AU3364799A - Method and reagents for the treatment of diseases or conditions related to molecules involved in angiogenic responses - Google Patents

Description

WO 99/50403 PCTIUS99/06507 1 DESCRIPTION Method And Reagents For The Treatment Of Diseases Or Conditions Related To Molecules Involved In Angiogenic Responses 5 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. 10 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 15 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 20 form a vascular plexus which supplies nutrients to the embryo (Merenmies et al., 1997, Gell 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 25 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 30 such as the brain and kidney are vascularized through the angiogenic process (Dumont et al., 1995, Developmental Dynamics 203, 80-92).

WO 99/50403 PCT/US99/06507 2 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. 5 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, 10 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 15 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 20 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 25 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 30 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 35 increased angiogenesis including: WO 99/50403 PCTIUS99/06507 3 1) ryl Hydrocarbon Nuclear Transporter (ARNT): ARNT (also known as HIF-1P) forms heterodimers with several factors including HIF-a (Maxwell et al., 1997, Proc. Natl. Acad. Sci. USA 94, 8104-8109). When HIF-a and ARNT complex 5 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 10 knockout mice, these embryos show defective angiogenesis of the yolk sac (Maltepe et al., 1997, Nature 386, 403 407) . Hepatoma cells containing an ARNT mutation that is functionally deficient in dimerizing with HIF-lcshows 15 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, 20 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 25 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 9p2l (Dumont et al., 1994, Genes & Development 8, 1897-1909) . Tie-2 homozygous mutant 30 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 35 indistinguishable from small vessels and no capillary WO 99/50403 PCT/US99/06507 4 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-i mutant 5 indicates separate roles for the two RTK's in angiogenesis. Ligands to Tie-2 have been discovered and named angiopoietin 1 and 2 (angi and 2) (Davis, S. et al., 1993, Cell 87, 1161; Maisonpierre, P.C. et al.,1997, Science, 10 277, 55-60). Both factors consist of an NH 2 -terminal coiled-coil domain as well as a COOH-terminal fibrinogen like domain. Angl binds to Tie-2/Tek but not Tie-i and stimulates angiogenesis through autophosphorylation. Ang2 is a 496 amino acid polypeptide whose human and mouse 15 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 20 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 ap non-covalently bound heterodimers on cell surfaces (Varner, 1997, Regulation of Angiogenesis, ed I.D Goldberg & E.M. Rosen, 25 361-390; Brooks, 1996, Eur J Cancer 14, 2423-2429). Each combination of integrin subunits is thought to have angiogenic capabilities, for example a 6 si has been implicated in capillary tube formation Additionally, distinct integrins allow for the attachment to many 30 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, 35 calcium concentration, inositol lipid synthesis, tyrosine WO 99/50403 PCT/US99/06507 5 phosphorylation of a focal contact associated tyrosine kinase, and activation of p34/cdc2 and cyclin A (Varner & Cheresh, 1996, Curr Op in Cell Biol 8,724-730). cv3 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,3 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 10 of the ECM components (Varner, 1997, supra) . When vascular endothelial cells are in their quiescent state very little acvP 3 is expressed, but is highly upregulated in several pathological conditions including neoplasms. Antagonists to av33 can inhibit angiogenesis in the chick 15 chorioallentoic membrane (CAM) model and in SCID mice and even reduce the tumor volume. When antibodies are administered for Ap 3 , apoptosis is observed in the proliferating vascular vessels. This has led to suggestions that avP3 provides a survival signal for 20 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 25 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 al. 1996.J. Cell Physiol. 169, 522-531; 30 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 & 35 PD-ECGFr): (Furukawa, T. et al., 1992, Nature 356, 668; WO 99/50403 PCT/US99/06507 6 Moghaddam, A. et al., 1995, Proc. Natl. Acad. Sci.; Clark, R.A.F. et al. ,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; 5 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 4 (4) , 247-255; Sukurai (unpublished) 10 (Genbank accession No. AB009356);Transforming growth factor receptor: (Miyazono, K.,1996, Nippon Yakurigaku Zasshu 107, 133-140; Mahooti-Brooks. et al.,1996, J. Clin. Invest. 97, 1436-1446; Lopez-Casillas et al., 1991, Cell 67 (4), 797-805; Lopez-Casillas et al., 1991, Cell 67 (4), 15 785-795 (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. Biol 234, 41-53; Shapiro & Vallee,1987, PNAS 84, 2238-2241; Shapiro et al.,1986, Biochemistry 25, 20 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 al.,1995,. J. Inflamm 47, 1-7; Loetscher et 25 al., 1990, Cell 61, 351-359; Himmler et al., 1990, DNA Cell Biol. 9, 705-715 (Genbank Accession No. M63121 M75861); Endothelial cell stimulating angiogenesis factor (ESAF): (Brown & Weiss,1988,. Ann. Rheum. Dis., 47, 881 885) ; Interleukin-8 (IL-8) : (Elner et al. , 1991, , Am 30 J. Pathol. 139, 977-988; Strieter et al.,1992, Am. J. Pathol. 141, 1279-1284; Mukaida et al., 1989, J. Immunol. 143 (4), 1366-1371(Genbank Accession No. M28130)); Angiopoietin 1: (Davis, S. et al.,1996, Cell 87, 1161; Iwama, A. et al.,1993, Biochem Biophys. Res. Commun. 195, 35 301; Dumont, D.J. et al.,1995, Genes Dev 8, 1897; Sato, WO 99/50403 PCT/US99/06507 7 T.N. et al.,1995, Nature 376, 70; Suri, C. et al., 1996) Cell 87, 1171(Genbank Accession No. U83508)); Angiopoietin 2: (Maisonpierre, et al.,1997, Science, 277, 55-60; Hanahan, 1997, Science 277, 48-50; Genbank Accession No. 5 AF004327 (unpublished));Insulin-like growth factor (IGF 1): (Warren, R.S. et al.,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, 10 507-514 (Genbank Accession: X57025); Insulin-like growth factor receptor (IGF-lr) : (Ullrich et al., 1986, EMBO J. 5, 2503-2512 (Genbank Accession No. X04434 M24599); B61: (Pandey, A. et al., 1995, Science 268, 567-569; Holzman et al., 1990, Mol. Cell. Biol. 10, 5830-5838 (Genbank 15 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) 25 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. 30 et al.,1991, Cell Signalling 3, 501-513; Genbank accession No. Z29090; Genbank accession No. Z46973) c. Ras GTPase activating protein (GAP): (Trahey, M. et al.,1987, Science 238, 542-545; Guo, D. et al., 1995, J. Biol. Chem 270, 6729-6733; Trahey et al., 1988, Science 35 242, 1697-1700 (Genbank accession No. M23612)) WO 99/50403 PCT/US99/06507 8 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., 5 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, 10 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 15 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. 20 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. 25 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 03, integrin subunit x6, and aryl hydrocarbon nuclear transporter (ARNT). 30 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 WO 99/50403 PCT/US99/06507 9 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 5 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 10 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 15 8); Angiopoietin 1 and 2; TIE-1; insulin-like growth factor (IGF-1); insulin-like growth factor receptor (IGF 1r); 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); 20 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, 25 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 30 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 35 complementarity functions to allow sufficient WO 99/50403 PCT/US99/06507 10 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 15 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 20 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 25 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 30 portion of its substrate. Generally, such complementarity is 100%, but can be less if desired. For example, as few as 10 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 35 ribozyme and target RNA together through complementary WO 99/50403 PCTIUS99/06507 11 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 arm(s) are preferably greater than or equal to 5 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 10 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 15 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 20 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 25 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 30 d virus motif is described by Perrotta and Been, 1992 Biochemistry 31, 16; of the RNaseP motif by Guerrier Takada et al., 1983 Cell 35, 849; Forster and Altman, 1990, Science 249, 783; Li and Altman, 1996, Nucleic Acids Res. 24, 835; Neurospora VS RNA ribozyme motif is 35 described by Collins (Saville and Collins, 1990 Cell 61, WO 99/50403 PCTIUS99/06507 12 685-696; 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, 5 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 10 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 15 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. 20 Patent No. 4,987,071). By "equivalent" RNA to Tie-2, integrin subunit $3, integrin subunit ax6, or ARNT is meant to include those naturally occurring RNA molecules having homology (partial or complete) to Tie-2, integrin subunit P3, integrin 25 subunit (x6, or ARNT or encoding for proteins with similar function as Tie-2, integrin subunit P3, 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 30 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.

WO 99/50403 PCTIUS99/06507 13 By "complementarity" is meant a nucleic acid molecules that can form hydrogen bond(s) with another nucleic acid sequence by either traditional Watson-Crick or other non-traditional types (for example, Hoogsteen 5 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 10 preferably targeted to a highly conserved sequence region of a target RNAs encoding Tie-2, integrin subunit P3, 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 15 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 20 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 25 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 30 syndrome, Osler-Weber-Rendu syndrome and any other diseases or conditions that are related to the levels of Tie-2, integrin subunit P3, integrin subunit ax6, or ARNT activity in a cell or tissue. By "related" is meant that the inhibition of Tie-2, 35 integrin subunit P3, integrin subunit ax6, and/or ARNT RNAs WO 99/50403 PCT/US99/06507 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 ribozymes have binding 5 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 10 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. 15 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 20 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 25 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, 30 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 WO 99/50403 PCT/US99/06507 15 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 P3, 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 $3, 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 20 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 25 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. Delivery of ribozyme expressing vectors could be systemic, such as by intravenous or intramuscular 30 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 35 another aspect of the invention, ribozymes that cleave WO 99/50403 PCTIUS99/06507 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 5 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. 10 "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 15 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, 20 integrin subunit P3, 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 25 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 30 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.1-393, 787-848, 911-1611, 2313-2380, 2449-3587, WO 99/50403 PCTIUS99/06507 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 5 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 10 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 15 (Cech et al., 1994, Nature Struc. Bio., 1, 273). RNase 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 20 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. WO 96/19577). HDV 25 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, 30 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 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 1 base). Helix 1, 4 or 5 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 10 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 15 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., 20 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 2 bases. The connecting loop can also be replaced with a non-nucleotide linker molecule. H refers to bases A, U, 25 or C. Y refers to pyrimidine bases. " " refers to a covalent bond. (Burke et al., 1996, Nucleic Acids & Mol. Biol., 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 30 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, 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 5 641; Joyce, 1992, Scientific American 267, 90-97; Breaker et al., 1994, TIBTECH 12, 268; Bartel et al.,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. 10 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 15 reactions including the hydrolysis of phosphodiester bonds in trans (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 20 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 25 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 30 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 35 lower. This advantage reflects the ability of the WO 99/50403 PCT/US99/06507 20 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, 334 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, 25 285-294; 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 30 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 $3, integrin subunit a6, and aryl hydrocarbon nuclear transporter (ARNT) mRNAs represent a 35 novel therapeutic approach to treat cancer, macular WO 99/50403 PCTIUS99/06507 21 degeneration, diabetic retinopathy, inflammation, psoriasis and other diseases. Applicant indicates that ribozymes are able to inhibit the activity of Tie-2; integrin subunit P3; integrin subunit ax6; and aryl 5 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 10 P3, 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 15 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. 5,525,468 and hereby incorporated by reference herein in totality. Rather than repeat the guidance provided in those 20 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 25 optimized and delivered as described therein. The sequence of human Tie-2, integrin subunit 13, integrin subunit c6, and aryl hydrocarbon nuclear transporter (ARNT) mRNAs were screened for optimal ribozyme target sites using a computer folding algorithm. 30 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 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 5 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 10 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 15 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 20 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 25 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; 30 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- WO 99/50403 PCTIUS99/06507 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 5 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 10 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 15 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 20 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 pmol scale protocol with a 5 min coupling 25 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 pL of 0.1 M = 16.3 pmol) of phosphoramidite and a 24 30 fold excess of S-ethyl tetrazole (238 pL of 0.25 M = 59.5 pmol) 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 35 97.5-99%. Other oligonucleotide synthesis reagents for the 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); 5 oxidation solution was 16.9 mM 12, 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 10 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) 15 at 65 0C for 10 min. After cooling to -20 0C, the supernatant was removed from the polymer support. The support was washed three times with 1.0 mL of EtOH:MeCN:H 2 0/3:1:1, vortexed and the supernatant was then added to the first supernatant. The combined supernatants, 20 containing the oligoribonucleotide, were dried to a white powder. The base-deprotected oligoribonucleotide was resuspended in anhydrous TEA-HF/NMP solution (250 pL of a solution of 1.5mL N-methylpyrrolidinone, 750 pL TEA and 25 1.0 mL TEAe3HF to provide a 1.4M HF concentration) and heated to 650C 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 30 oligomer, the TEAB 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.

WO 99/50403 PCTIUS99/06507 25 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 30 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 35 paired stem structure can form. Similarly, stem-loop IV WO 99/50403 PCT/US99/06507 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 5 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. 10 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, 15 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 20 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 25 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 30 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 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 5 catalytic activity by modification with nuclease resistant groups, for example, 2'-amino, 2'-C-allyl, 2'-flouro, 2' 0-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., 10 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 al. Nature 1990, 344, 565-568; Pieken et al. Science 1991, 253, 314 15 317; Usman and Cedergren, Trends in Biochem. Sci. 1992, 17, 334-339; Usman et al. 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 20 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 25 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. 30 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 35 reduced 10 fold (Burgin et al., 1996, Biochemistry, 35, WO 99/50403 PCTIUS99/06507 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 5 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 10 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 15 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 20 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 25 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 30 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 35 their catalytic activity include, inosine, purine, WO 99/50403 PCT/US99/06507 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 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' 10 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 15 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 20 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 25 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 30 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 WO 99/50403 PCT/US99/06507 30 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, 35 hydrobromic, acetic acid, and benzene sulfonic acid.

WO 99/50403 PCT/US99/06507 31 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, 5 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, 10 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. 15 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, 20 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 25 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 30 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 WO 99/50403 PCTIUS99/06507 32 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 5 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 10 mononuclear phagocytic system (MPS or RES), thereby enabling longer blood circulation times and enhanced tissue exposure for the encapsulated drug (Lasic et al. Chem. Rev. 1995, 95, 2601-2627; Ishiwataet al., Chem. Pharm. Bull. 1995, 43, 1005-1011) . Such liposomes have 15 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 al.,1995, Biochim. Biophys. Acta, 1238, 86-90). The long-circulating liposomes enhance the pharmacokinetics 20 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., 25 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 30 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 35 prepared for storage or administration which include a WO 99/50403 PCT/US99/06507 33 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, 5 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 1449. These include sodium benzoate, 10 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 15 (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 20 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 25 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. 30 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. 35 USA 89, 10802-6; Chen et al., 1992 Nucleic Acids Res., WO 99/50403 PCT/US99/06507 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, 4, 45; all of the references are hereby incorporated in their totality by reference 5 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, 10 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 15 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 20 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 25 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 30 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 35 ribozyme expressing vectors could be systemic, such as by WO 99/50403 PCTIUS99/06507 35 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 WO 99/50403 PCT/US99/06507 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 5 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 10 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 15 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 20 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 25 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 30 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, 1996, supra).

WO 99/50403 PCT/US99/06507 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 5 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 molecule; and wherein said gene is operably linked to said 10 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 region; b) a transcription termination region; c) an open 15 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 20 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 25 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 30 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 frame; and 35 wherein said gene is operably linked to said initiation WO 99/50403 PCT/US99/06507 38 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 5 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 10 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 15 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. 20 Thus, inhibition requires the catalytic activity of the ribozymes. Example 1: Identification of Potential Ribozyme Cleavage Sites in TIE-2 The sequence of human Tie-2 was screened for 25 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 30 VI.

WO 99/50403 PCT/US99/06507 39 Example 2: Selection of Ribozyme Cleavage Sites in Human TIE-2 RNA To test whether the sites predicted by the computer based RNA folding algorithm corresponded to accessible 5 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 10 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 15 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 20 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 25 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 30 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 WO 99/50403 PCT/US99/06507 40 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'-0-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- 3 2 p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA WO 99/50403 PCT/US99/06507 41 without further purification. Alternately, substrates are 5'- 3 2 P-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 5 HCl, pH 7.5 at 370C, 10 mM MgCl 2 ) 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, 0 assays are carried out for 1 hour at 37 C using a final 10 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 15 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 20 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 25 Biophysica Acta 1032, 89-118) . Elevated levels of a number of these angiogenic factors including Tie-2; integrin subunit P3; integrin subunit a6; and aryl hydrocarbon nuclear transporter have been reported in a number of cancers. Thus, inhibition of expression of 30 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 WO 99/50403 PCTIUS99/06507 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 5 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 10 (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 15 vascular endothelial growth factor (VEGF) have been reported in vascularized and edema-associated brain tumors (Berkman 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 20 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 25 vascularization induced by human glioblastoma cells in nude mice (Millauer et al., 1994, Nature 367, 576). 2) Ocular diseases: Neovascularization has been shown to cause or exacerbate ocular diseases including but not limited to, macular degeneration, neovascular 30 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 WO 99/50403 PCT/US99/06507 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 5 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, 10 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., 15 1992, Angiogenesis: Key principles-Science-Technology Medicine, ed R. Steiner) Detmar et al., 1994 J. Exp. Med. 180, 1141 reported that VEGF and its receptors were over-expressed in psoriatic skin and psoriatic dermal microvessels, suggesting that VEGF plays a significant 20 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., 25 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 30 role for VEGF in rheumatoid arthritis. Other angiogenic factors including those of the present invention may also be involved in arthritis.

WO 99/50403 PCT/US99/06507 44 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 5 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 10 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 15 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). 20 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 25 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 30 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 35 Diabetologia 36: 282-291; Pandey et al. 1995 supra; WO 99/50403 PCT/US99/06507 45 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 (O'Reilly et al., 1994 Cell 79: 315-328; Senger et al., 1993 Cancer and Metas. Rev. 12: 303-324; 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 WO 99/50403 PCT/US99/06507 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 5 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, 10 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 15 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 20 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 25 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 30 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 35 models which involve indirect correltations with WO 99/50403 PCT/US99/06507 47 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 5 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. 10 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 15 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 20 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 25 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 30 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.

WO 99/50403 PCT/US99/06507 48 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 5 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 10 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 15 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. 20 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 25 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). 30 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 WO 99/50403 PCT/US99/06507 49 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 5 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; 10 integrin subunit $3; 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 15 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 20 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 25 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 30 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 P3; integrin subunit x6; and/or aryl hydrocarbon nuclear transporter related condition. Such WO 99/50403 PCT/US99/06507 50 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 P3; 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.

WO 99/50403 PCT/US99/06507 51 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 5 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 10 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.

WO 99/50403 PCT/US99/06507 52 TABLE I Characteristics of naturally occurring ribozymes Group I Introns - Size: -150 to >1000 nucleotides. 5 - Requires a U in the target sequence immediately 5' of the cleavage site. 0 Binds 4-6 nucleotides at the 5'-side of the cleavage site. e Reaction mechanism: attack by the 3'-OH of 10 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. 15 - 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 20 through phylogenetic comparisons, mutagenesis, and biochemical studies [1,2] . 0 Complete kinetic framework established for one ribozyme ( , 4,5,6] . 1 Michel, Francois; Westhof, Eric. Slippery substrates. Nat. Struct. Biol. (1994), 1(1), 5-7. 2 Lisacek, Frederique; Diaz, Yolande; Michel, Francois. Automatic identification of group I intron cores in genomic DNA sequences. J. Mol. Biol. (1994), 235(4), 1206-17. 2 Herschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the WO 99/50403 PCTIUS99/06507 53 Studies of ribozyme folding and substrate docking underway [ 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. 9 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.

WO 99/50403 PCT/US99/06507 54 - Chemical modification investigation of important residues well established [1,1] . * The small (4-6 nt) binding site may make this ribozyme too non-specific for targeted RNA cleavage, 5 however, the Tetrahymena group I intron has been used to repair a "defective" P-galactosidase message by the ligation of new P-galactosidase sequences onto the defective message [ . RNAse P RNA (Ml RNA) 10 - Size: -290 to 400 nucleotides. e RNA portion of a ubiquitous ribonucleoprotein enzyme. e Cleaves tRNA precursors to form mature tRNA [12]. - Reaction mechanism: possible attack by M -OH to 15 generate cleavage products with 3'-OH and 5'-phosphate. 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. i 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. Sullenger, Bruce A.; Cech, Thomas R.. Ribozyme-mediated repair of defective mRNA by targeted trans-splicing. Nature (London) (1994), 371(6498), 619-22. 13 Robertson, H.D.; Altman, S.; Smith, J.D. J. Biol. Chem., 247, 5243-5251 (1972).

WO 99/50403 PCT/US99/06507 55 - 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 Important phosphate and 2' OH contacts recently identified [16, 1] 10 Group II Introns - Size: >1000 nucleotides. Trans cleavage of target RNAs recently demonstrated [8,12 . Forster, Anthony C.; Altman, Sidney. External guide sequences for an RNA enzyme. Science (Washington, D. C., 1883-) (1990), 249(4970), 783-6. Yuan, Y.; Hwang, E. S.; Altman, S. Targeted cleavage of mRNA by human RNase P. Proc. Natl. Acad. Sci. USA (1992) 89, 8006-10. Harris, Michael E.; Pace, Norman R.. Identification of phosphates involved in catalysis by the ribozyme RNase P RNA. RNA (1995), 1(2), 210-18. 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 14. 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.

WO 99/50403 PCT/US99/06507 56 - 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. 5 Only natural ribozyme with demonstrated participation in DNA cleavage [-,-] in addition to RNA cleavage and ligation. - Major structural features largely established through phylogenetic comparisons [2] . 10 - Important 2' OH contacts beginning to be identified [23] i19 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), 34(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. 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. Michel, Francois; Ferat, Jean Luc. Structure and activities of group II introns. Annu. Rev. Biochem. (1995), 64, 435-61. 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.

