5265 UCCCGGGUU 6052
CGAA
ACCCGGGA CAAGCGAU
CA 02324421 2000-09-26
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
2232 AAUCGCUU CUGAUGAG X 5266 CCCGGGUUC 6053
CGAA
AACCCGGG AAGCGAUU
2240 GGCAGGAG CUGAUGAG X 5267 CAAGCGAUU 6054
CGAA
AUCGCUUG CUCCUGCC
2241 AGGCAGGA CUGAUGAG X 5268 AAGCGAUUC 6055
CGAA
AAUCGCUU UCCUGCCU
2243 UGAGGCAG CUGAUGAG X 5269 GCGAUUCUC 6056
CGAA
AGAAUCGC CUGCCUCA
2250 GGGAGGCU CUGAUGAG X 5270 UCCUGCCUC 6057
CGAA
AGGCAGGA AGCCUCCC
2256 CUACUCGG CUGAUGAG X 5271 CUCAGCCUC 6058
CGAA
AGGCUGAG CCGAGUAG
2263 AUCCCAGC CUGAUGAG X 5272 UCCCGAGUA 6059
CGAA
ACUCGGGA GCUGGGAU
22?2 GUGCCUGU CUGAUGAG X 5273 GCUGGGAUU 6060
CGAA
AUCCCAGC ACAGGCAC
2273 CGUGCCUG CUGAUGAG X 5279 CUGGGAUUA 6061
CGAA
2 O AAUCCCAG CAGGCACG
2296 AAAAUUAG CUGAUGAG X 5275 CACGCCCUA 6062
CGAA
AGGGCGUG CUAAUUUU
2299 UCAAAAAU CUGAUGAG X 5276 GCCCUACUA 6063
CGAA
AGUAGGGC AUUUUUGA
2302 AAAUCAAA CUGAUGAG X 5277 CUACUAAUU 6069
CGAA
AUUAGUAG UUUGAUUU
2303 AAAAUCAA CUGAUGAG X 5278 UACUAAUUU 6065
CGAA
AAUUAGUA UUGAUUUU
2304 AAAAAUCA CUGAUGAG X 5279 ACUAAUUUU 6066
CGAA
~UUAGU UGAUUUUU
2305 UAAAAAUC CUGAUGAG X 5280 CUAAUUUUU 606?
CGAA
AAAAUUAG GAUUUUUA
2309 CUACUAAA CUGAUGAG X 5281 UUUUUGAUU 6068
CGAA
AUCAAAAA G ~
UUUAGUA
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Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
2310 UCUACUAA CUGAUGAG X 5282 UUUUGAUUU 6069
CGAA
AAUCAAAA UUAGUAGA
2311 CUCUACUA CUGAUGAG X 5283 UUUGAUUUU 6070
CGAA
AAAUCAAA UAGUAGAG
2312 UCUCUACU CUGAUGAG X 5284 UUGAUUUUU 6071
CGAA
AAAAUCAA AGUAGAGA
2313 GUCUCUAC CUGAUGAG X 5285 UGAUUUUUA 6072
CGAA
AAAAAUCA GUAGAGAC
2316 CCCGUCUC CUGAUGAG X 5286 UUUUUAGUA 6073
CGAA
ACUAAAAA GAGACGGG
2327 CAUGGGGA CUGAUGAG X 5287 GACGGGAUU 6074
CGAA
AUCCCGUC UCCCCAUG
2328 ACAUGGGG CUGAUGAG X 5288 ACGGGAUUU 6075
CGAA
AAUCCCGU CCCCAUGU
2329 AACAUGGG CUGAUGAG X 5289 CGGGAUUUC 6076
CGAA
AAAUCCCG CCCAUGUU
2337 UCCUGGCC CUGAUGAG X 5290 CCCCAUGUU 6077
CGAA
ACAUGGGG GGCCAGGA
2350 GAGAUCGA CUGAUGAG X 5291 AGGAUGAUC 6078
CGAA
AUCAUCCU UCGAUCUC
2352 AAGAGAUC CUGAUGAG X 5292 GAUGAUCUC 6079
CGAA
AGAUCAUC GAUCUCUU
2356 GGUCAAGA CUGAUGAG X 5293 AUCUCGAUC 6080
CGAA
AUCGAGAU UCUUGACC
2358 GGGGUCAA CUGAUGAG X 5299 CUCGAUCUC 6081
CGAA
AGAUCGAG UUGACCCC
2360 ACGGGGUC CUGAUGAG X 5295 CGAUCUCUU 6082
CGAA
AGAGAUCG GACCCCGU
2372 GGCAGGCU CUGAUGAG X 5296 CCCGUGAUC 6083
CGAA
AUCACGGG AGCCUGCC
2382 GGGAGGCC CUGAUGAG X 5297 GCCUGCCUU 6084
CGAA
AGGCAGGC GGCCUCCC
CA 02324421 2000-09-26
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247
Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
2388 CACUUUGG CUGAUGAG X 5298 CUUGGCCUC 6085
CGAA
AGGCCAAG CCAAAGUG