WO 99/50403 PCT/US99/06507 57 * Kinetic framework under development [i] Neurospora VS RNA Size: -144 nucleotides. Trans cleavage of hairpin target RNAs recently 5 demonstrated [2] . - Sequence requirements not fully determined. e Reaction mechanism: attack by 2'-OH 5' to the scissile bond to generate cleavage products with 2',3' cyclic phosphate and 5'-OH ends. 10 Binding sites and structural requirements not fully determined. * Only 1 known member of this class. Found in Neurospora VS RNA. Hammerhead Ribozyme 15 (see text for references) - Size: ~13 to 40 nucleotides. - Requires the target sequence UH immediately 5' of the cleavage site. - Binds a variable number nucleotides on both 20 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. 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), 31-49. 25 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.

WO 99/50403 PCT/US99/06507 58 - 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, 5 including 2 crystal structures [E,] - Minimal ligation activity demonstrated (for engineering through in vitro selection) [ -8] - Complete kinetic framework established for two or more ribozymes [9] . 10 - Chemical modification investigation of important residues well established [3]. Hairpin Ribozyme - Size: -50 nucleotides. 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. McKay, Structure and function of the hammerhead ribozyme: an unfinished story. RNA, (1996), 2, 395-403. Long, D., Uhlenbeck, 0., Hertel, K. Ligation with hammerhead ribozymes. US Patent No. 5,633,133. 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. Beigelman, L., et al., Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270, 25702-25708.

WO 99/50403 PCT/US99/06507 59 - 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 5 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 10 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 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. 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. Berzal-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. 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.

WO 99/50403 PCT/US99/06507 60 e Ligation activity (in addition to cleavage activity) makes ribozyme amenable to engineering through in vitro selection [3] e Complete kinetic framework established for one 5 ribozyme [6] . * Chemical modification investigation of important residues begun [37 ,38] . Hepatitis Delta Virus (HDV) Ribozyme e Size: -60 nucleotides. 10 - Trans cleavage of target RNAs demonstrated []. 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. Hegg, Lisa A.; Fedor, Martha J.. Kinetics and Thermodynamics of Intermolecular catalysis by Hairpin Ribozymes. Biochemistry (1995), 34(48), 15813-28. 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), 34(12), 4068-76. 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(4), 573-81. 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.

WO 99/50403 PCT/US99/06507 61 Binding sites and structural requirements not fully determined, although no sequences 5' of cleavage site are required. Folded ribozyme contains a pseudoknot structure [40]. 5 - 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. 10 e Circular form of HDV is active and shows increased nuclease stability [41] Lo 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), 434-6. AL Puttaraju, M.; Perrotta, Anne T.; Been, Michael D.. A circular trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res. (1993), 21(18), 4253-8.

WO 99/50403 PCT/US99/06507 62 Table II: 2.5 pmol RNA Synthesis Cycle Reagent Equivalents Amount Time* Phosphoramidites 6.5 163 pL 2.5 S-Ethyl Tetrazole 23.8 238 pL 2.5 5 Acetic Anhydride 100 233 pL 5 sec N-Methyl Imidazole 186 233 pL 5 sec TCA 83.2 1.73 mL 21 sec Iodine 8.0 1.18 mL 45 sec Acetonitrile NA 6.67 mL NA 10 * Wait time does not include contact time during delivery.

WO 99/50403 PCT/US99/06507 63 TABLE III: HAMMERHEAD RIBOZYME AND SITE SEQUENCES FOR ARNT Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 10 AGUGGGAG CUGAUGAG X CGAA 1 UGGCGGCUC 394 AGCCGCCA CUCCCACU 5 13 CCCAGUGG CUGAUGAG X CGAA 2 CGGCUCCUC 395 AGGAGCCG CCACUGGG 49 UGGCCGCA CUGAUGAG X CGAA 3 GGUGGCAUC 396 AUGCCACC UGCGGCCA 69 GUUGGCAG CUGAUGAG X CGAA 4 CGGCGACUA 397 10 AGUCGCCG CUGCCAAC 91 GUACAUCU CUGAUGAG X CGAA 5 AAUGACAUC 398 AUGUCAUU AGAUGUAC 98 AGUGAUGG CUGAUGAG X CGAA 6 UCAGAUGUA 399 ACAUCUGA CCAUCACU 15 103 GACCCAGU CUGAUGAG X CGAA 7 UGUACCAUC 400 AUGGUACA ACUGGGUC 111 AAUGGCUG CUGAUGAG X CGAA 8 CACUGGGUC 401 ACCCAGUG CAGCCAUU 119 CCAGAGGC CUGAUGAG X CGAA 9 CCAGCCAUU 402 20 AUGGCUGG GCCUCUGG 124 AGUUUCCA CUGAUGAG X CGAA 10 CAUUGCCUC 403 AGGCAAUG UGGAAACU 133 CAGGUCCA CUGAUGAG X CGAA 11 UGGAAACUC 404 AGUUUCCA UGGACCUG 25 146 CCACCUUG CUGAUGAG X CGAA 12 CCUGGAAUU 405 AUUCCAGG CAAGGUGG 147 UCCACCUU CUGAUGAG X CGAA 13 CUGGAAUUC 406 AAUUCCAG AAGGUGGA 164 CUCUGGAC CUGAUGAG X CGAA 14 GGAGCCAUU 407 30 AUGGCUCC GUCCAGAG 167 GCCCUCUG CUGAUGAG X CGAA 15 GCCAUUGUC 408 ACAAUGGC

CAGAGGGC

WO 99/50403 PCT/US99/06507 64 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 177 CCGCUUAA CUGAUGAG X CGAA 16 AGAGGGCUA 409 AGCCCUCU UUAAGCGG 5 179 CGCCGCUU CUGAUGAG X CGAA 17 AGGGCUAUU 410 AUAGCCCU AAGCGGCG 180 UCGCCGCU CUGAUGAG X CGAA 18 GGGCUAUUA 411 AAUAGCCC AGCGGCGA 201 AUCAUCAA CUGAUGAG X CGAA 19 GGCUGGAUU 412 10 AUCCAGCC UUGAUGAU 202 CAUCAUCA CUGAUGAG X CGAA 20 GCUGGAUUU 413 AAUCCAGC UGAUGAUG 203 UCAUCAUC CUGAUGAG X CGAA 21 CUGGAUUUU 414 AAAUCCAG GAUGAUGA 15 228 CAAAAAUU CUGAUGAG X CGAA 22 GGAACAGUA 415 ACUGUUCC AAUUUUUG 232 ACCUCAAA CUGAUGAG X CGAA 23 CAGUAAAUU 416 AUUUACUG UUUGAGGU 233 CACCUCAA CUGAUGAG X CGAA 24 AGUAAAUUU 417 20 AAUUUACU UUGAGGUG 234 ACACCUCA CUGAUGAG X CGAA 25 GUAAAUUUU 418 AAAUUUAC UGAGGUGU 235 CACACCUC CUGAUGAG X CGAA 26 UAAAUUUUU 419 AAAAUUUA GAGGUGUG 25 252 AGACAUCU CUGAUGAG X CGAA 27 AUGAUGAUC 420 AUCAUCAU AGAUGUCU 259 UAUCGUUA CUGAUGAG X CGAA 28 UCAGAUGUC 421 ACAUCUGA UAACGAUA 261 CUUAUCGU CUGAUGAG X CGAA 29 AGAUGUCUA 422 30 AGACAUCU ACGAUAAG 267 CCGCUCCU CUGAUGAG X CGAA 30 CUAACGAUA 423 AUCGUUAG AGGAGCGG 277 ACCUGGCA CUGAUGAG X CGAA 31 GGAGCGGUU 424 ACCGCUCC UGCCAGGU WO 99/50403 PCTIUS99/06507 65 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 278 GACCUGGC CUGAUGAG X CGAA 32 GAGCGGUUU 425 AACCGCUC GCCAGGUC 5 286 CAUCAUCC CUGAUGAG X CGAA 33 UGCCAGGUC 426 ACCUGGCA GGAUGAUG 304 UAUCCGCA CUGAUGAG X CGAA 34 GCAGAGCUC 427 AGCUCUGC UGCGGAUA 312 UCUCUCUU CUGAUGAG X CGAA 35 CUGCGGAUA 428 10 AUCCGCAG AAGAGAGA 323 UCCCUGGC CUGAUGAG X CGAA 36 GAGAGACUU 429 AGUCUCUC GCCAGGGA 336 UUCACUGU CUGAUGAG X CGAA 37 GGGAAAAUC 430 AUUUUCCC ACAGUGAA 15 347 CGCCGUUC CUGAUGAG X CGAA 38 AGUGAAAUU 431 AUUUCACU GAACGGCG 379 CUGUGAUG CUGAUGAG X CGAA 39 GACAGCCUA 432 AGGCUGUC CAUCACAG 383 AGUUCUGU CUGAUGAG X CGAA 40 GCCUACAUC 433 20 AUGUAGGC ACAGAACU 394 CCAUAUCU CUGAUGAG X CGAA 41 AGAACUGUC 434 ACAGUUCU AGAUAUGG 399 GGGUACCA CUGAUGAG X CGAA 42 UGUCAGAUA 435 AUCUGACA UGGUACCC 25 404 CAGGUGGG CUGAUGAG X CGAA 43 GAUAUGGUA 436 ACCAUAUC CCCACCUG 414 CAGGGCAC CUGAUGAG X CGAA 44 CCACCUGUA 437 ACAGGUGG GUGCCCUG 426 UGGUUUUC CUGAUGAG X CGAA 45 CCCUGGCUC 438 30 AGCCAGGG GAAAACCA 443 AAGAUGGU CUGAUGAG X CGAA 46 GACAAGCUA 439 AGCUUGUC ACCAUCUU 449 AUGCGUAA CUGAUGAG X CGAA 47 CUAACCAUC 440 AUGGUUAG UUACGCAU WO 99/50403 PCTIUS99/06507 66 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 451 CCAUGCGU CUGAUGAG X CGAA 48 AACCAUCUU 441 AGAUGGUU ACGCAUGG 5 452 GCCAUGCG CUGAUGAG X CGAA 49 ACCAUCUUA 442 AAGAUGGU CGCAUGGC 464 AUGUGAGA CUGAUGAG X CGAA 50 AUGGCAGUU 443 ACUGCCAU UCUCACAU 465 CAUGUGAG CUGAUGAG X CGAA 51 UGGCAGUUU 444 10 AACUGCCA CUCACAUG 466 UCAUGUGA CUGAUGAG X CGAA 52 GGCAGUUUC 445 AAACUGCC UCACAUGA 468 CUUCAUGU CUGAUGAG X CGAA 53 CAGUUUCUC 446 AGAAACUG ACAUGAAG 15 478 CCCGCAAG CUGAUGAG X CGAA 54 CAUGAAGUC 447 ACUUCAUG CUUGCGGG 481 UUCCCCGC CUGAUGAG X CGAA 55 GAAGUCCUU 448 AGGACUUC GCGGGGAA 502 CAUCAGUG CUGAUGAG X CGAA 56 CAACACAUC 449 20 AUGUGUUG CACUGAUG 514 GCUUAUAG CUGAUGAG X CGAA 57 UGAUGGCUC 450 AGCCAUCA CUAUAAGC 517 ACGGCUUA CUGAUGAG X CGAA 58 UGGCUCCUA 451 AGGAGCCA UAAGCCGU 25 519 AGACGGCU CUGAUGAG X CGAA 59 GCUCCUAUA 452 AUAGGAGC AGCCGUCU 526 UGAGGAAA CUGAUGAG X CGAA 60 UAAGCCGUC 453 ACGGCUUA UUUCCUCA 528 AGUGAGGA CUGAUGAG X CGAA 61 AGCCGUCUU 454 30 AGACGGCU UCCUCACU 529 CAGUGAGG CUGAUGAG X CGAA 62 GCCGUCUUU 455 AAGACGGC CCUCACUG 530 UCAGUGAG CUGAUGAG X CGAA 63 CCGUCUUUC 456 AAAGACGG CUCACUGA WO 99/50403 PCTIUS99/06507 67 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 533 UGAUCAGU CUGAUGAG X CGAA 64 UCUUUCCUC 457 AGGAAAGA ACUGAUCA 5 540 CAGUUCCU CUGAUGAG X CGAA 65 UCACUGAUC 458 AUCAGUGA AGGAACUG 555 CAAGAUCA CUGAUGAG X CGAA 66 UGAAACAUU 459 AUGUUUCA UGAUCUUG 556 CCAAGAUC CUGAUGAG X CGAA 67 GAAACAUUU 460 10 AAUGUUUC GAUCUUGG 560 GCCUCCAA CUGAUGAG X CGAA 68 CAUUUGAUC 461 AUCAAAUG UUGGAGGC 562 CUGCCUCC CUGAUGAG X CGAA 69 UUUGAUCUU 462 AGAUCAAA GGAGGCAG 15 580 UAAACAGA CUGAUGAG X CGAA 70 AGAUGGCUU 463 AGCCAUCU UCUGUUUA 581 AUAAACAG CUGAUGAG X CGAA 71 GAUGGCUUU 464 AAGCCAUC CUGUUUAU 582 AAUAAACA CUGAUGAG X CGAA 72 AUGGCUUUC 465 20 AAAGCCAU UGUUUAUU 586 AGACAAUA CUGAUGAG X CGAA 73 CUUUCUGUU 466 ACAGAAAG UAUUGUCU 587 GAGACAAU CUGAUGAG X CGAA 74 UUUCUGUUU 467 AACAGAAA AUUGUCUC 25 588 UGAGACAA CUGAUGAG X CGAA 75 UUCUGUUUA 468 AAACAGAA UUGUCUCA 590 CAUGAGAC CUGAUGAG X CGAA 76 CUGUUUAUU 469 AUAAACAG GUCUCAUG 593 UCACAUGA CUGAUGAG X CGAA 77 UUUAUUGUC 470 30 ACAAUAAA UCAUGUGA 595 UCUCACAU CUGAUGAG X CGAA 78 UAUUGUCUC 471 AGACAAUA AUGUGAGA 619 CAGACACA CUGAUGAG X CGAA 79 GGUGGUGUA 472 ACACCACC UGUGUCUG WO 99/50403 PCTIUS99/06507 68 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 625 CGGAGUCA CUGAUGAG X CGAA 80 GUAUGUGUC 473 ACACAUAC UGACUCCG 5 631 GAGUCACG CUGAUGAG X CGAA 81 GUCUGACUC 474 AGUCAGAC CGUGACUC 639 CAAAACAG CUGAUGAG X CGAA 82 CCGUGACUC 475 AGUCACGG CUGUUUUG 644 UGGUUCAA CUGAUGAG X CGAA 83 ACUCCUGUU 476 10 ACAGGAGU UUGAACCA 645 CUGGUUCA CUGAUGAG X CGAA 84 CUCCUGUUU 477 AACAGGAG UGAACCAG 646 GCUGGUUC CUGAUGAG X CGAA 85 UCCUGUUUU 478 AAACAGGA GAACCAGC 15 661 ACCAUUCA CUGAUGAG X CGAA 86 GCCACAGUC 479 ACUGUGGC UGAAUGGU 670 UGCUGCCA CUGAUGAG X CGAA 87 UGAAUGGUU 480 ACCAUUCA UGGCAGCA 671 GUGCUGCC CUGAUGAG X CGAA 88 GAAUGGUUU 481 20 AACCAUUC GGCAGCAC 683 UGAUCAUA CUGAUGAG X CGAA 89 AGCACACUC 482 AGUGUGCU UAUGAUCA 685 CCUGAUCA CUGAUGAG X CGAA 90 CACACUCUA 483 AGAGUGUG UGAUCAGG 25 690 GUGCACCU CUGAUGAG X CGAA 91 UCUAUGAUC 484 AUCAUAGA AGGUGCAC 714 ACGAAGUU CUGAUGAG X CGAA 92 AUGUGGAUA 485 AUCCACAU AACUUCGU 719 UGCUCACG CUGAUGAG X CGAA 93 GAUAAACUU 486 30 AGUUUAUC CGUGAGCA 720 CUGCUCAC CUGAUGAG X CGAA 94 AUAAACUUC 487 AAGUUUAU GUGAGCAG 731 GAAGUGGA CUGAUGAG X CGAA 95 GAGCAGCUU 488 AGCUGCUC UCCACUUC WO 99/50403 PCTIUS99/06507 69 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 732 UGAAGUGG CUGAUGAG X CGAA 96 AGCAGCUUU 489 AAGCUGCU CCACUUCA 5 733 CUGAAGUG CUGAUGAG X CGAA 97 GCAGCUUUC 490 AAAGCUGC CACUUCAG 738 AUUUUCUG CUGAUGAG X CGAA 98 UUUCCACUU 491 AGUGGAAA CAGAAAAU 739 CAUUUUCU CUGAUGAG X CGAA 99 UUCCACUUC 492 10 AAGUGGAA AGAAAAUG 762 AUCCAGGA CUGAUGAG X CGAA 100 CAGGGCGUA 493 ACGCCCUG UCCUGGAU 764 AGAUCCAG CUGAUGAG X CGAA 101 GGGCGUAUC 494 AUACGCCC CUGGAUCU 15 771 AGUCUUUA CUGAUGAG X CGAA 102 UCCUGGAUC 495 AUCCAGGA UAAAGACU 773 CCAGUCUU CUGAUGAG X CGAA 103 CUGGAUCUA 496 AGAUCCAG AAGACUGG 801 AGACUGCU CUGAUGAG X CGAA 104 AGGAAGGUC 497 20 ACCUUCCU AGCAGUCU 808 UCAUGGAA CUGAUGAG X CGAA 105 UCAGCAGUC 498 ACUGCUGA UUCCAUGA 810 UCUCAUGG CUGAUGAG X CGAA 106 AGCAGUCUU 499 AGACUGCU CCAUGAGA 25 811 UUCUCAUG CUGAUGAG X CGAA 107 GCAGUCUUC 500 AAGACUGC CAUGAGAA 825 UGAGCCCA CUGAUGAG X CGAA 108 GAAUGUGUA 501 ACACAUUC UGGGCUCA 832 AUCUCCUU CUGAUGAG X CGAA 109 UAUGGGCUC 502 30 AGCCCAUA AAGGAGAU 841 AAAUAAAC CUGAUGAG X CGAA 110 AAGGAGAUC 503 AUCUCCUU GUUUAUUU 844 GGCAAAUA CUGAUGAG X CGAA 111 GAGAUCGUU 504 ACGAUCUC UAUUUGCC WO 99/50403 PCTIUS99/06507 70 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 845 CGGCAAAU CUGAUGAG X CGAA 112 AGAUCGUUU 505 AACGAUCU AUUUGCCG 5 846 UCGGCAAA CUGAUGAG X CGAA 113 GAUCGUUUA 506 AAACGAUC UUUGCCGA 848 AUUCGGCA CUGAUGAG X CGAA 114 UCGUUUAUU 507 AUAAACGA UGCCGAAU 849 CAUUCGGC CUGAUGAG X CGAA 115 CGUUUAUUU 508 10 AAUAAACG GCCGAAUG 870 CACAGAGC CUGAUGAG X CGAA 116 GUGGCAGUA 509 ACUGCCAC GCUCUGUG 874 GGUCCACA CUGAUGAG X CGAA 117 CAGUAGCUC 510 AGCUACUG UGUGGACC 15 887 UUCACAGA CUGAUGAG X CGAA 118 GACCCAGUU 511 ACUGGGUC UCUGUGAA 888 AUUCACAG CUGAUGAG X CGAA 119 ACCCAGUUU 512 AACUGGGU CUGUGAAU 889 UAUUCACA CUGAUGAG X CGAA 120 CCCAGUUUC 513 20 AAACUGGG UGUGAAUA 897 GCUCAGCC CUGAUGAG X CGAA 121 CUGUGAAUA 514 AUUCACAG GGCUGAGC 907 UCCUCACA CUGAUGAG X CGAA 122 GCUGAGCUU 515 AGCUCAGC UGUGAGGA 25 908 UUCCUCAC CUGAUGAG X CGAA 123 CUGAGCUUU 516 AAGCUCAG GUGAGGAA 935 ACAGAGCC CUGAUGAG X CGAA 124 AAUGGACUU 517 AGUCCAUU GGCUCUGU 940 CCUUUACA CUGAUGAG X CGAA 125 ACUUGGCUC 518 30 AGCCAAGU UGUAAAGG 944 CCAUCCUU CUGAUGAG X CGAA 126 GGCUCUGUA 519 ACAGAGCC AAGGAUGG 960 CACGAAGU CUGAUGAG X CGAA 127 GGGAACCUC 520 AGGUUCCC ACUUCGUG WO 99/50403 PCT/US99/06507 71 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 964 CCACCACG CUGAUGAG X CGAA 128 ACCUCACUU 521 AGUGAGGU CGUGGUGG 5 965 ACCACCAC CUGAUGAG X CGAA 129 CCUCACUUC 522 AAGUGAGG GUGGUGGU 974 GUGCAGUG CUGAUGAG X CGAA 130 GUGGUGGUC 523 ACCACCAC CACUGCAC 988 CCUUGAUG CUGAUGAG X CGAA 131 CACAGGCUA 524 10 AGCCUGUG CAUCAAGG 992 CAGGCCUU CUGAUGAG X CGAA 132 GGCUACAUC 525 AUGUAGCC AAGGCCUG 1016 GGGAGGGA CUGAUGAG X CGAA 133 GCAGGUGUU 526 ACACCUGC UCCCUCCC 15 1017 UGGGAGGG CUGAUGAG X CGAA 134 CAGGUGUUU 527 AACACCUG CCCUCCCA 1018 CUGGGAGG CUGAUGAG X CGAA 135 AGGUGUUUC 528 AAACACCU CCUCCCAG 1022 UCAUCUGG CUGAUGAG X CGAA 136 GUUUCCCUC 529 20 AGGGAAAC CCAGAUGA 1060 CUAGGCAA CUGAUGAG X CGAA 137 AAGCAAGUU 530 ACUUGCUU UUGCCUAG 1061 ACUAGGCA CUGAUGAG X CGAA 138 AGCAAGUUU 531 AACUUGCU UGCCUAGU 25 1062 CACUAGGC CUGAUGAG X CGAA 139 GCAAGUUUU 532 AAACUUGC GCCUAGUG 1067 AUGGCCAC CUGAUGAG X CGAA 140 UUUUGCCUA 533 AGGCAAAA GUGGCCAU 1076 AAUCUGCC CUGAUGAG X CGAA 141 GUGGCCAUU 534 30 AUGGCCAC GGCAGAUU 1084 UUACCUGC CUGAUGAG X CGAA 142 UGGCAGAUU 535 AUCUGCCA GCAGGUAA 1091 GAACUAGU CUGAUGAG X CGAA 143 UUGCAGGUA 536 ACCUGCAA ACUAGUUC WO 99/50403 PCTIUS99/06507 72 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1095 GGGAGAAC CUGAUGAG X CGAA 144 AGGUAACUA 537 AGUUACCU GUUCUCCC 5 1098 GUUGGGAG CUGAUGAG X CGAA 145 UAACUAGUU 538 ACUAGUUA CUCCCAAC 1099 AGUUGGGA CUGAUGAG X CGAA 146 AACUAGUUC 539 AACUAGUU UCCCAACU 1101 ACAGUUGG CUGAUGAG X CGAA 147 CUAGUUCUC 540 10 AGAACUAG CCAACUGU 1110 CAUGUCUG CUGAUGAG X CGAA 148 CCAACUGUA 541 ACAGUUGG CAGACAUG 1122 ACAAACAU CUGAUGAG X CGAA 149 ACAUGAGUA 542 ACUCAUGU AUGUUUGU 15 1127 GGUUGACA CUGAUGAG X CGAA 150 AGUAAUGUU 543 ACAUUACU UGUCAACC 1128 UGGUUGAC CUGAUGAG X CGAA 151 GUAAUGUUU 544 AACAUUAC GUCAACCA 1131 UGUUGGUU CUGAUGAG X CGAA 152 AUGUUUGUC 545 20 ACAAACAU AACCAACA 1144 GGGAGAUG CUGAUGAG X CGAA 153 AACAGAGUU 546 ACUCUGUU CAUCUCCC 1145 CGGGAGAU CUGAUGAG X CGAA 154 ACAGAGUUC 547 AACUCUGU AUCUCCCG 25 1148 UGUCGGGA CUGAUGAG X CGAA 155 GAGUUCAUC 548 AUGAACUC UCCCGACA 1150 UGUGUCGG CUGAUGAG X CGAA 156 GUUCAUCUC 549 AGAUGAAC CCGACACA 1163 AUACCCUC CUGAUGAG X CGAA 157 CACAACAUU 550 30 AUGUUGUG GAGGGUAU 1170 AGUGAAGA CUGAUGAG X CGAA 158 UUGAGGGUA 551 ACCCUCAA UCUUCACU 1172 AAAGUGAA CUGAUGAG X CGAA 159 GAGGGUAUC 552 AUACCCUC

UUCACUUU

WO 99/50403 PCT/US99/06507 73 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1174 CAAAAGUG CUGAUGAG X CGAA 160 GGGUAUCUU 553 AGAUACCC CACUUUUG 5 1175 ACAAAAGU CUGAUGAG X CGAA 161 GGUAUCUUC 554 AAGAUACC ACUUUUGU 1179 AUCCACAA CUGAUGAG X CGAA 162 UCUUCACUU 555 AGUGAAGA UUGUGGAU 1180 GAUCCACA CUGAUGAG X CGAA 163 CUUCACUUU 556 10 AAGUGAAG UGUGGAUC 1181 UGAUCCAC CUGAUGAG X CGAA 164 UUCACUUUU 557 AAAGUGAA GUGGAUCA 1188 ACAGCGGU CUGAUGAG X CGAA 165 UUGUGGAUC 558 AUCCACAA ACCGCUGU 15 1203 GCCAACAG CUGAUGAG X CGAA 166 GUGUGGCUA 559 AGCCACAC CUGUUGGC 1208 UGGUAGCC CUGAUGAG X CGAA 167 GCUACUGUU 560 ACAGUAGC GGCUACCA 1213 GUGGCUGG CUGAUGAG X CGAA 168 UGUUGGCUA 561 20 AGCCAACA CCAGCCAC 1229 UUUCCUAA CUGAUGAG X CGAA 169 CAGGAACUC 562 AGUUCCUG UUAGGAAA 1231 UCUUUCCU CUGAUGAG X CGAA 170 GGAACUCUU 563 AGAGUUCC AGGAAAGA 25 1232 UUCUUUCC CUGAUGAG X CGAA 171 GAACUCUUA 564 AAGAGUUC GGAAAGAA 1242 UUCUACAA CUGAUGAG X CGAA 172 GAAAGAAUA 565 AUUCUUUC UUGUAGAA 1244 AAUUCUAC CUGAUGAG X CGAA 173 AAGAAUAUU 566 30 AUAUUCUU GUAGAAUU 1247 CAGAAUUC CUGAUGAG X CGAA 174 AAUAUUGUA 567 ACAAUAUU GAAUUCUG 1252 GAUGACAG CUGAUGAG X CGAA 175 UGUAGAAUU 568 AUUCUACA CUGUCAUC WO 99/50403 PCT/US99/06507 74 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1253 GGAUGACA CUGAUGAG X CGAA 176 GUAGAAUUC 569 AAUUCUAC UGUCAUCC 5 1257 UUCAGGAU CUGAUGAG X CGAA 177 AAUUCUGUC 570 ACAGAAUU AUCCUGAA 1260 GUCUUCAG CUGAUGAG X CGAA 178 UCUGUCAUC 571 AUGACAGA CUGAAGAC 1277 UCUCUUAG CUGAUGAG X CGAA 179 CAGCAGCUU 572 10 AGCUGCUG CUAAGAGA 1278 GUCUCUUA CUGAUGAG X CGAA 180 AGCAGCUUC 573 AAGCUGCU UAAGAGAC 1280 CUGUCUCU CUGAUGAG X CGAA 181 CAGCUUCUA 574 AGAAGCUG AGAGACAG 15 1291 CCUGUUGG CUGAUGAG X CGAA 182 AGACAGCUU 575 AGCUGUCU CCAACAGG 1292 ACCUGUUG CUGAUGAG X CGAA 183 GACAGCUUC 576 AAGCUGUC CAACAGGU 1301 AAUUUCAC CUGAUGAG X CGAA 184 CAACAGGUA 577 20 ACCUGUUG GUGAAAUU 1309 GGCCUUUU CUGAUGAG X CGAA 185 AGUGAAAUU 578 AUUUCACU AAAAGGCC 1310 UGGCCUUU CUGAUGAG X CGAA 186 GUGAAAUUA 579 AAUUUCAC AAAGGCCA 25 1327 ACAUGACA CUGAUGAG X CGAA 187 AGUGCUGUC 580 ACAGCACU UGUCAUGU 1331 CGGAACAU CUGAUGAG X CGAA 188 CUGUCUGUC 581 ACAGACAG AUGUUCCG 1336 GGAACCGG CUGAUGAG X CGAA 189 UGUCAUGUU 582 30 ACAUGACA CCGGUUCC 1337 CGGAACCG CUGAUGAG X CGAA 190 GUCAUGUUC 583 AACAUGAC CGGUUCCG 1342 UAGACCGG CUGAUGAG X CGAA 191 GUUCCGGUU 584 ACCGGAAC CCGGUCUA WO 99/50403 PCT/US99/06507 75 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1343 UUAGACCG CUGAUGAG X CGAA 192 UUCCGGUUC 585 AACCGGAA CGGUCUAA 5 1348 GGUUCUUA CUGAUGAG X CGAA 193 GUUCCGGUC 586 ACCGGAAC UAAGAACC 1350 UUGGUUCU CUGAUGAG X CGAA 194 UCCGGUCUA 587 AGACCGGA AGAACCAA 1367 CUCAUCCA CUGAUGAG X CGAA 195 GAAUGGCUC 588 10 AGCCAUUC UGGAUGAG 1384 AAGUAAAG CUGAUGAG X CGAA 196 AACCAGCUC 589 AGCUGGUU CUUUACUU 1387 GGAAAGUA CUGAUGAG X CGAA 197 CAGCUCCUU 590 AGGAGCUG UACUUUCC 15 1388 UGGAAAGU CUGAUGAG X CGAA 198 AGCUCCUUU 591 AAGGAGCU ACUUUCCA 1389 CUGGAAAG CUGAUGAG X CGAA 199 GCUCCUUUA 592 AAAGGAGC CUUUCCAG 1392 GUUCUGGA CUGAUGAG X CGAA 200 CCUUUACUU 593 20 AGUAAAGG UCCAGAAC 1393 GGUUCUGG CUGAUGAG X CGAA 201 CUUUACUUU 594 AAGUAAAG CCAGAACC 1394 GGGUUCUG CUGAUGAG X CGAA 202 UUUACUUUC 595 AAAGUAAA CAGAACCC 25 1404 AUCUGAGU CUGAUGAG X CGAA 203 AGAACCCUU 596 AGGGUUCU ACUCAGAU 1405 CAUCUGAG CUGAUGAG X CGAA 204 GAACCCUUA 597 AAGGGUUC CUCAGAUG 1408 UUUCAUCU CUGAUGAG X CGAA 205 CCCUUACUC 598 30 AGUAAGGG AGAUGAAA 1418 AUGUACUC CUGAUGAG X CGAA 206 GAUGAAAUU 599 AUUUCAUC GAGUACAU 1423 AGAUGAUG CUGAUGAG X CGAA 207 AAUUGAGUA 600 ACUCAAUU CAUCAUCU WO 99/50403 PCTIUS99/06507 76 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1427 GUACAGAU CUGAUGAG X CGAA 208 GAGUACAUC 601 AUGUACUC AUCUGUAC 5 1430 UUGGUACA CUGAUGAG X CGAA 209 UACAUCAUC 602 AUGAUGUA UGUACCAA 1434 GGUGUUGG CUGAUGAG X CGAA 210 UCAUCUGUA 603 ACAGAUGA CCAACACC 1456 CUUGGCUA CUGAUGAG X CGAA 211 GAAGAACUC 604 10 AGUUCUUC UAGCCAAG 1458 UUCUUGGC CUGAUGAG X CGAA 212 AGAACUCUA 605 AGAGUUCU GCCAAGAA 1476 GGAGAGUG CUGAUGAG X CGAA 213 CACGGCCUA 606 AGGCCGUG CACUCUCC 15 1481 GUGUUGGA CUGAUGAG X CGAA 214 CCUACACUC 607 AGUGUAGG UCCAACAC 1483 UUGUGUUG CUGAUGAG X CGAA 215 UACACUCUC 608 AGAGUGUA CAACACAA 1493 GGCCUCUG CUGAUGAG X CGAA 216 AACACAAUC 609 20 AUUGUGUU CAGAGGCC 1508 GUGGGACC CUGAUGAG X CGAA 217 CCACAACUA 610 AGUUGUGG GGUCCCAC 1512 AGCUGUGG CUGAUGAG X CGAA 218 AACUAGGUC 611 ACCUAGUU CCACAGCU 25 1521 GGGUAAAU CUGAUGAG X CGAA 219 CCACAGCUA 612 AGCUGUGG AUUUACCC 1524 CAGGGGUA CUGAUGAG X CGAA 220 CAGCUAAUU 613 AUUAGCUG UACCCCUG 1525 CCAGGGGU CUGAUGAG X CGAA 221 AGCUAAUUU 614 30 AAUUAGCU ACCCCUGG 1526 UCCAGGGG CUGAUGAG X CGAA 222 GCUAAUUUA 615 AAAUUAGC CCCCUGGA 1543 GCUGUCCU CUGAUGAG X CGAA 223 GAUGGGCUC 616 AGCCCAUC AGGACAGC WO 99/50403 PCTIUS99/06507 77 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1585 CCAUGUCC CUGAUGAG X CGAA 224 AACAGAAUU 617 AUUCUGUU GGACAUGG 5 1595 CUUCCUGG CUGAUGAG X CGAA 225 GACAUGGUA 618 ACCAUGUC CCAGGAAG 1621 AAUGAUUG CUGAUGAG X CGAA 226 GGCCAGCUA 619 AGCUGGCC CAAUCAUU 1626 CUGGGAAU CUGAUGAG X CGAA 227 GCUACAAUC 620 10 AUUGUAGC AUUCCCAG 1629 CACCUGGG CUGAUGAG X CGAA 228 ACAAUCAUU 621 AUGAUUGU CCCAGGUG 1630 CCACCUGG CUGAUGAG X CGAA 229 CAAUCAUUC 622 AAUGAUUG CCAGGUGG 15 1640 ACAGGCUG CUGAUGAG X CGAA 230 CAGGUGGUU 623 ACCACCUG CAGCCUGU 1641 CACAGGCU CUGAUGAG X CGAA 231 AGGUGGUUC 624 AACCACCU AGCCUGUG 1682 GACUUCUC CUGAUGAG X CGAA 232 AAGCCCCUU 625 20 AGGGGCUU GAGAAGUC 1690 AACCAUCU CUGAUGAG X CGAA 233 UGAGAAGUC 626 ACUUCUCA AGAUGGUU 1698 GGCAAAUA CUGAUGAG X CGAA 234 CAGAUGGUU 627 ACCAUCUG UAUUUGCC 25 1699 GGGCAAAU CUGAUGAG X CGAA 235 AGAUGGUUU 628 AACCAUCU AUUUGCCC 1700 UGGGCAAA CUGAUGAG X CGAA 236 GAUGGUUUA 629 AAACCAUC UUUGCCCA 1702 CCUGGGCA CUGAUGAG X CGAA 237 UGGUUUAUU 630 30 AUAAACCA UGCCCAGG 1703 UCCUGGGC CUGAUGAG X CGAA 238 GGUUUAUUU 631 AAUAAACC GCCCAGGA 1713 UGGAUCUC CUGAUGAG X CGAA 239 CCCAGGAUA 632 AUCCUGGG GAGAUCCA WO 99/50403 PCT/US99/06507 78 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1719 AAAUCUUG CUGAUGAG X CGAA 240 AUAGAGAUC 633 AUCUCUAU CAAGAUUU 5 1726 UUUCUGAA CUGAUGAG X CGAA 241 UCCAAGAUU 634 AUCUUGGA UUCAGAAA 1727 AUUUCUGA CUGAUGAG X CGAA 242 CCAAGAUUU 635 AAUCUUGG UCAGAAAU 1728 GAUUUCUG CUGAUGAG X CGAA 243 CAAGAUUUU 636 10 AAAUCUUG CAGAAAUC 1729 AGAUUUCU CUGAUGAG X CGAA 244 AAGAUUUUC 637 AAAAUCUU AGAAAUCU 1736 UUGUGAUA CUGAUGAG X CGAA 245 UCAGAAAUC 638 AUUUCUGA UAUCACAA 15 1738 UGUUGUGA CUGAUGAG X CGAA 246 AGAAAUCUA 639 AGAUUUCU UCACAACA 1740 GAUGUUGU CUGAUGAG X CGAA 247 AAAUCUAUC 640 AUAGAUUU ACAACAUC 1748 UCCGCAUU CUGAUGAG X CGAA 248 CACAACAUC 641 20 AUGUUGUG AAUGCGGA 1758 UUUACUCU CUGAUGAG X CGAA 249 AUGCGGAUC 642 AUCCGCAU AGAGUAAA 1764 GAUGCCUU CUGAUGAG X CGAA 250 AUCAGAGUA 643 ACUCUGAU AAGGCAUC 25 1772 CUGGAGGA CUGAUGAG X CGAA 251 AAAGGCAUC 644 AUGCCUUU UCCUCCAG 1774 UGCUGGAG CUGAUGAG X CGAA 252 AGGCAUCUC 645 AGAUGCCU CUCCAGCA 1777 CAGUGCUG CUGAUGAG X CGAA 253 CAUCUCCUC 646 30 AGGAGAUG CAGCACUG 1787 GUGGCAGG CUGAUGAG X CGAA 254 AGCACUGUC 647 ACAGUGCU CCUGCCAC 1805 UGGGAGAA CUGAUGAG X CGAA 255 CAACAGCUA 648 AGCUGUUG UUCUCCCA WO 99/50403 PCT/US99/06507 79 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1807 CCUGGGAG CUGAUGAG X CGAA 256 ACAGCUAUU 649 AUAGCUGU CUCCCAGG 5 1808 CCCUGGGA CUGAUGAG X CGAA 257 CAGCUAUUC 650 AAUAGCUG UCCCAGGG 1810 UGCCCUGG CUGAUGAG X CGAA 258 GCUAUUCUC 651 AGAAUAGC CCAGGGCA 1825 UAGGAGGG CUGAUGAG X CGAA 259 CAACACAUU 652 10 AUGUGUUG CCCUCCUA 1826 GUAGGAGG CUGAUGAG X CGAA 260 AACACAUUC 653 AAUGUGUU CCUCCUAC 1830 GGGGGUAG CUGAUGAG X CGAA 261 CAUUCCCUC 654 AGGGAAUG CUACCCCC 15 1833 CCGGGGGG CUGAUGAG X CGAA 262 UCCCUCCUA 655 AGGAGGGA CCCCCCGG 1854 AUUCCUGA CUGAUGAG X CGAA 263 CAGAGAAUU 656 AUUCUCUG UCAGGAAU 1855 UAUUCCUG CUGAUGAG X CGAA 264 AGAGAAUUU 657 20 AAUUCUCU CAGGAAUA 1856 CUAUUCCU CUGAUGAG X CGAA 265 GAGAAUUUC 658 AAAUUCUC AGGAAUAG 1863 UAGGCCAC CUGAUGAG X CGAA 266 UCAGGAAUA 659 AUUCCUGA GUGGCCUA 25 1871 GGAGGGGC CUGAUGAG X CGAA 267 AGUGGCCUA 660 AGGCCACU GCCCCUCC 1878 GGUUACAG CUGAUGAG X CGAA 268 UAGCCCCUC 661 AGGGGCUA CUGUAACC 1883 ACAAUGGU CUGAUGAG X CGAA 269 CCUCCUGUA 662 30 ACAGGAGG ACCAUUGU 1889 GGCUGGAC CUGAUGAG X CGAA 270 GUAACCAUU 663 AUGGUUAC GUCCAGCC 1892 GAUGGCUG CUGAUGAG X CGAA 271 ACCAUUGUC 664 ACAAUGGU CAGCCAUC WO 99/50403 PCT/US99/06507 80 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 1900 CAGAAGCU CUGAUGAG X CGAA 272 CCAGCCAUC 665 AUGGCUGG AGCUUCUG 5 1905 UCCUGCAG CUGAUGAG X CGAA 273 CAUCAGCUU 666 AGCUGAUG CUGCAGGA 1906 GUCCUGCA CUGAUGAG X CGAA 274 AUCAGCUUC 667 AAGCUGAU UGCAGGAC 1921 UCUGGGCC CUGAUGAG X CGAA 275 ACAGAUGUU 668 10 ACAUCUGU GGCCCAGA 1931 UGGCGGGA CUGAUGAG X CGAA 276 GCCCAGAUU 669 AUCUGGGC UCCCGCCA 1932 GUGGCGGG CUGAUGAG X CGAA 277 CCCAGAUUU 670 AAUCUGGG CCCGCCAC 15 1933 AGUGGCGG CUGAUGAG X CGAA 278 CCAGAUUUC 671 AAAUCUGG CCGCCACU 1942 UGGGGUUG CUGAUGAG X CGAA 279 CCGCCACUC 672 AGUGGCGG CAACCCCA 1971 AGGGGUCC CUGAUGAG X CGAA 280 CCCCAACUU 673 20 AGUUGGGG GGACCCCU 1980 GCGGGUAG CUGAUGAG X CGAA 281 GGACCCCUA 674 AGGGGUCC CUACCCGC 1983 UGAGCGGG CUGAUGAG X CGAA 282 CCCCUACUA 675 AGUAGGGG CCCGCUCA 25 1990 AAAAGCCU CUGAUGAG X CGAA 283 UACCCGCUC 676 AGCGGGUA AGGCUUUU 1996 GGGCAGAA CUGAUGAG X CGAA 284 CUCAGGCUU 677 AGCCUGAG UUCUGCCC 1997 UGGGCAGA CUGAUGAG X CGAA 285 UCAGGCUUU 678 30 AAGCCUGA UCUGCCCA 1998 CUGGGCAG CUGAUGAG X CGAA 286 CAGGCUUUU 679 AAAGCCUG CUGCCCAG 1999 GCUGGGCA CUGAUGAG X CGAA 287 AGGCUUUUC 680 AAAAGCCU UGCCCAGC WO 99/50403 PCTIUS99/06507 81 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 2016 AGCCUGGG CUGAUGAG X CGAA 288 AGGUGGCUA 681 AGCCACCU CCCAGGCU 5 2025 CUUAGCAG CUGAUGAG X CGAA 289 CCCAGGCUA 682 AGCCUGGG CUGCUAAG 2031 ACGAGUCU CUGAUGAG X CGAA 290 CUACUGCUA 683 AGCAGUAG AGACUCGU 2037 GGAAGUAC CUGAUGAG X CGAA 291 CUAAGACUC 684 10 AGUCUUAG GUACUUCC 2040 CUGGGAAG CUGAUGAG X CGAA 292 AGACUCGUA 685 ACGAGUCU CUUCCCAG 2043 AAACUGGG CUGAUGAG X CGAA 293 CUCGUACUU 686 AGUACGAG CCCAGUUU 15 2044 CAAACUGG CUGAUGAG X CGAA 294 UCGUACUUC 687 AAGUACGA CCAGUUUG 2050 CCACACCA CUGAUGAG X CGAA 295 UUCCCAGUU 688 ACUGGGAA UGGUGUGG 2051 CCCACACC CUGAUGAG X CGAA 296 UCCCAGUUU 689 20 AACUGGGA GGUGUGGG 2065 GAGUCUGA CUGAUGAG X CGAA 297 GGGCAGCUU 690 AGCUGCCC UCAGACUC 2066 GGAGUCUG CUGAUGAG X CGAA 298 GGCAGCUUU 691 AAGCUGCC CAGACUCC 25 2067 UGGAGUCU CUGAUGAG X CGAA 299 GCAGCUUUC 692 AAAGCUGC AGACUCCA 2073 GGAGGAUG CUGAUGAG X CGAA 300 UUCAGACUC 693 AGUCUGAA CAUCCUCC 2077 UGAAGGAG CUGAUGAG X CGAA 301 GACUCCAUC 694 30 AUGGAGUC CUCCUUCA 2080 AGCUGAAG CUGAUGAG X CGAA 302 UCCAUCCUC 695 AGGAUGGA CUUCAGCU 2083 UGGAGCUG CUGAUGAG X CGAA 303 AUCCUCCUU 696 AGGAGGAU CAGCUCCA WO 99/50403 PCT/US99/06507 82 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 2084 AUGGAGCU CUGAUGAG X CGAA 304 UCCUCCUUC 697 AAGGAGGA AGCUCCAU 5 2089 GGGACAUG CUGAUGAG X CGAA 305 CUUCAGCUC 698 AGCUGAAG CAUGUCCC 2095 CAGGGAGG CUGAUGAG X CGAA 306 CUCCAUGUC 699 ACAUGGAG CCUCCCUG 2099 GCACCAGG CUGAUGAG X CGAA 307 AUGUCCCUC 700 10 AGGGACAU CCUGGUGC 2119 CACCAGGC CUGAUGAG X CGAA 308 AACUGCAUC 701 AUGCAGUU GCCUGGUG 2137 GACUAGGG CUGAUGAG X CGAA 309 UGCUGCCUA 702 AGGCAGCA CCCUAGUC 15 2142 GGUGAGAC CUGAUGAG X CGAA 310 CCUACCCUA 703 AGGGUAGG GUCUCACC 2145 AUUGGUGA CUGAUGAG X CGAA 311 ACCCUAGUC 704 ACUAGGGU