2904 ACGCCUGU CUGAUGAG X 5299 GCUGGGAUU 6086
CGAA
AUCCCAGC ACAGGCGU
2405 CACGCCUG CUGAUGAG X 5300 CUGGGAUUA 6087
CGAA
AAUCCCAG CAGGCGUG
2437 CUUCAAGA CUGAUGAG X 5301 CCAAGGGUA 6088
CGAA
ACCCUUGG UCUUGAAG
2439 UCCUUCAA CUGAUGAG X 5302 AAGGGUAUC 6089
CGAA
AUACCCUU UUGAAGGA
2441 CCUCCUUC CUGAUGAG X 5303 GGGUAUCUU 6090
CGAA
AGAUACCC GAAGGAGG
2453 UCAACUGU CUGAUGAG X 5304 GGAGGGAUU 6091
CGAA
AUCCCUCC ACAGUUGA
2454 AUCAACUG CUGAUGAG X 5305 GAGGGAUUA 6092
CGAA
AAUCCCUC CAGUUGAU
2459 UACAUAUC CUGAUGAG X 5306 AUUACAGUU 6093
CGAA
2 O ACUGUAAU GAUAUGUA
2463 CCUCUACA CUGAUGAG X 5307 CAGUUGAUA 6094
CGAA
AUCAACUG UGUAGAGG
2467 UAUUCCUC CUGAUGAG X 5308 UGAUAUGUA 6095
CGAA
ACAUAUCA GAGGAAUA
2 5 2475 CACUGCAA CUGAUGAG X 5309 AGAGGAAUA 6096
CGAA
AUUCCUCU UUGCAGUG
2977 ACCACUGC CUGAUGAG X 5310 AGGAAUAUU 6097
CGAA
AUAUUCCU GCAGUGGU
2486 GCAGCAAU CUGAUGAG X 5311 GCAGUGGUU 6098
CGAA
30
ACCACUGC AUUGCUGC
2987 UGCAGCAA CUGAUGAG X 5312 CAGUGGUUA 6099
CGAA
AACCACUG UUGCUGCA
2989 AAUGCAGC CUGAUGAG X 5313 GUGGUUAUU 6100
CGAA
AUAACCAC GCUGCAUU
CA 02324421 2000-09-26
WO 99/50403 PCT/US99/0650'1
248
Posi- Seq. I.D. Seq. I.D.
tion RZ No. Substrate No.
2497 ACAUAGGA CUGAUGAG X 5314 UGCUGCAUU 6101
CGAA
AUGCAGCA UCCUAUGU
2498 CACAUAGG CUGAUGAG X 5315 GCUGCAUUU 6102
CGAA
AAUGCAGC CCUAUGUG
2499 UCACAUAG CUGAUGAG X 5316 CUGCAUUUC 6103
CGAA
AAAUGCAG CUAUGUGA
2502 CAGUCACA CUGAUGAG X 5317 CAUUUCCUA 6104
CGAA
AGGAAAUG UGUGACUG
2516 AUCUGUUU CUGAUGAG X 5318 CUGGGACUA 6105
CGAA
AGUCCCAG AAACAGAU
2525 UAUCAGCU CUGAUGAG X 5319 AAACAGAUC 6106
CGAA
AUCUGUUU AGCUGAUA
2533 GCUAACAC CUGAUGAG X 5320 CAGCUGAUA 6107
CGAA
AUCAGCUG GUGUUAGC
2538 UGCACGCU CUGAUGAG X 5321 GAUAGUGUU 6108
CGAA
ACACUAUC AGCGUGCA
2539 CUGCACGC CUGAUGAG X 5322 AUAGUGUUA 6109
CGAA
2 O AACACUAU GCGUGCAG
2556 AGUCAUCA CUGAUGAG X 5323 UGAGCAGUC 6110
CGAA
ACUGCUCA UGAUGACU
2565 CUGUGUCA CUGAUGAG X 5329 UGAUGACUA 6111
CGAA
AGUCAUCA UGACACAG
2578 GAGAUUCU CUGAUGAG X 5325 ACAGAAAUA 6112
CGAA
AUUUCUGU AGAAUCUC
2584 AUGCUGGA CUGAUGAG X 5326 AUAAGAAUC 6113
CGAA
AUUCUUAU UCCAGCAU
2586 GAAUGCUG CUGAUGAG X 5327 AAGAAUCUC 6114
CGAA
AGAUUCUU CAGCAUUC
2593 CAGGGCAG CUGAUGAG X 5328 UCCAGCAUU 6115
CGAA
AUGCUGGA CUGCCCUG
2594 CCAGGGCA CUGAUGAG X 5329 CCAGCAUUC 6116
CGAA
AAUGCUGG UGCCCUGG
. CA 02324421 2000-09-26
DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDS OU CE BREVET
COMPREND PLUS D'UN TOME.
CEC! EST LE TOME ~ DE -
NOTE: Pour les tomes additionels, veuillez contacter le Bureau canadien des
brevets -
JUMBO APPL1CATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE
THAN ONE VOLUME
THIS IS VOLUME ~ OF tT
NOTE:.For additional voiumes~please contact'the Canadian Patent Ofif~ce