UCACCAAU 2147 CGAUUGGU CUGAUGAG X CGAA 312 CCUAGUCUC 705 20 AGACUAGG ACCAAUCG 2154 AGAUCCAC CUGAUGAG X CGAA 313 UCACCAAUC 706 AUUGGUGA GUGGAUCU 2161 CAAAGUUA CUGAUGAG X CGAA 314 UCGUGGAUC 707 AUCCACGA UAACUUUG 25 2163 AGCAAAGU CUGAUGAG X CGAA 315 GUGGAUCUA 708 AGAUCCAC ACUUUGCU 2167 CAGGAGCA CUGAUGAG X CGAA 316 AUCUAACUU 709 AGUUAGAU UGCUCCUG 2168 UCAGGAGC CUGAUGAG X CGAA 317 UCUAACUUU 710 30 AAGUUAGA GCUCCUGA 2172 AGUCUCAG CUGAUGAG X CGAA 318 ACUUUGCUC 711 AGCAAAGU CUGAGACU 2200 GUGUCUGG CUGAUGAG X CGAA 319 AGGACAAUU 712 AUUGUCCU CCAGACAC WO 99/50403 PCT/US99/06507 83 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 2201 CGUGUCUG CUGAUGAG X CGAA 320 GGACAAUUC 713 AAUUGUCC CAGACACG 5 2231 UGUGGCCA CUGAUGAG X CGAA 321 GUGGGUGUC 714 ACACCCAC UGGCCACA 2259 ACGAUGAU CUGAUGAG X CGAA 322 AGCAGCCUC 715 AGGCUGCU AUCAUCGU 2262 UGAACGAU CUGAUGAG X CGAA 323 AGCCUCAUC 716 10 AUGAGGCU AUCGUUCA 2265 ACUUGAAC CUGAUGAG X CGAA 324 CUCAUCAUC 717 AUGAUGAG GUUCAAGU 2268 AGAACUUG CUGAUGAG X CGAA 325 AUCAUCGUU 718 ACGAUGAU CAAGUUCU 15 2269 UAGAACUU CUGAUGAG X CGAA 326 UCAUCGUUC 719 AACGAUGA AAGUUCUA 2274 CUCACUAG CUGAUGAG X CGAA 327 GUUCAAGUU 720 ACUUGAAC CUAGUGAG 2275 GCUCACUA CUGAUGAG X CGAA 328 UUCAAGUUC 721 20 AACUUGAA UAGUGAGC 2277 UUGCUCAC CUGAUGAG X CGAA 329 CAAGUUCUA 722 AGAACUUG GUGAGCAA 2291 GGUUGUUG CUGAUGAG X CGAA 330 CAACAUGUU 723 ACAUGUUG CAACAACC 25 2292 CGGUUGUU CUGAUGAG X CGAA 331 AACAUGUUC 724 AACAUGUU AACAACCG 2330 UCCUGGAA CUGAUGAG X CGAA 332 CCUGAGGUC 725 ACCUCAGG UUCCAGGA 2332 UCUCCUGG CUGAUGAG X CGAA 333 UGAGGUCUU 726 30 AGACCUCA CCAGGAGA 2333 AUCUCCUG CUGAUGAG X CGAA 334 GAGGUCUUC 727 AAGACCUC CAGGAGAU 2347 CCAGCAUG CUGAUGAG X CGAA 335 GAUGCUGUC 728 ACAGCAUC CAUGCUGG WO 99/50403 PCTIUS99/06507 84 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 2361 GUUGCUCU CUGAUGAG X CGAA 336 UGGGAGAUC 729 AUCUCCCA AGAGCAAC 5 2374 CAUUGUUG CUGAUGAG X CGAA 337 CAACAGCUA 730 AGCUGUUG CAACAAUG 2389 GAUCAGGG CUGAUGAG X CGAA 338 UGAAGAAUU 731 AUUCUUCA CCCUGAUC 2390 AGAUCAGG CUGAUGAG X CGAA 339 GAAGAAUUC 732 10 AAUUCUUC CCUGAUCU 2397 CAUAGUUA CUGAUGAG X CGAA 340 UCCCUGAUC 733 AUCAGGGA UAACUAUG 2399 AACAUAGU CUGAUGAG X CGAA 341 CCUGAUCUA 734 AGAUCAGG ACUAUGUU 15 2403 GGGAAACA CUGAUGAG X CGAA 342 AUCUAACUA 735 AGUUAGAU UGUUUCCC 2407 AGGGGGGA CUGAUGAG X CGAA 343 AACUAUGUU 736 ACAUAGUU UCCCCCCU 2408 AAGGGGGG CUGAUGAG X CGAA 344 ACUAUGUUU 737 20 AACAUAGU CCCCCCUU 2409 AAAGGGGG CUGAUGAG X CGAA 345 CUAUGUUUC 738 AAACAUAG CCCCCUUU 2416 AUUCUGAA CUGAUGAG X CGAA 346 UCCCCCCUU 739 AGGGGGGA UUCAGAAU 25 2417 UAUUCUGA CUGAUGAG X CGAA 347 CCCCCCUUU 740 AAGGGGGG UCAGAAUA 2418 CUAUUCUG CUGAUGAG X CGAA 348 CCCCCUUUU 741 AAAGGGGG CAGAAUAG 2419 UCUAUUCU CUGAUGAG X CGAA 349 CCCCUUUUC 742 30 AAAAGGGG AGAAUAGA 2425 AAUAGUUC CUGAUGAG X CGAA 350 UUCAGAAUA 743 AUUCUGAA GAACUAUU 2431 CACCCCAA CUGAUGAG X CGAA 351 AUAGAACUA 744 AGUUCUAU UUGGGGUG WO 99/50403 PCTIUS99/06507 85 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 2433 CUCACCCC CUGAUGAG X CGAA 352 AGAACUAUU 745 AUAGUUCU GGGGUGAG 5 2445 CCACCCCU CUGAUGAG X CGAA 353 GUGAGGAUA 746 AUCCUCAC AGGGGUGG 2466 CAAACAGU CUGAUGAG X CGAA 354 GAAAAAAUC 747 AUUUUUUC ACUGUUUG 2472 UAAAAACA CUGAUGAG X CGAA 355 AUCACUGUU 748 10 ACAGUGAU UGUUUUUA 2473 UUAAAAAC CUGAUGAG X CGAA 356 UCACUGUUU 749 AACAGUGA GUUUUUAA 2476 UUUUUAAA CUGAUGAG X CGAA 357 CUGUUUGUU 750 ACAAACAG UUUAAAAA 15 2477 CUUUUUAA CUGAUGAG X CGAA 358 UGUUUGUUU 751 AACAAACA UUAAAAAG 2478 GCUUUUUA CUGAUGAG X CGAA 359 GUUUGUUUU 752 AAACAAAC UAAAAAGC 2479 UGCUUUUU CUGAUGAG X CGAA 360 UUUGUUUUU 753 20 AAAACAAA AAAAAGCA 2480 UUGCUUUU CUGAUGAG X CGAA 361 UUGUUUUUA 754 AAAAACAA AAAAGCAA 2491 UACAGAAA CUGAUGAG X CGAA 362 AAGCAAAUC 755 AUUUGCUU UUUCUGUA 25 2493 UUUACAGA CUGAUGAG X CGAA 363 GCAAAUCUU 756 AGAUUUGC UCUGUAAA 2494 GUUUACAG CUGAUGAG X CGAA 364 CAAAUCUUU 757 AAGAUUUG CUGUAAAC 2495 UGUUUACA CUGAUGAG X CGAA 365 AAAUCUUUC 758 30 AAAGAUUU UGUAAACA 2499 AUUCUGUU CUGAUGAG X CGAA 366 CUUUCUGUA 759 ACAGAAAG AACAGAAU 2508 GGAACUUU CUGAUGAG X CGAA 367 AACAGAAUA 760 AUUCUGUU AAAGUUCC WO 99/50403 PCT/US99/06507 86 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 2514 GGGAGAGG CUGAUGAG X CGAA 368 AUAAAAGUU 761 ACUUUUAU CCUCUCCC 5 2515 AGGGAGAG CUGAUGAG X CGAA 369 UAAAAGUUC 762 AACUUUUA CUCUCCCU 2518 GGAAGGGA CUGAUGAG X CGAA 370 AAGUUCCUC 763 AGGAACUU UCCCUUCC 2520 AGGGAAGG CUGAUGAG X CGAA 371 GUUCCUCUC 764 10 AGAGGAAC CCUUCCCU 2524 GGGAAGGG CUGAUGAG X CGAA 372 CUCUCCCUU 765 AGGGAGAG CCCUUCCC 2525 AGGGAAGG CUGAUGAG X CGAA 373 UCUCCCUUC 766 AAGGGAGA CCUUCCCU 15 2529 GGUGAGGG CUGAUGAG X CGAA 374 CCUUCCCUU 767 AGGGAAGG CCCUCACC 2530 GGGUGAGG CUGAUGAG X CGAA 375 CUUCCCUUC 768 AAGGGAAG CCUCACCC 2534 UCAGGGGU CUGAUGAG X CGAA 376 CCUUCCCUC 769 20 AGGGAAGG ACCCCUGA 2548 AAAGGGGG CUGAUGAG X CGAA 377 UGACAUGUA 770 ACAUGUCA CCCCCUUU 2555 AGAAGGGA CUGAUGAG X CGAA 378 UACCCCCUU 771 AGGGGGUA UCCCUUCU 25 2556 CAGAAGGG CUGAUGAG X CGAA 379 ACCCCCUUU 772 AAGGGGGU CCCUUCUG 2557 CCAGAAGG CUGAUGAG X CGAA 380 CCCCCUUUC 773 AAAGGGGG CCUUCUGG 2561 ACAGCCAG CUGAUGAG X CGAA 381 CUUUCCCUU 774 30 AGGGAAAG CUGGCUGU 2562 AACAGCCA CUGAUGAG X CGAA 382 UUUCCCUUC 775 AAGGGAAA UGGCUGUU 2570 AGCAGGGG CUGAUGAG X CGAA 383 CUGGCUGUU 776 ACAGCCAG CCCCUGCU WO 99/50403 PCT/US99/06507 87 Posi- Seq. Seq. I.D. tion RZ I.D. No. Substrate No. 2571 GAGCAGGG CUGAUGAG X CGAA 384 UGGCUGUUC 777 AACAGCCA CCCUGCUC 5 2579 AGGCAACA CUGAUGAG X CGAA 385 CCCCUGCUC 778 AGCAGGGG UGUUGCCU 2583 UAGGAGGC CUGAUGAG X CGAA 386 UGCUCUGUU 779 ACAGAGCA GCCUCCUA 2588 UACCUUAG CUGAUGAG X CGAA 387 UGUUGCCUC 780 10 AGGCAACA CUAAGGUA 2591 UGUUACCU CUGAUGAG X CGAA 388 UGCCUCCUA 781 AGGAGGCA AGGUAACA 2596 AUAAAUGU CUGAUGAG X CGAA 389 CCUAAGGUA 782 ACCUUAGG ACAUUUAU 15 2601 UUUUUAUA CUGAUGAG X CGAA 390 GGUAACAUU 783 AUGUUACC UAUAAAAA 2602 UUUUUUAU CUGAUGAG X CGAA 391 GUAACAUUU 784 AAUGUUAC AUAAAAAA 2603 UUUUUUUA CUGAUGAG X CGAA 392 UAACAUUUA 785 20 AAAUGUUA UAAAAAAA 2605 UUUUUUUU CUGAUGAG X CGAA 393 ACAUUUAUA 786 AUAAAUGU AAAAAAAA 25 30 WO 99/50403 PCT/US99/06507 88 TABLE IV: HAIRPIN RIBOZYME SEQUENCES AND TARGET SITES FOR ARNT Posi- Seq. I.D. Seq. tion RZ No. Substrate I.D. No. 6 GGGAGG AGAA GCCA ACCAGAGAAACA 787 UGGCG GCU CCUCCC 849 X GUACAUUACCUGGUA 92 UGGUAC AGAA GAUG ACCAGAGAAACA 788 CAUCA GAU GUACCA 850 X GUACAUUACCUGGUA 253 UUAGAC AGAA GAUC ACCAGAGAAACA 789 GAUCA GAU GUCUAA 851 X GUACAUUACCUGGUA 274 CUGGCA AGAA GCUC ACCAGAGAAACA 790 GAGCG GUU UGCCAG 852 .0 X GUACAUUACCUGGUA 287 CUCAUC AGAA GACC ACCAGAGAAACA 791 GGUCG GAU GAUGAG 853 X GUACAUUACCUGGUA 374 GAUGUA AGAA GUCA ACCAGAGAAACA 792 UGACA GCC UACAUC 854 X GUACAUUACCUGGUA 411 GGGCAC AGAA GGUG ACCAGAGAAACA 793 CACCU GUA GUGCCC 855 X GUACAUUACCUGGUA 461 GUGAGA AGAA GCCA ACCAGAGAAACA 794 UGGCA GUU UCUCAC 856 X GUACAUUACCUGGUA 506 GGAGCC AGAA GUGG ACCAGAGAAACA 795 CCACU GAU GGCUCC 857 0 X GUACAUUACCUGGUA 523 AGGAAA AGAA GCUU ACCAGAGAAACA 796 AAGCC GUC UUUCCU 858 X GUACAUUACCUGGUA 536 UUCCUG AGAA GUGA ACCAGAGAAACA 797 UCACU GAU CAGGAA 859 X GUACAUUACCUGGUA 5 572 AAAGCC AGAA GCUG ACCAGAGAAACA 798 CAGCA GAU GGCUUU 860 X GUACAUUACCUGGUA 583 ACAAUA AGAA GAAA ACCAGAGAAACA 799 UUUCU GUU UAUUGU 861 X GUACAUUACCUGGUA 626 CACGGA AGAA GACA ACCAGAGAAACA 800 UGUCU GAC UCCGUG 862 X GUACAUUACCUGGUA 641 GUUCAA AGAA GGAG ACCAGAGAAACA 801 CUCCU GUU UUGAAC 863 X GUACAUUACCUGGUA WO 99/50403 PCT/US99/06507 89 Posi- Seq. I.D. Seq. tion RZ No. Substrate I.D. No. 658 CAUUCA AGAA GUGG ACCAGAGAAACA 802 CCACA GUC UGAAUG 864 X GUACAUUACCUGGUA 5 701 CACAUC AGAA GGGU ACCAGAGAAACA 803 ACCCA GAU GAUGUG 865 X GUACAUUACCUGGUA 727 GUGGAA AGAA GCUC ACCAGAGAAACA 804 GAGCA GCU UUCCAC 866 X GUACAUUACCUGGUA 805 AUGGAA AGAA GCUG ACCAGAGAAACA 805 CAGCA GUC UUCCAU 867 10 X GUACAUUACCUGGUA 867 CAGAGC AGAA GCCA ACCAGAGAAACA 806 UGGCA GUA GCUCUG 868 X GUACAUUACCUGGUA 884 CACAGA AGAA GGGU ACCAGAGAAACA 807 ACCCA GUU UCUGUG 869 15 X GUACAUUACCUGGUA 918 UCCUGC AGAA GUUC ACCAGAGAAACA 808 GAACA GAU GCAGGA 870 X GUACAUUACCUGGUA 1025 GUCAUC AGAA GGGA ACCAGAGAAACA 809 UCCCA GAU GAUGAC 871 X GUACAUUACCUGGUA 20 1080 CCUGCA AGAA GCCA ACCAGAGAAACA 810 UGGCA GAU UGCAGG 872 X GUACAUUACCUGGUA 1107 UGUCUG AGAA GUUG ACCAGAGAAACA 811 CAACU GUA CAGACA 873 X GUACAUUACCUGGUA 1191 CCACAC AGAA GUGA ACCAGAGAAACA 812 UCACC GCU GUGUGG 874 25 X GUACAUUACCUGGUA 1205 GUAGCC AGAA GUAG ACCAGAGAAACA 813 CUACU GUU GGCUAC 875 X GUACAUUACCUGGUA 1273 CUUAGA AGAA GCUG ACCAGAGAAACA 814 CAGCA GCU UCUAAG 876 X GUACAUUACCUGGUA 30 1287 GUUGGA AGAA GUCU ACCAGAGAAACA 815 AGACA GCU UCCAAC 877 X GUACAUUACCUGGUA 1324 AUGACA AGAA GCAC ACCAGAGAAACA 816 GUGCU GUC UGUCAU 878 X GUACAUUACCUGGUA 1339 GACCGG AGAA GGAA ACCAGAGAAACA 817 UUCCG GUU CCGGUC 879 X GUACAUUACCUGGUA WO 99/50403 PCTIUS99/06507 90 Posi- Seq. I.D. Seq. tion RZ No. Substrate I.D. No. 1345 UUCUUA AGAA GGAA ACCAGAGAAACA 818 UUCCG GUC UAAGAA 880 X GUACAUUACCUGGUA 5 1380 UAAAGG AGAA GGUU ACCAGAGAAACA 819 AACCA GCU CCUUUA 881 X GUACAUUACCUGGUA 1409 AAUUUC AGAA GAGU ACCAGAGAAACA 820 ACUCA GAU GAAAUU 882 X GUACAUUACCUGGUA 1431 UGUUGG AGAA GAUG ACCAGAGAAACA 821 CAUCU GUA CCAACA 883 10 X GUACAUUACCUGGUA 1471 AGUGUA AGAA GUGG ACCAGAGAAACA 822 CCACG GCC UACACU 884 X GUACAUUACCUGGUA 1549 GGUGCC AGAA GUCC ACCAGAGAAACA 823 GGACA GCU GGCACC 885 15 X GUACAUUACCUGGUA 1642 GUCACA AGAA GAAC ACCAGAGAAACA 824 GUUCA GCC UGUGAC 886 X GUACAUUACCUGGUA 1691 UAAACC AGAA GACU ACCAGAGAAACA 825 AGUCA GAU GGUUUA 887 X GUACAUUACCUGGUA 20 1754 ACUCUG AGAA GCAU ACCAGAGAAACA 826 AUGCG GAU CAGAGU 888 X GUACAUUACCUGGUA 1784 GGCAGG AGAA GUGC ACCAGAGAAACA 827 GCACU GUC CCUGCC 889 X GUACAUUACCUGGUA 1840 UCUGCC AGAA GGGG ACCAGAGAAACA 828 CCCCG GCC GGCAGA 890 25 X GUACAUUACCUGGUA 1901 UGCAGA AGAA GAUG ACCAGAGAAACA 829 CAUCA GCU UCUGCA 891 X GUACAUUACCUGGUA 1915 GCCAAC AGAA GUCC ACCAGAGAAACA 830 GGACA GAU GUUGGC 892 X GUACAUUACCUGGUA 30 1927 CGGGAA AGAA GGGC ACCAGAGAAACA 831 GCCCA GAU UUCCCG 893 X GUACAUUACCUGGUA 1986 AGCCUG AGAA GGUA ACCAGAGAAACA 832 UACCC GCU CAGGCU 894 X GUACAUUACCUGGUA 2000 CUGCUG AGAA GAAA ACCAGAGAAACA 833 UUUCU GCC CAGCAG 895 X GUACAUUACCUGGUA I I WO 99/50403 PCT/US99/06507 91 Posi- Seq. I.D. Seq. tion RZ No. Substrate I.D. No. 2047 ACACCA AGAA GGGA ACCAGAGAAACA 834 UCCCA GUU UGGUGU 896 X GUACAUUACCUGGUA 5 2061 UCUGAA AGAA GCCC ACCAGAGAAACA 835 GGGCA GCU UUCAGA 897 X GUACAUUACCUGGUA 2068 GAUGGA AGAA GAAA ACCAGAGAAACA 836 UUUCA GAC UCCAUC 898 X GUACAUUACCUGGUA 10 2085 ACAUGG AGAA GAAG ACCAGAGAAACA 837 CUUCA GCU CCAUGU 899 X GUACAUUACCUGGUA 2129 GUAGGC AGAA GCAC ACCAGAGAAACA 838 GUGCU GCU GCCUAC 900 X GUACAUUACCUGGUA 2132 AGGGUA AGAA GCAG ACCAGAGAAACA 839 CUGCU GCC UACCCU 901 15 X GUACAUUACCUGGUA 2185 CCUGCA AGAA GUCC ACCAGAGAAACA 840 GGACA GAC UGCAGG 902 X GUACAUUACCUGGUA 2254 UGAUGA AGAA GCUG ACCAGAGAAACA 841 CAGCA GCC UCAUCA 903 X GUACAUUACCUGGUA 20 2320 CCUCA AGAA GGCC ACCAGAGAAACA 842 GGCCA GCC UGAGGU 904 X GUACAUUACCUGGUA 2344 AGCAUG AGAA GCAU ACCAGAGAAACA 843 AUGCU GUC CAUGCU 905 X GUACAUUACCUGGUA 2393 AGUUAG AGAA GGGA ACCAGAGAAACA 844 UCCCU GAU CUAACU 906 25 X GUACAUUACCUGGUA 2469 AAAACA AGAA GUGA ACCAGAGAAACA 845 UCACU GUU UGUUUU 907 X GUACAUUACCUGGUA 2567 CAGGGG AGAA GCCA ACCAGAGAAACA 846 UGGCU GUU CCCCUG 908 X GUACAUUACCUGGUA 30 2575 CAACAG AGAA GGGG ACCAGAGAAACA 847 CCCCU GCU CUGUUG 909 X GUACAUUACCUGGUA 2580 GGAGGC AGAA GAGC ACCAGAGAAACA 848 GCUCU GUU GCCUCC 910 X GUACAUUACCUGGUA WO 99/50403 PCT/US99/06507 92 TABLE V: HAMMERHEAD RIBOZYMES AND TARGET SITES FOR TIE Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 13 CAAGAAGG CUGAUGAG 911 UGUGCUGUU 1612 X CGAA ACAGCACA CCUUCUUG 5 14 GCAAGAAG CUGAUGAG 912 GUGCUGUUC 1613 X CGAA AACAGCAC CUUCUUGC 17 GAGGCAAG CUGAUGAG 913 CUGUUCCUU 1614 X CGAA AGGAACAG CUUGCCUC 18 AGAGGCAA CUGAUGAG 914 UGUUCCUUC 1615 10 X CGAA AAGGAACA UUGCCUCU 20 UUAGAGGC CUGAUGAG 915 UUCCUUCUU 1616 X CGAA AGAAGGAA GCCUCUAA 25 ACAAGUUA CUGAUGAG 916 UCUUGCCUC 1617 15 X CGAA AGGCAAGA UAACUUGU 27 UUACAAGU CUGAUGAG 917 UUGCCUCUA 1618 X CGAA AGAGGCAA ACUUGUAA 31 UUGUUUAC CUGAUGAG 918 CUCUAACUU 1619 X CGAA AGUUAGAG GUAAACAA 20 34 GUCUUGUU CUGAUGAG 919 UAACUUGUA 1620 X CGAA ACAAGUUA AACAAGAC 45 CGUCCUAG CUGAUGAG 920 CAAGACGUA 1621 X CGAA ACGUCUUG CUAGGACG 48 CAUCGUCC CUGAUGAG 921 GACGUACUA 1622 25 X CGAA AGUACGUC GGACGAUG 59 CUUUCCAU CUGAUGAG 922 ACGAUGCUA 1623 X CGAA AGCAUCGU AUGGAAAG 69 CGGUUUGU CUGAUGAG 923 UGGAAAGUC 1624 X CGAA ACUUUCCA ACAAACCG 30 84 CUUUCAAA CUGAUGAG 924 CGCUGGGUU 1625 X CGAA ACCCAGCG UUUGAAAG 85 CCUUUCAA CUGAUGAG 925 GCUGGGUUU 1626 X CGAA AACCCAGC UUGAAAGG WO 99/50403 PCT/US99/06507 93 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 86 UCCUUUCA CUGAUGAG 926 CUGGGUUUU 1627 X CGAA AAACCCAG UGAAAGGA 5 87 AUCCUUUC CUGAUGAG 927 UGGGUUUUU 1628 X CGAA AAAACCCA GAAAGGAU 96 GUCCCAAG CUGAUGAG 928 GAAAGGAUC 1629 X CGAA AUCCUUUC CUUGGGAC 99 GAGGUCCC CUGAUGAG 929 AGGAUCCUU 1630 10 X CGAA AGGAUCCU GGGACCUC 107 AUGUGCAU CUGAUGAG 930 UGGGACCUC 1631 X CGAA AGGUCCCA AUGCACAU 116 UUUCCACA CUGAUGAG 931 AUGCACAUU 1632 X CGAA AUGUGCAU UGUGGAAA 15 117 GUUUCCAC CUGAUGAG 932 UGCACAUUU 1633 X CGAA AAUGUGCA GUGGAAAC 139 CUUCCCCA CUGAUGAG 933 GGAGAGAUU 1634 X CGAA AUCUCUCC UGGGGAAG 140 GCUUCCCC CUGAUGAG 934 GAGAGAUUU 1635 20 X CGAA AAUCUCUC GGGGAAGC 156 UGGCUAAA CUGAUGAG 935 CAUGGACUC 1636 X CGAA AGUCCAUG UUUAGCCA 158 GCUGGCUA CUGAUGAG 936 UGGACUCUU 1637 X CGAA AGAGUCCA UAGCCAGC 25 159 AGCUGGCU CUGAUGAG 937 GGACUCUUU 1638 X CGAA AAGAGUCC AGCCAGCU 160 AAGCUGGC CUGAUGAG 938 GACUCUUUA 1639 X CGAA AAAGAGUC GCCAGCUU 168 AGAGAACU CUGAUGAG 939 AGCCAGCUU 1640 30 X CGAA AGCUGGCU AGUUCUCU 169 CAGAGAAC CUGAUGAG 940 GCCAGCUUA 1641 X CGAA AAGCUGGC GUUCUCUG 172 CCACAGAG CUGAUGAG 941 AGCUUAGUU 1642 X CGAA ACUAAGCU CUCUGUGG WO 99/50403 PCT/US99/06507 94 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 173 UCCACAGA CUGAUGAG 942 GCUUAGUUC 1643 X CGAA AACUAAGC UCUGUGGA 5 175 ACUCCACA CUGAUGAG 943 UUAGUUCUC 1644 X CGAA AGAACUAA UGUGGAGU 184 AGCAAGCU CUGAUGAG 944 UGUGGAGUC 1645 X CGAA ACUCCACA AGCUUGCU 189 AAAGGAGC CUGAUGAG 945 AGUCAGCUU 1646 10 X CGAA AGCUGACU GCUCCUUU 193 CCAGAAAG CUGAUGAG 946 AGCUUGCUC 1647 X CGAA AGCAAGCU CUUUCUGG 196 GUUCCAGA CUGAUGAG 947 UUGCUCCUU 1648 X CGAA AGGAGCAA UCUGGAAC 15 197 AGUUCCAG CUGAUGAG 948 UGCUCCUUU 1649 X CGAA AAGGAGCA CUGGAACU 198 CAGUUCCA CUGAUGAG 949 GCUCCUUUC 1650 X CGAA AAAGGAGC UGGAACUG 225 UCAAGAUC CUGAUGAG 950 CAUGGACUU 1651 20 X CGAA AGUCCAUG GAUCUUGA 229 UUGAUCAA CUGAUGAG 951 GACUUGAUC 1652 X CGAA AUCAAGUC UUGAUCAA 231 AAUUGAUC CUGAUGAG 952 CUUGAUCUU 1653 X CGAA AGAUCAAG GAUCAAUU 25 235 AGGGAAUU CUGAUGAG 953 AUCUUGAUC 1654 X CGAA AUCAAGAU AAUUCCCU 239 AGGUAGGG CUGAUGAG 954 UGAUCAAUU 1655 X CGAA AUUGAUCA CCCUACCU 240 GAGGUAGG CUGAUGAG 955 GAUCAAUUC 1656 30 X CGAA AAUUGAUC CCUACCUC 244 ACAAGAGG CUGAUGAG 956 AAUUCCCUA 1657 X CGAA AGGGAAUU CCUCUUGU 248 AGAUACAA CUGAUGAG 957 CCCUACCUC 1658 X CGAA AGGUAGGG UUGUAUCU WO 99/50403 PCTIUS99/06507 95 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 250 UCAGAUAC CUGAUGAG 958 CUACCUCUU 1659 X CGAA AGAGGUAG GUAUCUGA 5 253 GCAUCAGA CUGAUGAG 959 CCUCUUGUA 1660 X CGAA ACAAGAGG UCUGAUGC 255 CAGCAUCA CUGAUGAG 960 UCUUGUAUC 1661 X CGAA AUACAAGA UGAUGCUG 270 AGGUGAGA CUGAUGAG 961 UGAAACAUC 1662 10 X CGAA AUGUUUCA UCUCACCU 272 GCAGGUGA CUGAUGAG 962 AAACAUCUC 1663 X CGAA AGAUGUUU UCACCUGC 274 AUGCAGGU CUGAUGAG 963 ACAUCUCUC 1664 X CGAA AGAGAUGU ACCUGCAU 15 283 CCAGAGGC CUGAUGAG 964 ACCUGCAUU 1665 X CGAA AUGCAGGU GCCUCUGG 288 GCCACCCA CUGAUGAG 965 CAUUGCCUC 1666 X CGAA AGGCAAUG UGGGUGGC 313 CCUAUGGU CUGAUGAG 966 GAGCCCAUC 1667 20 X CGAA AUGGGCUC ACCAUAGG 319 UCCCUUCC CUGAUGAG 967 AUCACCAUA 1668 X CGAA AUGGUGAU GGAAGGGA 330 AGGCUUCA CUGAUGAG 968 AAGGGACUU 1669 X CGAA AGUCCCUU UGAAGCCU 25 331 AAGGCUUC CUGAUGAG 969 AGGGACUUU 1670 X CGAA AAGUCCCU GAAGCCUU 339 GGUUCAUU CUGAUGAG 970 UGAAGCCUU 1671 X CGAA AGGCUUCA AAUGAACC 340 UGGUUCAU CUGAUGAG 971 GAAGCCUUA 1672 30 X CGAA AAGGCUUC AUGAACCA 359 UUCCAGCG CUGAUGAG 972 ACCAGGAUC 1673 X CGAA AUCCUGGU CGCUGGAA 370 UCUUGAGU CUGAUGAG 973 CUGGAAGUU 1674 X CGAA ACUUCCAG ACUCAAGA WO 99/50403 PCTIUS99/06507 96 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 371 AUCUUGAG CUGAUGAG 974 UGGAAGUUA 1675 X CGAA AACUUCCA CUCAAGAU 5 374 CACAUCUU CUGAUGAG 975 AAGUUACUC 1676 X CGAA AGUAACUU AAGAUGUG 398 AACUUUUU CUGAUGAG 976 AAUGGGCUA 1677 X CGAA AGCCCAUU AAAAAGUU 406 UUCCAAAC CUGAUGAG 977 AAAAAAGUU 1678 10 X CGAA ACUUUUUU GUUUGGAA 409 CUCUUCCA CUGAUGAG 978 AAAGUUGUU 1679 X CGAA ACAACUUU UGGAAGAG 410 UCUCUUCC CUGAUGAG 979 AAGUUGUUU 1680 X CGAA AACAACUU GGAAGAGA 15 428 GAUCUUAC CUGAUGAG 980 AAAAGGCUA 1681 X CGAA AGCCUUUU GUAAGAUC 431 AUUGAUCU CUGAUGAG 981 AGGCUAGUA 1682 X CGAA ACUAGCCU AGAUCAAU 436 GCACCAUU CUGAUGAG 982 AGUAAGAUC 1683 20 X CGAA AUCUUACU AAUGGUGC 446 ACAGAAAU CUGAUGAG 983 AUGGUGCUU 1684 X CGAA AGCACCAU AUUUCUGU 447 CACAGAAA CUGAUGAG 984 UGGUGCUUA 1685 X CGAA AAGCACCA UUUCUGUG 25 449 UUCACAGA CUGAUGAG 985 GUGCUUAUU 1686 X CGAA AUAAGCAC UCUGUGAA 450 CUUCACAG CUGAUGAG 986 UGCUUAUUU 1687 X CGAA AAUAAGCA CUGUGAAG 451 CCUUCACA CUGAUGAG 987 GCUUAUUUC 1688 30 X CGAA AAAUAAGC UGUGAAGG 466 UCUCCUCG CUGAUGAG 988 GGGCGAGUU 1689 X CGAA ACUCGCCC CGAGGAGA 467 CUCUCCUC CUGAUGAG 989 GGCGAGUUC 1690 X CGAA AACUCGCC GAGGAGAG WO 99/50403 PCT/US99/06507 97 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 481 CGUAUCCU CUGAUGAG 990 GAGGCAAUC 1691 X CGAA AUUGCCUC AGGAUACG 5 487 AUGGUUCG CUGAUGAG 991 AUCAGGAUA 1692 X CGAA AUCCUGAU CGAACCAU 506 AGCUUGUU CUGAUGAG 992 AGAUGCGUC 1693 X CGAA ACGCAUCU AACAAGCU 515 UAGGAAGG CUGAUGAG 993 AACAAGCUU 1694 10 X CGAA AGCUUGUU CCUUCCUA 516 GUAGGAAG CUGAUGAG 994 ACAAGCUUC 1695 X CGAA AAGCUUGU CUUCCUAC 519 CUGGUAGG CUGAUGAG 995 AGCUUCCUU 1696 X CGAA AGGAAGCU CCUACCAG 15 520 GCUGGUAG CUGAUGAG 996 GCUUCCUUC 1697 X CGAA AAGGAAGC CUACCAGC 523 GUAGCUGG CUGAUGAG 997 UCCUUCCUA 1698 X CGAA AGGAAGGA CCAGCUAC 530 AGUUAAAG CUGAUGAG 998 UACCAGCUA 1699 20 X CGAA AGCUGGUA CUUUAACU 533 CAUAGUUA CUGAUGAG 999 CAGCUACUU 1700 X CGAA AGUAGCUG UAACUAUG 534 UCAUAGUU CUGAUGAG 1000 AGCUACUUU 1701 X CGAA AAGUAGCU AACUAUGA 25 535 GUCAUAGU CUGAUGAG 1001 GCUACUUUA 1702 X CGAA AAAGUAGC ACUAUGAC 539 CACAGUCA CUGAUGAG 1002 CUUUAACUA 1703 X CGAA AGUUAAAG UGACUGUG 560 GUUCACGU CUGAUGAG 1003 AGGGAGAUA 1704 30 X CGAA AUCUCCCU ACGUGAAC 571 UUGAAAGA CUGAUGAG 1004 GUGAACAUA 1705 X CGAA AUGUUCAC UCUUUCAA 573 UUUUGAAA CUGAUGAG 1005 GAACAUAUC 1706 X CGAA AUAUGUUC UUUCAAAA WO 99/50403 PCT/US99/06507 98 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 575 CUUUUUGA CUGAUGAG 1006 ACAUAUCUU 1707 X CGAA AGAUAUGU UCAAAAAG 5 576 CCUUUUUG CUGAUGAG 1007 CAUAUCUUU 1708 X CGAA AAGAUAUG CAAAAAGG 577 ACCUUUUU CUGAUGAG 1008 AUAUCUUUC 1709 X CGAA AAAGAUAU AAAAAGGU 586 UUAAUCAA CUGAUGAG 1009 AAAAAGGUA 1710 10 X CGAA ACCUUUUU UUGAUUAA 588 CUUUAAUC CUGAUGAG 1010 AAAGGUAUU 1711 X CGAA AUACCUUU GAUUAAAG 592 UCUUCUUU CUGAUGAG 1011 GUAUUGAUU 1712 X CGAA AUCAAUAC AAAGAAGA 15 593 UUCUUCUU CUGAUGAG 1012 UAUUGAUUA 1713 X CGAA AAUCAAUA AAGAAGAA 613 UUUUUGUA CUGAUGAG 1013 GCAGUGAUU 1714 X CGAA AUCACUGC UACAAAAA 614 AUUUUUGU CUGAUGAG 1014 CAGUGAUUU 1715 20 X CGAA AAUCACUG ACAAAAAU 615 CAUUUUUG CUGAUGAG 1015 AGUGAUUUA 1716 X CGAA AAAUCACU CAAAAAUG 626 GAUGAAGG CUGAUGAG 1016 AAAAUGGUU 1717 X CGAA ACCAUUUU CCUUCAUC 25 627 GGAUGAAG CUGAUGAG 1017 AAAUGGUUC 1718 X CGAA AACCAUUU CUUCAUCC 630 AAUGGAUG CUGAUGAG 1018 UGGUUCCUU 1719 X CGAA AGGAACCA CAUCCAUU 631 GAAUGGAU CUGAUGAG 1019 GGUUCCUUC 1720 30 X CGAA AAGGAACC AUCCAUUC 634 ACUGAAUG CUGAUGAG 1020 UCCUUCAUC 1721 X CGAA AUGAAGGA CAUUCAGU 638 GGGCACUG CUGAUGAG 1021 UCAUCCAUU 1722 X CGAA AUGGAUGA CAGUGCCC WO 99/50403 PCTIUS99/06507 99 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 639 GGGGCACU CUGAUGAG 1022 CAUCCAUUC 1723 X CGAA AAUGGAUG AGUGCCCC 5 658 AUAUCAGG CUGAUGAG 1023 CAUGAAGUA 1724 X CGAA ACUUCAUG CCUGAUAU 665 UUCUAGAA CUGAUGAG 1024 UACCUGAUA 1725 X CGAA AUCAGGUA UUCUAGAA 667 ACUUCUAG CUGAUGAG 1025 CCUGAUAUU 1726 10 X CGAA AUAUCAGG CUAGAAGU 668 UACUUCUA CUGAUGAG 1026 CUGAUAUUC 1727 X CGAA AAUAUCAG UAGAAGUA 670 UGUACUUC CUGAUGAG 1027 GAUAUUCUA 1728 X CGAA AGAAUAUC GAAGUACA 15 676 GGCAGGUG CUGAUGAG 1028 CUAGAAGUA 1729 X CGAA ACUUCUAG CACCUGCC 686 CUGAGCAU CUGAUGAG 1029 ACCUGCCUC 1730 X CGAA AGGCAGGU AUGCUCAG 692 CUGGGGCU CUGAUGAG 1030 CUCAUGCUC 1731 20 X CGAA AGCAUGAG AGCCCCAG 714 UGGCCGAG CUGAUGAG 1031 UGGAGUGUA 1732 X CGAA ACACUCCA CUCGGCCA 717 ACCUGGCC CUGAUGAG 1032 AGUGUACUC 1733 X CGAA AGUACACU GGCCAGGU 25 726 CUCCUAUA CUGAUGAG 1033 GGCCAGGUA 1734 X CGAA ACCUGGCC UAUAGGAG 728 UCCUCCUA CUGAUGAG 1034 CCAGGUAUA 1735 X CGAA AUACCUGG UAGGAGGA 730 UUUCCUCC CUGAUGAG 1035 AGGUAUAUA 1736 30 X CGAA AUAUACCU GGAGGAAA 742 GAGGUGAA CUGAUGAG 1036 GGAAACCUC 1737 X CGAA AGGUUUCC UUCACCUC 744 CCGAGGUG CUGAUGAG 1037 AAACCUCUU 1738 X CGAA AGAGGUUU CACCUCGG WO 99/50403 PCT/US99/06507 100 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 745 GCCGAGGU CUGAUGAG 1038 AACCUCUUC 1739 X CGAA AAGAGGUU ACCUCGGC 5 750 UGAAGGCC CUGAUGAG 1039 CUUCACCUC 1740 X CGAA AGGUGAAG GGCCUUCA 756 GCCUGGUG CUGAUGAG 1040 CUCGGCCUU 1741 X CGAA AGGCCGAG CACCAGGC 757 AGCCUGGU CUGAUGAG 1041 UCGGCCUUC 1742 10 X CGAA AAGGCCGA ACCAGGCU 769 CUCCGGAC CUGAUGAG 1042 AGGCUGAUA 1743 X CGAA AUCAGCCU GUCCGGAG 772 CAUCUCCG CUGAUGAG 1043 CUGAUAGUC 1744 X CGAA ACUAUCAG CGGAGAUG 15 815 AGUACAGA CUGAUGAG 1044 GCAACCAUC 1745 X CGAA AUGGUUGC UCUGUACU 817 GCAGUACA CUGAUGAG 1045 AACCAUCUC 1746 X CGAA AGAUGGUU UGUACUGC 821 ACAAGCAG CUGAUGAG 1046 AUCUCUGUA 1747 20 X CGAA ACAGAGAU CUGCUUGU 827 GUUCAUAC CUGAUGAG 1047 GUACUGCUU 1748 X CGAA AGCAGUAC GUAUGAAC 830 AUUGUUCA CUGAUGAG 1048 CUGCUUGUA 1749 X CGAA ACAAGCAG UGAACAAU 25 844 UCAUGGCA CUGAUGAG 1049 AAUGGUGUC 1750 X CGAA ACACCAUU UGCCAUGA 857 UUCUCCAG CUGAUGAG 1050 AUGAAGAUA 1751 X CGAA AUCUUCAU CUGGAGAA 871 GGAGGGCA CUGAUGAG 1051 GAAUGCAUU 1752 30 X CGAA AUGCAUUC UGCCCUCC 872 AGGAGGGC CUGAUGAG 1052 AAUGCAUUU 1753 X CGAA AAUGCAUU GCCCUCCU 878 AAACCCAG CUGAUGAG 1053 UUUGCCCUC 1754 X CGAA AGGGCAAA CUGGGUUU WO 99/50403 PCT/US99/06507 101 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 885 UUCCCAUA CUGAUGAG 1054 UCCUGGGUU 1755 X CGAA ACCCAGGA UAUGGGAA 5 886 CUUCCCAU CUGAUGAG 1055 CCUGGGUUU 1756 X CGAA AACCCAGG AUGGGAAG 887 CCUUCCCA CUGAUGAG 1056 CUGGGUUUA 1757 X CGAA AAACCCAG UGGGAAGG 911 CAGUUCAC CUGAUGAG 1057 AGAAGGCUU 1758 10 X CGAA AGCCUUCU GUGAACUG 927 UUCUGCCA CUGAUGAG 1058 GCACACGUU 1759 X CGAA ACGUGUGC UGGCAGAA 928 GUUCUGCC CUGAUGAG 1059 CACACGUUU 1760 X CGAA AACGUGUG GGCAGAAC 15 938 UUCUUUAC CUGAUGAG 1060 GCAGAACUU 1761 X CGAA AGUUCUGC GUAAAGAA 941 CCUUUCUU CUGAUGAG 1061 GAACUUGUA 1762 X CGAA ACAAGUUC AAGAAAGG 975 ACACAUAA CUGAUGAG 1062 AUGCAAGUC 1763 20 X CGAA ACUUGCAU UUAUGUGU 977 GAACACAU CUGAUGAG 1063 GCAAGUCUU 1764 X CGAA AGACUUGC AUGUGUUC 978 AGAACACA CUGAUGAG 1064 CAAGUCUUA 1765 X CGAA AAGACUUG UGUGUUCU 25 984 GGAGACAG CUGAUGAG 1065 UUAUGUGUU 1766 X CGAA ACACAUAA CUGUCUCC 985 GGGAGACA CUGAUGAG 1066 UAUGUGUUC 1767 X CGAA AACACAUA UGUCUCCC 989 GUCAGGGA CUGAUGAG 1067 UGUUCUGUC 1768 30 X CGAA ACAGAACA UCCCUGAC 991 GGGUCAGG CUGAUGAG 1068 UUCUGUCUC 1769 X CGAA AGACAGAA CCUGACCC 1002 AACACCCA CUGAUGAG 1069 UGACCCCUA 1770 X CGAA AGGGGUCA UGGGUGUU WO 99/50403 PCT/US99/06507 102 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1010 GGCACAGG CUGAUGAG 1070 AUGGGUGUU 1771 X CGAA ACACCCAU CCUGUGCC 5 1011 UGGCACAG CUGAUGAG 1071 UGGGUGUUC 1772 X CGAA AACACCCA CUGUGCCA 1034 GCACUGCA CUGAUGAG 1072 GGAAGGGUC 1773 X CGAA ACCCUUCC UGCAGUGC 1064 CCCGUAAA CUGAUGAG 1073 ACCCUGGUU 1774 10 X CGAA ACCAGGGU UUUACGGG 1065 GCCCGUAA CUGAUGAG 1074 CCCUGGUUU 1775 X CGAA AACCAGGG UUACGGGC 1066 GGCCCGUA CUGAUGAG 1075 CCUGGUUUU 1776 X CGAA AAACCAGG UACGGGCC 15 1067 UGGCCCGU CUGAUGAG 1076 CUGGUUUUU 1777 X CGAA AAAACCAG ACGGGCCA 1068 CUGGCCCG CUGAUGAG 1077 UGGUUUUUA 1778 X CGAA AAAAACCA CGGGCCAG 1079 AAGCUUAC CUGAUGAG 1078 GGCCAGAUU 1779 20 X CGAA AUCUGGCC GUAAGCUU 1082 CCUAAGCU CUGAUGAG 1079 CAGAUUGUA 1780 X CGAA ACAAUCUG AGCUUAGG 1087 CUGCACCU CUGAUGAG 1080 UGUAAGCUU 1781 X CGAA AGCUUACA AGGUGCAG 25 1088 GCUGCACC CUGAUGAG 1081 GUAAGCUUA 1782 X CGAA AAGCUUAC GGUGCAGC 1121 UUGGAAGC CUGAUGAG 1082 UGUGUGAUC 1783 X CGAA AUCACACA GCUUCCAA 1125 AUCCUUGG CUGAUGAG 1083 UGAUCGCUU 1784 30 X CGAA AGCGAUCA CCAAGGAU 1126 CAUCCUUG CUGAUGAG 1084 GAUCGCUUC 1785 X CGAA AAGCGAUC CAAGGAUG 1136 AGAGCAGA CUGAUGAG 1085 AAGGAUGUC 1786 X CGAA ACAUCCUU UCUGCUCU WO 99/50403 PCTIUS99/06507 103 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1138 GGAGAGCA CUGAUGAG 1086 GGAUGUCUC 1787 X CGAA AGACAUCC UGCUCUCC 5 1143 AUCCUGGA CUGAUGAG 1087 UCUCUGCUC 1788 X CGAA AGCAGAGA UCCAGGAU 1145 CCAUCCUG CUGAUGAG 1088 UCUGCUCUC 1789 X CGAA AGAGCAGA CAGGAUGG 1162 UCACACUG CUGAUGAG 1089 CAGGGGCUC 1790 10 X CGAA AGCCCCUG CAGUGUGA 1183 AUCCUCGG CUGAUGAG 1090 GAAGGCAUA 1791 X CGAA AUGCCUUC CCGAGGAU 1204 AAAUCCAC CUGAUGAG 1091 CCAAAGAUA 1792 X CGAA AUCUUUGG GUGGAUUU 15 1211 AUCUGGCA CUGAUGAG 1092 UAGUGGAUU 1793 X CGAA AUCCACUA UGCCAGAU 1212 GAUCUGGC CUGAUGAG 1093 AGUGGAUUU 1794 X CGAA AAUCCACU GCCAGAUC 1220 UUCUAUAU CUGAUGAG 1094 UGCCAGAUC 1795 20 X CGAA AUCUGGCA AUAUAGAA 1223 UACUUCUA CUGAUGAG 1095 CAGAUCAUA 1796 X CGAA AUGAUCUG UAGAAGUA 1225 UUUACUUC CUGAUGAG 1096 GAUCAUAUA 1797 X CGAA AUAUGAUC GAAGUAAA 25 1231 CCACUGUU CUGAUGAG 1097 AUAGAAGUA 1798 X CGAA ACUUCUAU AACAGUGG 1241 AUUAAAUU CUGAUGAG 1098 ACAGUGGUA 1799 X CGAA ACCACUGU AAUUUAAU 1245 UGGGAUUA CUGAUGAG 1099 UGGUAAAUU 1800 30 X CGAA AUUUACCA UAAUCCCA 1246 AUGGGAUU CUGAUGAG 1100 GGUAAAUUU 1801 X CGAA AAUUUACC AAUCCCAU 1247 AAUGGGAU CUGAUGAG 1101 GUAAAUUUA 1802 X CGAA AAAUUUAC AUCCCAUU WO 99/50403 PCT/US99/06507 104 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1250 GCAAAUGG CUGAUGAG 1102 AAUUUAAUC 1803 X CGAA AUUAAAUU CCAUUUGC 5 1255 GCUUUGCA CUGAUGAG 1103 AAUCCCAUU 1804 X CGAA AUGGGAUU UGCAAAGC 1256 AGCUUUGC CUGAUGAG 1104 AUCCCAUUU 1805 X CGAA AAUGGGAU GCAAAGCU 1265 CCAGCCAG CUGAUGAG 1105 GCAAAGCUU 1806 10 X CGAA AGCUUUGC CUGGCUGG 1266 GCCAGCCA CUGAUGAG 1106 CAAAGCUUC 1807 X CGAA AAGCUUUG UGGCUGGC 1279 UUAGUAGG CUGAUGAG 1107 UGGCCGCUA 1808 X CGAA AGCGGCCA CCUACUAA 15 1283 UUCAUUAG CUGAUGAG 1108 CGCUACCUA 1809 X CGAA AGGUAGCG CUAAUGAA 1286 UUCUUCAU CUGAUGAG 1109 UACCUACUA 1810 X CGAA AGUAGGUA AUGAAGAA 1327 UUUGGAUG CUGAUGAG 1110 ACAGUGCUC 1811 20 X CGAA AGCACUGU CAUCCAAA 1331 GUCUUUUG CUGAUGAG 1111 UGCUCCAUC 1812 X CGAA AUGGAGCA CAAAAGAC 1341 UAUGGUUA CUGAUGAG 1112 AAAAGACUU 1813 X CGAA AGUCUUUU UAACCAUA 25 1342 GUAUGGUU CUGAUGAG 1113 AAAGACUUU 1814 X CGAA AAGUCUUU AACCAUAC 1343 CGUAUGGU CUGAUGAG 1114 AAGACUUUA 1815 X CGAA AAAGUCUU ACCAUACG 1349 AUGAUCCG CUGAUGAG 1115 UUAACCAUA 1816 30 X CGAA AUGGUUAA CGGAUCAU 1355 UGAGAAAU CUGAUGAG 1116 AUACGGAUC 1817 X CGAA AUCCGUAU AUUUCUCA 1358 UACUGAGA CUGAUGAG 1117 CGGAUCAUU 1818 X CGAA AUGAUCCG UCUCAGUA WO 99/50403 PCTIUS99/06507 105 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1359 CUACUGAG CUGAUGAG 1118 GGAUCAUUU 1819 X CGAA AAUGAUCC CUCAGUAG 5 1360 GCUACUGA CUGAUGAG 1119 GAUCAUUUC 1820 X CGAA AAAUGAUC UCAGUAGC 1362 UGGCUACU CUGAUGAG 1120 UCAUUUCUC 1821 X CGAA AGAAAUGA AGUAGCCA 1366 AAUAUGGC CUGAUGAG 1121 UUCUCAGUA 1822 10 X CGAA ACUGAGAA GCCAUAUU 1372 AUGGUGAA CUGAUGAG 1122 GUAGCCAUA 1823 X CGAA AUGGCUAC UUCACCAU 1374 GGAUGGUG CUGAUGAG 1123 AGCCAUAUU 1824 X CGAA AUAUGGCU CACCAUCC 15 1375 UGGAUGGU CUGAUGAG 1124 GCCAUAUUC 1825 X CGAA AAUAUGGC ACCAUCCA 1381 AUCCGGUG CUGAUGAG 1125 UUCACCAUC 1826 X CGAA AUGGUGAA CACCGGAU 1390 GGGGGGAG CUGAUGAG 1126 CACCGGAUC 1827 20 X CGAA AUCCGGUG CUCCCCCC 1393 UCAGGGGG CUGAUGAG 1127 CGGAUCCUC 1828 X CGAA AGGAUCCG CCCCCUGA 1404 AAACUCCU CUGAUGAG 1128 CCCUGACUC 1829 X CGAA AGUCAGGG AGGAGUUU 25 1411 CAGACCCA CUGAUGAG 1129 UCAGGAGUU 1830 X CGAA ACUCCUGA UGGGUCUG 1412 GCAGACCC CUGAUGAG 1130 CAGGAGUUU 1831 X CGAA AACUCCUG GGGUCUGC 1417 ACACUGCA CUGAUGAG 1131 GUUUGGGUC 1832 30 X CGAA ACCCAAAC UGCAGUGU 1458 AAAUGUUG CUGAUGAG 1132 AAAGCCCUU 1833 X CGAA AGGGCUUU CAACAUUU 1459 GAAAUGUU CUGAUGAG 1133 AAGCCCUUC 1834 X CGAA AAGGGCUU AACAUUUC WO 99/50403 PCT/US99/06507 106 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1465 UUAACAGA CUGAUGAG 1134 UUCAACAUU 1835 X CGAA AUGUUGAA UCUGUUAA 5 1466 UUUAACAG CUGAUGAG 1135 UCAACAUUU 1836 X CGAA AAUGUUGA CUGUUAAA 1467 CUUUAACA CUGAUGAG 1136 CAACAUUUC 1837 X CGAA AAAUGUUG UGUUAAAG 1471 AGAACUUU CUGAUGAG 1137 AUUUCUGUU 1838 10 X CGAA ACAGAAAU AAAGUUCU 1472 AAGAACUU CUGAUGAG 1138 UUUCUGUUA 1839 X CGAA AACAGAAA AAGUUCUU 1477 UUUGGAAG CUGAUGAG 1139 GUUAAAGUU 1840 X CGAA ACUUUAAC CUUCCAAA 15 1478 CUUUGGAA CUGAUGAG 1140 UUAAAGUUC 1841 X CGAA AACUUUAA UUCCAAAG 1480 GGCUUUGG CUGAUGAG 1141 AAAGUUCUU 1842 X CGAA AGAACUUU CCAAAGCC 1481 GGGCUUUG CUGAUGAG 1142 AAGUUCUUC 1843 20 X CGAA AAGAACUU CAAAGCCC 1510 CCAGUGUC CUGAUGAG 1143 AACGUGAUU 1844 X CGAA AUCACGUU GACACUGG 1523 AGCAAAGU CUGAUGAG 1144 CUGGACAUA 1845 X CGAA AUGUCCAG ACUUUGCU 25 1527 UGACAGCA CUGAUGAG 1145 ACAUAACUU 1846 X CGAA AGUUAUGU UGCUGUCA 1528 AUGACAGC CUGAUGAG 1146 CAUAACUUU 1847 X CGAA AAGUUAUG GCUGUCAU 1534 AUGUUGAU CUGAUGAG 1147 UUUGCUGUC 1848 30 X CGAA ACAGCAAA AUCAACAU 1537 CUGAUGUU CUGAUGAG 1148 GCUGUCAUC 1849 X CGAA AUGACAGC AACAUCAG 1543 UCAGAGCU CUGAUGAG 1149 AUCAACAUC 1850 X CGAA AUGUUGAU AGCUCUGA WO 99/50403 PCT/US99/06507 107 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1548 AAGGCUCA CUGAUGAG 1150 CAUCAGCUC 1851 X CGAA AGCUGAUG UGAGCCUU 5 1556 CCCAAAGU CUGAUGAG 1151 CUGAGCCUU 1852 X CGAA AGGCUCAG ACUUUGGG 1557 CCCCAAAG CUGAUGAG 1152 UGAGCCUUA 1853 X CGAA AAGGCUCA CUUUGGGG 1560 CAUCCCCA CUGAUGAG 1153 GCCUUACUU 1854 10 X CGAA AGUAAGGC UGGGGAUG 1561 CCAUCCCC CUGAUGAG 1154 CCUUACUUU 1855 X CGAA AAGUAAGG GGGGAUGG 1576 UUGGAUUU CUGAUGAG 1155 GGACCAAUC 1856 X CGAA AUUGGUCC AAAUCCAA 15 1581 GCUUCUUG CUGAUGAG 1156 AAUCAAAUC 1857 X CGAA AUUUGAUU CAAGAAGC 1591 UUGUAUAG CUGAUGAG 1157 AAGAAGCUU 1858 X CGAA AGCUUCUU CUAUACAA 1592 UUUGUAUA CUGAUGAG 1158 AGAAGCUUC 1859 20 X CGAA AAGCUUCU UAUACAAA 1594 GGUUUGUA CUGAUGAG 1159 AAGCUUCUA 1860 X CGAA AGAAGCUU UACAAACC 1596 CGGGUUUG CUGAUGAG 1160 GCUUCUAUA 1861 X CGAA AUAGAAGC CAAACCCG 25 1606 UAGUGAUU CUGAUGAG 1161 AAACCCGUU 1862 X CGAA ACGGGUUU AAUCACUA 1607 AUAGUGAU CUGAUGAG 1162 AACCCGUUA 1863 X CGAA AACGGGUU AUCACUAU 1610 CUCAUAGU CUGAUGAG 1163 CCGUUAAUC 1864 30 X CGAA AUUAACGG ACUAUGAG 1614 AAGCCUCA CUGAUGAG 1164 UAAUCACUA 1865 X CGAA AGUGAUUA UGAGGCUU 1622 AUGUUGCC CUGAUGAG 1165 AUGAGGCUU 1866 X CGAA AGCCUCAU GGCAACAU WO 99/50403 PCTIUS99/06507 108 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1631 CACUUGAA CUGAUGAG 1166 GGCAACAUA 1867 X CGAA AUGUUGCC UUCAAGUG 5 1633 GUCACUUG CUGAUGAG 1167 CAACAUAUU 1868 X CGAA AUAUGUUG CAAGUGAC 1634 UGUCACUU CUGAUGAG 1168 AACAUAUUC 1869 X CGAA AAUAUGUU AAGUGACA 1651 AGUGUAAC CUGAUGAG 1169 AAUGAGAUU 1870 10 X CGAA AUCUCAUU GUUACACU 1654 UUGAGUGU CUGAUGAG 1170 GAGAUUGUU 1871 X CGAA ACAAUCUC ACACUCAA 1655 GUUGAGUG CUGAUGAG 1171 AGAUUGUUA 1872 X CGAA AACAAUCU CACUCAAC 15 1660 AAAUAGUU CUGAUGAG 1172 GUUACACUC 1873 X CGAA AGUGUAAC AACUAUUU 1665 GUUCCAAA CUGAUGAG 1173 ACUCAACUA 1874 X CGAA AGUUGAGU UUUGGAAC 1667 AGGUUCCA CUGAUGAG 1174 UCAACUAUU 1875 20 X CGAA AUAGUUGA UGGAACCU 1668 GAGGUUCC CUGAUGAG 1175 CAACUAUUU 1876 X CGAA AAUAGUUG GGAACCUC 1676 UUCUGUCC CUGAUGAG 1176 UGGAACCUC 1877 X CGAA AGGUUCCA GGACAGAA 25 1686 AGAGUUCA CUGAUGAG 1177 GACAGAAUA 1878 X CGAA AUUCUGUC UGAACUCU 1693 UGCACACA CUGAUGAG 1178 UAUGAACUC 1879 X CGAA AGUUCAUA UGUGUGCA 1708 CCACGACG CUGAUGAG 1179 CAACUGGUC 1880 30 X CGAA ACCAGUUG CGUCGUGG 1712 CUCUCCAC CUGAUGAG 1180 UGGUCCGUC 1881 X CGAA ACGGACCA GUGGAGAG 1736 AGGUCCAG CUGAUGAG 1181 AAGGGCAUC 1882 X CGAA AUGCCCUU CUGGACCU WO 99/50403 PCT/US99/06507 109 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1755 CUGUUGUG CUGAUGAG 1182 GAGACGCUU 1883 X CGAA AGCGUCUC CACAACAG 5 1756 GCUGUUGU CUGAUGAG 1183 AGACGCUUC 1884 X CGAA AAGCGUCU ACAACAGC 1766 UCCGAUAG CUGAUGAG 1184 CAACAGCUU 1885 X CGAA AGCUGUUG CUAUCGGA 1767 GUCCGAUA CUGAUGAG 1185 AACAGCUUC 1886 10 X CGAA AAGCUGUU UAUCGGAC 1769 GAGUCCGA CUGAUGAG 1186 CAGCUUCUA 1887 X CGAA AGAAGCUG UCGGACUC 1771 GGGAGUCC CUGAUGAG 1187 GCUUCUAUC 1888 X CGAA AUAGAAGC GGACUCCC 15 1777 GGAGGAGG CUGAUGAG 1188 AUCGGACUC 1889 X CGAA AGUCCGAU CCUCCUCC 1781 UCUUGGAG CUGAUGAG 1189 GACUCCCUC 1890 X CGAA AGGGAGUC CUCCAAGA 1784 ACCUCUUG CUGAUGAG 1190 UCCCUCCUC 1891 20 X CGAA AGGAGGGA CAAGAGGU 1793 GAGAUUUA CUGAUGAG 1191 CAAGAGGUC 1892 X CGAA ACCUCUUG UAAAUCUC 1795 AGGAGAUU CUGAUGAG 1192 AGAGGUCUA 1893 X CGAA AGACCUCU AAUCUCCU 25 1799 AGGCAGGA CUGAUGAG 1193 GUCUAAAUC 1894 X CGAA AUUUAGAC UCCUGCCU 1801 UUAGGCAG CUGAUGAG 1194 CUAAAUCUC 1895 X CGAA AGAUUUAG CUGCCUAA 1808 CUGACUUU CUGAUGAG 1195 UCCUGCCUA 1896 30 X CGAA AGGCAGGA AAAGUCAG 1814 AGUGGUCU CUGAUGAG 1196 CUAAAAGUC 1897 X CGAA ACUUUUAG AGACCACU 1823 CAAAUUUA CUGAUGAG 1197 AGACCACUC 1898 X CGAA AGUGGUCU UAAAUUUG WO 99/50403 PCT/US99/06507 110 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1825 GUCAAAUU CUGAUGAG 1198 ACCACUCUA 1899 X CGAA AGAGUGGU AAUUUGAC 5 1829 CCAGGUCA CUGAUGAG 1199 CUCUAAAUU 1900 X CGAA AUUUAGAG UGACCUGG 1830 GCCAGGUC CUGAUGAG 1200 UCUAAAUUU 1901 X CGAA AAUUUAGA GACCUGGC 1846 CUUGGAAA CUGAUGAG 1201 CAACCAAUA 1902 10 X CGAA AUUGGUUG UUUCCAAG 1848 AGCUUGGA CUGAUGAG 1202 ACCAAUAUU 1903 X CGAA AUAUUGGU UCCAAGCU 1849 GAGCUUGG CUGAUGAG 1203 CCAAUAUUU 1904 X CGAA AAUAUUGG CCAAGCUC 15 1850 CGAGCUUG CUGAUGAG 1204 CAAUAUUUC 1905 X CGAA AAAUAUUG CAAGCUCG 1857 CAUCUUCC CUGAUGAG 1205 UCCAAGCUC 1906 X CGAA AGCUUGGA GGAAGAUG 1869 CAACAUAA CUGAUGAG 1206 AGAUGACUU 1907 20 X CGAA AGUCAUCU UUAUGUUG 1870 UCAACAUA CUGAUGAG 1207 GAUGACUUU 1908 X CGAA AAGUCAUC UAUGUUGA 1871 UUCAACAU CUGAUGAG 1208 AUGACUUUU 1909 X CGAA AAAGUCAU AUGUUGAA 25 1872 CUUCAACA CUGAUGAG 1209 UGACUUUUA 1910 X CGAA AAAAGUCA UGUUGAAG 1876 UCCACUUC CUGAUGAG 1210 UUUUAUGUU 1911 X CGAA ACAUAAAA GAAGUGGA 1893 UUUGCACA CUGAUGAG 1211 GAGAAGGUC 1912 30 X CGAA ACCUUCUC UGUGCAAA 1910 AUUCUGCU CUGAUGAG 1212 AAAGUGAUC 1913 X CGAA AUCACUUU AGCAGAAU 1919 AACUUUAA CUGAUGAG 1213 AGCAGAAUA 1914 X CGAA AUUCUGCU UUAAAGUU WO 99/50403 PCT/US99/06507 111 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1921 GGAACUUU CUGAUGAG 1214 CAGAAUAUU 1915 X CGAA AUAUUCUG AAAGUUCC 5 1922 UGGAACUU CUGAUGAG 1215 AGAAUAUUA 1916 X CGAA AAUAUUCU AAGUUCCA 1927 UUGCCUGG CUGAUGAG 1216 AUUAAAGUU 1917 X CGAA ACUUUAAU CCAGGCAA 1928 GUUGCCUG CUGAUGAG 1217 UUAAAGUUC 1918 10 X CGAA AACUUUAA CAGGCAAC 1938 CCGAAGUC CUGAUGAG 1218 AGGCAACUU 1919 X CGAA AGUUGCCU GACUUCGG 1943 UAGCACCG CUGAUGAG 1219 ACUUGACUU 1920 X CGAA AGUCAAGU CGGUGCUA 15 1944 GUAGCACC CUGAUGAG 1220 CUUGACUUC 1921 X CGAA AAGUCAAG GGUGCUAC 1951 UUGUUAAG CUGAUGAG 1221 UCGGUGCUA 1922 X CGAA AGCACCGA CUUAACAA 1954 AAGUUGUU CUGAUGAG 1222 GUGCUACUU 1923 20 X CGAA AGUAGCAC AACAACUU 1955 UAAGUUGU CUGAUGAG 1223 UGCUACUUA 1924 X CGAA AAGUAGCA ACAACUUA 1962 UGGGAUGU CUGAUGAG 1224 UAACAACUU 1925 X CGAA AGUUGUUA ACAUCCCA 25 1963 CUGGGAUG CUGAUGAG 1225 AACAACUUA 1926 X CGAA AAGUUGUU CAUCCCAG 1967 CUCCCUGG CUGAUGAG 1226 ACUUACAUC 1927 X CGAA AUGUAAGU CCAGGGAG 1980 GGACCACG CUGAUGAG 1227 GGAGCAGUA 1928 30 X CGAA ACUGCUCC CGUGGUCC 1987 CUAGCUCG CUGAUGAG 1228 UACGUGGUC 1929 X CGAA ACCACGUA CGAGCUAG 1994 GUUGACUC CUGAUGAG 1229 UCCGAGCUA 1930 X CGAA AGCUCGGA GAGUCAAC WO 99/50403 PCT/US99/06507 112 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1999 UUGGUGUU CUGAUGAG 1230 GCUAGAGUC 1931 X CGAA ACUCUAGC AACACCAA 5 2033 AGCAGUGA CUGAUGAG 1231 GUGAAGAUC 1932 X CGAA AUCUUCAC UCACUGCU 2035 CAAGCAGU CUGAUGAG 1232 GAAGAUCUC 1933 X CGAA AGAUCUUC ACUGCUUG 2042 AAGGGUCC CUGAUGAG 1233 UCACUGCUU 1934 10 X CGAA AGCAGUGA GGACCCUU 2050 AUGUCACU CUGAUGAG 1234 UGGACCCUU 1935 X CGAA AGGGUCCA AGUGACAU 2051 AAUGUCAC CUGAUGAG 1235 GGACCCUUA 1936 X CGAA AAGGGUCC GUGACAUU 15 2059 GGAGGAAG CUGAUGAG 1236 AGUGACAUU 1937 X CGAA AUGUCACU CUUCCUCC 2060 AGGAGGAA CUGAUGAG 1237 GUGACAUUC 1938 X CGAA AAUGUCAC UUCCUCCU 2062 UGAGGAGG CUGAUGAG 1238 GACAUUCUU 1939 20 X CGAA AGAAUGUC CCUCCUCA 2063 UUGAGGAG CUGAUGAG 1239 ACAUUCUUC 1940 X CGAA AAGAAUGU CUCCUCAA 2066 UGGUUGAG CUGAUGAG 1240 UUCUUCCUC 1941 X CGAA AGGAAGAA CUCAACCA 25 2069 UUCUGGUU CUGAUGAG 1241 UUCCUCCUC 1942 X CGAA AGGAGGAA AACCAGAA 2083 GAAAUCUU CUGAUGAG 1242 GAAAACAUC 1943 X CGAA AUGUUUUC AAGAUUUC 2089 AUGUUGGA CUGAUGAG 1243 AUCAAGAUU 1944 30 X CGAA AUCUUGAU UCCAACAU 2090 AAUGUUGG CUGAUGAG 1244 UCAAGAUUU 1945 X CGAA AAUCUUGA CCAACAUU 2091 UAAUGUUG CUGAUGAG 1245 CAAGAUUUC 1946 X CGAA AAAUCUUG CAACAUUA WO 99/50403 PCT/US99/06507 113 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2098 GAGUGUGU CUGAUGAG 1246 UCCAACAUU 1947 X CGAA AUGUUGGA ACACACUC 5 2099 GGAGUGUG CUGAUGAG 1247 CCAACAUUA 1948 X CGAA AAUGUUGG CACACUCC 2106 CAGCCGAG CUGAUGAG 1248 UACACACUC 1949 X CGAA AGUGUGUA CUCGGCUG 2109 UCACAGCC CUGAUGAG 1249 ACACUCCUC 1950 10 X CGAA AGGAGUGU GGCUGUGA 2119 GUCCAAGA CUGAUGAG 1250 GCUGUGAUU 1951 X CGAA AUCACAGC UCUUGGAC 2120 UGUCCAAG CUGAUGAG 1251 CUGUGAUUU 1952 X CGAA AAUCACAG CUUGGACA 15 2121 UUGUCCAA CUGAUGAG 1252 UGUGAUUUC 1953 X CGAA AAAUCACA UUGGACAA 2123 UAUUGUCC CUGAUGAG 1253 UGAUUUCUU 1954 X CGAA AGAAAUCA GGACAAUA 2131 CCAUCCAA CUGAUGAG 1254 UGGACAAUA 1955 20 X CGAA AUUGUCCA UUGGAUGG 2133 AGCCAUCC CUGAUGAG 1255 GACAAUAUU 1956 X CGAA AUAUUGUC GGAUGGCU 2142 AAAUAGAA CUGAUGAG 1256 GGAUGGCUA 1957 X CGAA AGCCAUCC UUCUAUUU 25 2144 AGAAAUAG CUGAUGAG 1257 AUGGCUAUU 1958 X CGAA AUAGCCAU CUAUUUCU 2145 AAGAAAUA CUGAUGAG 1258 UGGCUAUUC 1959 X CGAA AAUAGCCA UAUUUCUU 2147 AGAAGAAA CUGAUGAG 1259 GCUAUUCUA 1960 30 X CGAA AGAAUAGC UUUCUUCU 2149 AUAGAAGA CUGAUGAG 1260 UAUUCUAUU 1961 X CGAA AUAGAAUA UCUUCUAU 2150 AAUAGAAG CUGAUGAG 1261 AUUCUAUUU 1962 X CGAA AAUAGAAU CUUCUAUU WO 99/50403 PCT/US99/06507 114 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2151 UAAUAGAA CUGAUGAG 1262 UUCUAUUUC 1963 X CGAA AAAUAGAA UUCUAUUA 5 2153 AGUAAUAG CUGAUGAG 1263 CUAUUUCUU 1964 X CGAA AGAAAUAG CUAUUACU 2154 UAGUAAUA CUGAUGAG 1264 UAUUUCUUC 1965 X CGAA AAGAAAUA UAUUACUA 2156 GAUAGUAA CUGAUGAG 1265 UUUCUUCUA 1966 10 X CGAA AGAAGAAA UUACUAUC 2158 CGGAUAGU CUGAUGAG 1266 UCUUCUAUU 1967 X CGAA AUAGAAGA ACUAUCCG 2159 ACGGAUAG CUGAUGAG 1267 CUUCUAUUA 1968 X CGAA AAUAGAAG CUAUCCGU 15 2162 GUAACGGA CUGAUGAG 1268 CUAUUACUA 1969 X CGAA AGUAAUAG UCCGUUAC 2164 UUGUAACG CUGAUGAG 1269 AUUACUAUC 1970 X CGAA AUAGUAAU CGUUACAA 2168 AACCUUGU CUGAUGAG 1270 CUAUCCGUU 1971 20 X CGAA ACGGAUAG ACAAGGUU 2169 GAACCUUG CUGAUGAG 1271 UAUCCGUUA 1972 X CGAA AACGGAUA CAAGGUUC 2176 UUGCCUUG CUGAUGAG 1272 UACAAGGUU 1973 X CGAA ACCUUGUA CAAGGCAA 25 2177 CUUGCCUU CUGAUGAG 1273 ACAAGGUUC 1974 X CGAA AACCUUGU AAGGCAAG 2203 UUCACAUC CUGAUGAG 1274 CAGCACGUU 1975 X CGAA ACGUGCUG GAUGUGAA 2215 GCAUUCUU CUGAUGAG 1275 GUGAAGAUA 1976 30 X CGAA AUCUUCAC AAGAAUGC 2230 UACUGAAU CUGAUGAG 1276 GCCACCAUC 1977 X CGAA AUGGUGGC AUUCAGUA 2233 UGAUACUG CUGAUGAG 1277 ACCAUCAUU 1978 X CGAA AUGAUGGU CAGUAUCA WO 99/50403 PCT/US99/06507 115 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2234 CUGAUACU CUGAUGAG 1278 CCAUCAUUC 1979 X CGAA AAUGAUGG AGUAUCAG 5 2238 UGAGCUGA CUGAUGAG 1279 CAUUCAGUA 1980 X CGAA ACUGAAUG UCAGCUCA 2240 CUUGAGCU CUGAUGAG 1280 UUCAGUAUC 1981 X CGAA AUACUGAA AGCUCAAG 2245 AGGCCCUU CUGAUGAG 1281 UAUCAGCUC 1982 10 X CGAA AGCUGAUA AAGGGCCU 2254 UCAGGCUC CUGAUGAG 1282 AAGGGCCUA 1983 X CGAA AGGCCCUU GAGCCUGA 2271 CCACCUGG CUGAUGAG 1283 AACAGCAUA 1984 X CGAA AUGCUGUU CCAGGUGG 15 2284 UCUGCAAA CUGAUGAG 1284 GUGGACAUU 1985 X CGAA AUGUCCAC UUUGCAGA 2285 CUCUGCAA CUGAUGAG 1285 UGGACAUUU 1986 X CGAA AAUGUCCA UUGCAGAG 2286 UCUCUGCA CUGAUGAG 1286 GGACAUUUU 1987 20 X CGAA AAAUGUCC UGCAGAGA 2287 UUCUCUGC CUGAUGAG 1287 GACAUUUUU 1988 X CGAA AAAAUGUC GCAGAGAA 2302 CUUGACCC CUGAUGAG 1288 AACAACAUA 1989 X CGAA AUGUUGUU GGGUCAAG 25 2307 GGUUGCUU CUGAUGAG 1289 CAUAGGGUC 1990 X CGAA ACCCUAUG AAGCAACC 2322 CAUGAGAA CUGAUGAG 1290 CCCAGCCUU 1991 X CGAA AGGCUGGG UUCUCAUG 2323 UCAUGAGA CUGAUGAG 1291 CCAGCCUUU 1992 30 X CGAA AAGGCUGG UCUCAUGA 2324 UUCAUGAG CUGAUGAG 1292 CAGCCUUUU 1993 X CGAA AAAGGCUG CUCAUGAA 2325 GUUCAUGA CUGAUGAG 1293 AGCCUUUUC 1994 X CGAA AAAAGGCU UCAUGAAC WO 99/50403 PCT/US99/06507 116 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2327 CAGUUCAU CUGAUGAG 1294 CCUUUUCUC 1995 X CGAA AGAAAAGG AUGAACUG 5 2344 GAUUCUGG CUGAUGAG 1295 GUGACCCUC 1996 X CGAA AGGGUCAC CCAGAAUC 2352 GUGCUUGA CUGAUGAG 1296 CCCAGAAUC 1997 X CGAA AUUCUGGG UCAAGCAC 2354 UGGUGCUU CUGAUGAG 1297 CAGAAUCUC 1998 10 X CGAA AGAUUCUG AAGCACCA 2371 CCCCCUCC CUGAUGAG 1298 GCGGACCUC 1999 X CGAA AGGUCCGC GGAGGGGG 2392 AUGGCUAU CUGAUGAG 1299 AUGCUGCUU 2000 X CGAA AGCAGCAU AUAGCCAU 15 2393 GAUGGCUA CUGAUGAG 1300 UGCUGCUUA 2001 X CGAA AAGCAGCA UAGCCAUC 2395 AGGAUGGC CUGAUGAG 1301 CUGCUUAUA 2002 X CGAA AUAAGCAG GCCAUCCU 2401 GAGCCAAG CUGAUGAG 1302 AUAGCCAUC 2003 20 X CGAA AUGGCUAU CUUGGCUC 2404 GCAGAGCC CUGAUGAG 1303 GCCAUCCUU 2004 X CGAA AGGAUGGC GGCUCUGC 2409 UUCCAGCA CUGAUGAG 1304 CCUUGGCUC 2005 X CGAA AGCCAAGG UGCUGGAA 25 2439 GAAAGGCC CUGAUGAG 1305 UGUGCUGUU 2006 X CGAA ACAGCACA GGCCUUUC 2445 UGAUCAGA CUGAUGAG 1306 GUUGGCCUU 2007 X CGAA AGGCCAAC UCUGAUCA 2446 AUGAUCAG CUGAUGAG 1307 UUGGCCUUU 2008 30 X CGAA AAGGCCAA CUGAUCAU 2447 UAUGAUCA CUGAUGAG 1308 UGGCCUUUC 2009 X CGAA AAAGGCCA UGAUCAUA 2452 UGCAAUAU CUGAUGAG 1309 UUUCUGAUC 2010 X CGAA AUCAGAAA AUAUUGCA WO 99/50403 PCT/US99/06507 117 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2455 AAUUGCAA CUGAUGAG 1310 CUGAUCAUA 2011 X CGAA AUGAUCAG UUGCAAUU 5 2457 UCAAUUGC CUGAUGAG 1311 GAUCAUAUU 2012 X CGAA AUAUGAUC GCAAUUGA 2463 CCCUCUUC CUGAUGAG 1312 AUUGCAAUU 2013 X CGAA AUUGCAAU GAAGAGGG 2502 CGUUUUGG CUGAUGAG 1313 CCAAGCCUU 2014 10 X CGAA AGGCUUGG CCAAAACG 2503 ACGUUUUG CUGAUGAG 1314 CAAGCCUUC 2015 X CGAA AAGGCUUG CAAAACGU 2535 CUGAGUUG CUGAUGAG 1315 UGUGCAGUU 2016 X CGAA ACUGCACA CAACUCAG 15 2536 CCUGAGUU CUGAUGAG 1316 GUGCAGUUC 2017 X CGAA AACUGCAC AACUCAGG 2541 GAGUCCCU CUGAUGAG 1317 GUUCAACUC 2018 X CGAA AGUUGAAC AGGGACUC 2549 UAGGGCCA CUGAUGAG 1318 CAGGGACUC 2019 20 X CGAA AGUCCCUG UGGCCCUA 2557 UUCCUGUU CUGAUGAG 1319 CUGGCCCUA 2020 X CGAA AGGGCCAG AACAGGAA 2569 UUGUUUUU CUGAUGAG 1320 AGGAAGGUC 2021 X CGAA ACCUUCCU AAAAACAA 25 2585 AAUUGUAG CUGAUGAG 1321 ACCCAGAUC 2022 X CGAA AUCUGGGU CUACAAUU 2588 AUAAAUUG CUGAUGAG 1322 CAGAUCCUA 2023 X CGAA AGGAUCUG CAAUUUAU 2593 ACUGGAUA CUGAUGAG 1323 CCUACAAUU 2024 30 X CGAA AUUGUAGG UAUCCAGU 2594 CACUGGAU CUGAUGAG 1324 CUACAAUUU 2025 X CGAA AAUUGUAG AUCCAGUG 2595 GCACUGGA CUGAUGAG 1325 UACAAUUUA 2026 X CGAA AAAUUGUA UCCAGUGC WO 99/50403 PCT/US99/06507 118 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2597 AAGCACUG CUGAUGAG 1326 CAAUUUAUC 2027 X CGAA AUAAAUUG CAGUGCUU 5 2605 UUCCAGUC CUGAUGAG 1327 CCAGUGCUU 2028 X CGAA AGCACUGG GACUGGAA 2620 UGAAAUUU CUGAUGAG 1328 AAUGACAUC 2029 X CGAA AUGUCAUU AAAUUUCA 2625 CAUCUUGA CUGAUGAG 1329 CAUCAAAUU 2030 10 X CGAA AUUUGAUG UCAAGAUG 2626 ACAUCUUG CUGAUGAG 1330 AUCAAAUUU 2031 X CGAA AAUUUGAU CAAGAUGU 2627 CACAUCUU CUGAUGAG 1331 UCAAAUUUC 2032 X CGAA AAAUUUGA AAGAUGUG 15 2638 CCCUCCCC CUGAUGAG 1332 GAUGUGAUU 2033 X CGAA AUCACAUC GGGGAGGG 2651 UUGGCCAA CUGAUGAG 1333 AGGGCAAUU 2034 X CGAA AUUGCCCU UUGGCCAA 2652 CUUGGCCA CUGAUGAG 1334 GGGCAAUUU 2035 20 X CGAA AAUUGCCC UGGCCAAG 2653 ACUUGGCC CUGAUGAG 1335 GGCAAUUUU 2036 X CGAA AAAUUGCC GGCCAAGU 2662 GCCUUAAG CUGAUGAG 1336 GGCCAAGUU 2037 X CGAA ACUUGGCC CUUAAGGC 25 2663 CGCCUUAA CUGAUGAG 1337 GCCAAGUUC 2038 X CGAA AACUUGGC UUAAGGCG 2665 CGCGCCUU CUGAUGAG 1338 CAAGUUCUU 2039 X CGAA AGAACUUG AAGGCGCG 2666 GCGCGCCU CUGAUGAG 1339 AAGUUCUUA 2040 30 X CGAA AAGAACUU AGGCGCGC 2677 UCCUUCUU CUGAUGAG 1340 GCGCGCAUC 2041 X CGAA AUGCGCGC AAGAAGGA 2691 CCAUCCGU CUGAUGAG 1341 GGAUGGGUU 2042 X CGAA ACCCAUCC ACGGAUGG WO 99/50403 PCTIUS99/06507 119 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2692 UCCAUCCG CUGAUGAG 1342 GAUGGGUUA 2043 X CGAA AACCCAUC CGGAUGGA 5 2710 AUUCUUUU CUGAUGAG 1343 GCUGCCAUC 2044 X CGAA AUGGCAGC AAAAGAAU 2727 UGGAGGCA CUGAUGAG 1344 GAAAGAAUA 2045 X CGAA AUUCUUUC UGCCUCCA 2733 CAUCUUUG CUGAUGAG 1345 AUAUGCCUC 2046 10 X CGAA AGGCAUAU CAAAGAUG 2744 GUCCCUGU CUGAUGAG 1346 AAGAUGAUC 2047 X CGAA AUCAUCUU ACAGGGAC 2754 CUCCUGCA CUGAUGAG 1347 CAGGGACUU 2048 X CGAA AGUCCCUG UGCAGGAG 15 2755 UCUCCUGC CUGAUGAG 1348 AGGGACUUU 2049 X CGAA AAGUCCCU GCAGGAGA 2773 UUACAAAG CUGAUGAG 1349 CUGGAAGUU 2050 X CGAA ACUUCCAG CUUUGUAA 2774 UUUACAAA CUGAUGAG 1350 UGGAAGUUC 2051 20 X CGAA AACUUCCA UUUGUAAA 2776 AGUUUACA CUGAUGAG 1351 GAAGUUCUU 2052 X CGAA AGAACUUC UGUAAACU 2777 AAGUUUAC CUGAUGAG 1352 AAGUUCUUU 2053 X CGAA AAGAACUU GUAAACUU 25 2780 UCCAAGUU CUGAUGAG 1353 UUCUUUGUA 2054 X CGAA ACAAAGAA AACUUGGA 2785 UGGUGUCC CUGAUGAG 1354 UGUAAACUU 2055 X CGAA AGUUUACA GGACACCA 2795 GAUGUUUG CUGAUGAG 1355 GACACCAUC 2056 30 X CGAA AUGGUGUC CAAACAUC 2803 AGAUUGAU CUGAUGAG 1356 CCAAACAUC 2057 X CGAA AUGUUUGG AUCAAUCU 2806 AAGAGAUU CUGAUGAG 1357 AACAUCAUC 2058 X CGAA AUGAUGUU AAUCUCUU WO 99/50403 PCT/US99/06507 120 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2810 UCCUAAGA CUGAUGAG 1358 UCAUCAAUC 2059 X CGAA AUUGAUGA UCUUAGGA 5 2812 GCUCCUAA CUGAUGAG 1359 AUCAAUCUC 2060 X CGAA AGAUUGAU UUAGGAGC 2814 AUGCUCCU CUGAUGAG 1360 CAAUCUCUU 2061 X CGAA AGAGAUUG AGGAGCAU 2815 CAUGCUCC CUGAUGAG 1361 AAUCUCUUA 2062 10 X CGAA AAGAGAUU GGAGCAUG 2831 GUAGCCUC CUGAUGAG 1362 GUGAACAUC 2063 X CGAA AUGUUCAC GAGGCUAC 2838 GGUACAAG CUGAUGAG 1363 UCGAGGCUA 2064 X CGAA AGCCUCGA CUUGUACC 15 2841 CCAGGUAC CUGAUGAG 1364 AGGCUACUU 2065 X CGAA AGUAGCCU GUACCUGG 2844 UGGCCAGG CUGAUGAG 1365 CUACUUGUA 2066 X CGAA ACAAGUAG CCUGGCCA 2854 GCGUACUC CUGAUGAG 1366 CUGGCCAUU 2067 20 X CGAA AUGGCCAG GAGUACGC 2859 GGGGCGCG CUGAUGAG 1367 CAUUGAGUA 2068 X CGAA ACUCAAUG CGCGCCCC 2878 AAGUCCAG CUGAUGAG 1368 GGAAACCUU 2069 X CGAA AGGUUUCC CUGGACUU 25 2879 GAAGUCCA CUGAUGAG 1369 GAAACCUUC 2070 X CGAA AAGGUUUC UGGACUUC 2886 UGCGAAGG CUGAUGAG 1370 UCUGGACUU 2071 X CGAA AGUCCAGA CCUUCGCA 2887 UUGCGAAG CUGAUGAG 1371 CUGGACUUC 2072 30 X CGAA AAGUCCAG CUUCGCAA 2890 CUCUUGCG CUGAUGAG 1372 GACUUCCUU 2073 X CGAA AGGAAGUC CGCAAGAG 2891 GCUCUUGC CUGAUGAG 1373 ACUUCCUUC 2074 X CGAA AAGGAAGU GCAAGAGC WO 99/50403 PCT/US99/06507 121 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2925 CAAUGGCA CUGAUGAG 1374 CCCAGCAUU 2075 X CGAA AUGCUGGG UGCCAUUG 5 2926 GCAAUGGC CUGAUGAG 1375 CCAGCAUUU 2076 X CGAA AAUGCUGG GCCAUUGC 2932 CUAUUGGC CUGAUGAG 1376 UUUGCCAUU 2077 X CGAA AUGGCAAA GCCAAUAG 2939 CGCGGUGC CUGAUGAG 1377 UUGCCAAUA 2078 10 X CGAA AUUGGCAA GCACCGCG 2949 ACAGUGUG CUGAUGAG 1378 CACCGCGUC 2079 X CGAA ACGCGGUG CACACUGU 2958 GCUGGGAG CUGAUGAG 1379 CACACUGUC 2080 X CGAA ACAGUGUG CUCCCAGC 15 2961 GCUGCUGG CUGAUGAG 1380 ACUGUCCUC 2081 X CGAA AGGACAGU CCAGCAGC 2971 AAGUGAAG CUGAUGAG 1381 CAGCAGCUC 2082 X CGAA AGCUGCUG CUUCACUU 2974 GCGAAGUG CUGAUGAG 1382 CAGCUCCUU 2083 20 X CGAA AGGAGCUG CACUUCGC 2975 AGCGAAGU CUGAUGAG 1383 AGCUCCUUC 2084 X CGAA AAGGAGCU ACUUCGCU 2979 CGGCAGCG CUGAUGAG 1384 CCUUCACUU 2085 X CGAA AGUGAAGG CGCUGCCG 25 2980 UCGGCAGC CUGAUGAG 1385 CUUCACUUC 2086 X CGAA AAGUGAAG GCUGCCGA 3009 GGCUCAAG CUGAUGAG 1386 CAUGGACUA 2087 X CGAA AGUCCAUG CUUGAGCC 3012 UUUGGCUC CUGAUGAG 1387 GGACUACUU 2088 30 X CGAA AGUAGUCC GAGCCAAA 3027 UGUGGAUA CUGAUGAG 1388 AAAACAGUU 2089 X CGAA ACUGUUUU UAUCCACA 3028 CUGUGGAU CUGAUGAG 1389 AAACAGUUU 2090 X CGAA AACUGUUU AUCCACAG WO 99/50403 PCT/US99/06507 122 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3029 CCUGUGGA CUGAUGAG 1390 AACAGUUUA 2091 X CGAA AAACUGUU UCCACAGG 5 3031 UCCCUGUG CUGAUGAG 1391 CAGUUUAUC 2092 X CGAA AUAAACUG CACAGGGA 3041 GGCAGCCA CUGAUGAG 1392 ACAGGGAUC 2093 X CGAA AUCCCUGU UGGCUGCC 3058 CCAACUAA CUGAUGAG 1393 AGAAACAUU 2094 10 X CGAA AUGUUUCU UUAGUUGG 3059 ACCAACUA CUGAUGAG 1394 GAAACAUUU 2095 X CGAA AAUGUUUC UAGUUGGU 3060 CACCAACU CUGAUGAG 1395 AAACAUUUU 2096 X CGAA AAAUGUUU AGUUGGUG 15 3061 UCACCAAC CUGAUGAG 1396 AACAUUUUA 2097 X CGAA AAAAUGUU GUUGGUGA 3064 UUUUCACC CUGAUGAG 1397 AUUUUAGUU 2098 X CGAA ACUAAAAU GGUGAAAA 3075 UUGCCACA CUGAUGAG 1398 UGAAAACUA 2099 20 X CGAA AGUUUUCA UGUGGCAA 3088 AAAUCUGC CUGAUGAG 1399 GCAAAAAUA 2100 X CGAA AUUUUUGC GCAGAUUU 3095 CAAUCCAA CUGAUGAG 1400 UAGCAGAUU 2101 X CGAA AUCUGCUA UUGGAUUG 25 3096 ACAAUCCA CUGAUGAG 1401 AGCAGAUUU 2102 X CGAA AAUCUGCU UGGAUUGU 3097 GACAAUCC CUGAUGAG 1402 GCAGAUUUU 2103 X CGAA AAAUCUGC GGAUUGUC 3102 CUCGGGAC CUGAUGAG 1403 UUUUGGAUU 2104 30 X CGAA AUCCAAAA GUCCCGAG 3105 GACCUCGG CUGAUGAG 1404 UGGAUUGUC 2105 X CGAA ACAAUCCA CCGAGGUC 3113 CACCUCUU CUGAUGAG 1405 CCCGAGGUC 2106 X CGAA ACCUCGGG AAGAGGUG WO 99/50403 PCTIUS99/06507 123 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3123 UUUUCACG CUGAUGAG 1406 AGAGGUGUA 2107 X CGAA ACACCUCU CGUGAAAA 5 3148 CGCACUGG CUGAUGAG 1407 GGAAGGCUC 2108 X CGAA AGCCUUCC CCAGUGCG 3169 AGUGACUC CUGAUGAG 1408 AUGGCCAUC 2109 X CGAA AUGGCCAU GAGUCACU 3174 AAUUCAGU CUGAUGAG 1409 CAUCGAGUC 2110 10 X CGAA ACUCGAUG ACUGAAUU 3182 CACACUGU CUGAUGAG 1410 CACUGAAUU 2111 X CGAA AUUCAGUG ACAGUGUG 3183 ACACACUG CUGAUGAG 1411 ACUGAAUUA 2112 X CGAA AAUUCAGU CAGUGUGU 15 3192 UGGUUGUG CUGAUGAG 1412 CAGUGUGUA 2113 X CGAA ACACACUG CACAACCA 3211 UAGGACCA CUGAUGAG 1413 AGUGAUGUA 2114 X CGAA ACAUCACU UGGUCCUA 3216 CACCAUAG CUGAUGAG 1414 UGUAUGGUC 2115 20 X CGAA ACCAUACA CUAUGGUG 3219 ACACACCA CUGAUGAG 1415 AUGGUCCUA 2116 X CGAA AGGACCAU UGGUGUGU 3228 CCCAUAGU CUGAUGAG 1416 UGGUGUGUU 2117 X CGAA ACACACCA ACUAUGGG 25 3229 UCCCAUAG CUGAUGAG 1417 GGUGUGUUA 2118 X CGAA AACACACC CUAUGGGA 3232 AUCUCCCA CUGAUGAG 1418 GUGUUACUA 2119 X CGAA AGUAACAC UGGGAGAU 3241 AAGCUAAC CUGAUGAG 1419 UGGGAGAUU 2120 30 X CGAA AUCUCCCA GUUAGCUU 3244 CCUAAGCU CUGAUGAG 1420 GAGAUUGUU 2121 X CGAA ACAAUCUC AGCUUAGG 3245 UCCUAAGC CUGAUGAG 1421 AGAUUGUUA 2122 X CGAA AACAAUCU GCUUAGGA WO 99/50403 PCTIUS99/06507 124 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3249 UGCCUCCU CUGAUGAG 1422 UGUUAGCUU 2123 X CGAA AGCUAACA AGGAGGCA 5 3250 GUGCCUCC CUGAUGAG 1423 GUUAGCUUA 2124 X CGAA AAGCUAAC GGAGGCAC 3264 UCCCGCAG CUGAUGAG 1424 CACACCCUA 2125 X CGAA AGGGUGUG CUGCGGGA 3278 UUCUGCAC CUGAUGAG 1425 GGAUGACUU 2126 10 X CGAA AGUCAUCC GUGCAGAA 3289 UUCUCGUA CUGAUGAG 1426 GCAGAACUC 2127 X CGAA AGUUCUGC UACGAGAA 3291 GCUUCUCG CUGAUGAG 1427 AGAACUCUA 2128 X CGAA AGAGUUCU CGAGAAGC 15 3312 CCAGUCUG CUGAUGAG 1428 CCAGGGCUA 2129 X CGAA AGCCCUGG CAGACUGG 3351 UUAGAUCA CUGAUGAG 1429 UGAGGUGUA 2130 X CGAA ACACCUCA UGAUCUAA 3356 UCUCAUUA CUGAUGAG 1430 UGUAUGAUC 2131 20 X CGAA AUCAUACA UAAUGAGA 3358 UGUCUCAU CUGAUGAG 1431 UAUGAUCUA 2132 X CGAA AGAUCAUA AUGAGACA 3386 CCUCUCAU CUGAUGAG 1432 AGAAGCCUU 2133 X CGAA AGGCUUCU AUGAGAGG 25 3387 GCCUCUCA CUGAUGAG 1433 GAAGCCUUA 2134 X CGAA AAGGCUUC UGAGAGGC 3399 GGGCAAAU CUGAUGAG 1434 GAGGCCAUC 2135 X CGAA AUGGCCUC AUUUGCCC 3402 UCUGGGCA CUGAUGAG 1435 GCCAUCAUU 2136 30 X CGAA AUGAUGGC UGCCCAGA 3403 AUCUGGGC CUGAUGAG 1436 CCAUCAUUU 2137 X CGAA AAUGAUGG GCCCAGAU 3412 GACACCAA CUGAUGAG 1437 GCCCAGAUA 2138 X CGAA AUCUGGGC UUGGUGUC WO 99/50403 PCT/US99/06507 125 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3414 AGGACACC CUGAUGAG 1438 CCAGAUAUU 2139 X CGAA AUAUCUGG GGUGUCCU 5 3420 UGUUUAAG CUGAUGAG 1439 AUUGGUGUC 2140 X CGAA ACACCAAU CUUAAACA 3423 UUCUGUUU CUGAUGAG 1440 GGUGUCCUU 2141 X CGAA AGGACACC AAACAGAA 3424 AUUCUGUU CUGAUGAG 1441 GUGUCCUUA 2142 10 X CGAA AAGGACAC AACAGAAU 3435 GCUCCUCU CUGAUGAG 1442 CAGAAUGUU 2143 X CGAA ACAUUCUG AGAGGAGC 3436 CGCUCCUC CUGAUGAG 1443 AGAAUGUUA 2144 X CGAA AACAUUCU GAGGAGCG 15 3453 UAUUCACG CUGAUGAG 1444 AAAGACCUA 2145 X CGAA AGGUCUUU CGUGAAUA 3461 AAGCGUGG CUGAUGAG 1445 ACGUGAAUA 2146 X CGAA AUUCACGU CCACGCUU 3469 UUCUCAUA CUGAUGAG 1446 ACCACGCUU 2147 20 X CGAA AGCGUGGU UAUGAGAA 3470 CUUCUCAU CUGAUGAG 1447 CCACGCUUU 2148 X CGAA AAGCGUGG AUGAGAAG 3471 ACUUCUCA CUGAUGAG 1448 CACGCUUUA 2149 X CGAA AAAGCGUG UGAGAAGU 25 3480 CAUAAGUA CUGAUGAG 1449 UGAGAAGUU 2150 X CGAA ACUUCUCA UACUUAUG 3481 GCAUAAGU CUGAUGAG 1450 GAGAAGUUU 2151 X CGAA AACUUCUC ACUUAUGC 3482 UGCAUAAG CUGAUGAG 1451 AGAAGUUUA 2152 30 X CGAA AAACUUCU CUUAUGCA 3485 UCCUGCAU CUGAUGAG 1452 AGUUUACUU 2153 X CGAA AGUAAACU AUGCAGGA 3486 UUCCUGCA CUGAUGAG 1453 GUUUACUUA 2154 X CGAA AAGUAAAC UGCAGGAA WO 99/50403 PCT/US99/06507 126 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3496 GAACAGUC CUGAUGAG 1454 GCAGGAAUU 2155 X CGAA AUUCCUGC GACUGUUC 5 3503 UUCAGCAG CUGAUGAG 1455 UUGACUGUU 2156 X CGAA ACAGUCAA CUGCUGAA 3504 CUUCAGCA CUGAUGAG 1456 UGACUGUUC 2157 X CGAA AACAGUCA UGCUGAAG 3522 UUCUGUCC CUGAUGAG 1457 AGCGGCCUA 2158 10 X CGAA AGGCCGCU GGACAGAA 3534 GGUAUACA CUGAUGAG 1458 CAGAACAUC 2159 X CGAA AUGUUCUG UGUAUACC 3538 AGAGGGUA CUGAUGAG 1459 ACAUCUGUA 2160 X CGAA ACAGAUGU UACCCUCU 15 3540 ACAGAGGG CUGAUGAG 1460 AUCUGUAUA 2161 X CGAA AUACAGAU CCCUCUGU 3545 GGGAAACA CUGAUGAG 1461 UAUACCCUC 2162 X CGAA AGGGUAUA UGUUUCCC 3549 GAAAGGGA CUGAUGAG 1462 CCCUCUGUU 2163 20 X CGAA ACAGAGGG UCCCUUUC 3550 UGAAAGGG CUGAUGAG 1463 CCUCUGUUU 2164 X CGAA AACAGAGG CCCUUUCA 3551 GUGAAAGG CUGAUGAG 1464 CUCUGUUUC 2165 X CGAA AAACAGAG CCUUUCAC 25 3555 GCCAGUGA CUGAUGAG 1465 GUUUCCCUU 2166 X CGAA AGGGAAAC UCACUGGC 3556 UGCCAGUG CUGAUGAG 1466 UUUCCCUUU 2167 X CGAA AAGGGAAA CACUGGCA 3557 AUGCCAGU CUGAUGAG 1467 UUCCCUUUC 2168 30 X CGAA AAAGGGAA ACUGGCAU 3576 CAGUUGUC CUGAUGAG 1468 GAGACCCUU 2169 X CGAA AGGGUCUC GACAACUG 3601 CUUUGGCA CUGAUGAG 1469 ACAUGCCUC 2170 X CGAA AGGCAUGU UGCCAAAG WO 99/50403 PCT/US99/06507 127 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3618 CACUUAUA CUGAUGAG 1470 GAUGUGAUA 2171 X CGAA AUCACAUC UAUAAGUG 5 3620 UACACUUA CUGAUGAG 1471 UGUGAUAUA 2172 X CGAA AUAUCACA UAAGUGUA 3622 UGUACACU CUGAUGAG 1472 UGAUAUAUA 2173 X CGAA AUAUAUCA AGUGUACA 3628 CACAUAUG CUGAUGAG 1473 AUAAGUGUA 2174 10 X CGAA ACACUUAU CAUAUGUG 3632 CCAGCACA CUGAUGAG 1474 GUGUACAUA 2175 X CGAA AUGUACAC UGUGCUGG 3644 CUUGUUAG CUGAUGAG 1475 GCUGGAAUU 2176 X CGAA AUUCCAGC CUAACAAG 15 3645 ACUUGUUA CUGAUGAG 1476 CUGGAAUUC 2177 X CGAA AAUUCCAG UAACAAGU 3647 UGACUUGU CUGAUGAG 1477 GGAAUUCUA 2178 X CGAA AGAAUUCC ACAAGUCA 3654 UAACCUAU CUGAUGAG 1478 UAACAAGUC 2179 20 X CGAA ACUUGUUA AUAGGUUA 3657 UAUUAACC CUGAUGAG 1479 CAAGUCAUA 2180 X CGAA AUGACUUG GGUUAAUA 3661 UAAAUAUU CUGAUGAG 1480 UCAUAGGUU 2181 X CGAA ACCUAUGA AAUAUUUA 25 3662 UUAAAUAU CUGAUGAG 1481 CAUAGGUUA 2182 X CGAA AACCUAUG AUAUUUAA 3665 GUCUUAAA CUGAUGAG 1482 AGGUUAAUA 2183 X CGAA AUUAACCU UUUAAGAC 3667 GUGUCUUA CUGAUGAG 1483 GUUAAUAUU 2184 30 X CGAA AUAUUAAC UAAGACAC 3668 AGUGUCUU CUGAUGAG 1484 UUAAUAUUU 2185 X CGAA AAUAUUAA AAGACACU 3669 CAGUGUCU CUGAUGAG 1485 UAAUAUUUA 2186 X CGAA AAAUAUUA AGACACUG WO 99/50403 PCT/US99/06507 128 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3684 AUCACUUA CUGAUGAG 1486 UGAAAAAUC 2187 X CGAA AUUUUUCA UAAGUGAU 5 3686 AUAUCACU CUGAUGAG 1487 AAAAAUCUA 2188 X CGAA AGAUUUUU AGUGAUAU 3693 CUGAUUUA CUGAUGAG 1488 UAAGUGAUA 2189 X CGAA AUCACUUA UAAAUCAG 3695 AUCUGAUU CUGAUGAG 1489 AGUGAUAUA 2190 10 X CGAA AUAUCACU AAUCAGAU 3699 AAGAAUCU CUGAUGAG 1490 AUAUAAAUC 2191 X CGAA AUUUAUAU AGAUUCUU 3704 GAGAGAAG CUGAUGAG 1491 AAUCAGAUU 2192 X CGAA AUCUGAUU CUUCUCUC 15 3705 AGAGAGAA CUGAUGAG 1492 AUCAGAUUC 2193 X CGAA AAUCUGAU UUCUCUCU 3707 UGAGAGAG CUGAUGAG 1493 CAGAUUCUU 2194 X CGAA AGAAUCUG CUCUCUCA 3708 AUGAGAGA CUGAUGAG 1494 AGAUUCUUC 2195 20 X CGAA AAGAAUCU UCUCUCAU 3710 AAAUGAGA CUGAUGAG 1495 AUUCUUCUC 2196 X CGAA AGAAGAAU UCUCAUUU 3712 UAAAAUGA CUGAUGAG 1496 UCUUCUCUC 2197 X CGAA AGAGAAGA UCAUUUUA 25 3714 GAUAAAAU CUGAUGAG 1497 UUCUCUCUC 2198 X CGAA AGAGAGAA AUUUUAUC 3717 AGGGAUAA CUGAUGAG 1498 UCUCUCAUU 2199 X CGAA AUGAGAGA UUAUCCCU 3718 GAGGGAUA CUGAUGAG 1499 CUCUCAUUU 2200 30 X CGAA AAUGAGAG UAUCCCUC 3719 UGAGGGAU CUGAUGAG 1500 UCUCAUUUU 2201 X CGAA AAAUGAGA AUCCCUCA 3720 GUGAGGGA CUGAUGAG 1501 CUCAUUUUA 2202 X CGAA AAAAUGAG UCCCUCAC WO 99/50403 PCT/US99/06507 129 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3722 AGGUGAGG CUGAUGAG 1502 CAUUUUAUC 2203 X CGAA AUAAAAUG CCUCACCU 5 3726 CUACAGGU CUGAUGAG 1503 UUAUCCCUC 2204 X CGAA AGGGAUAA ACCUGUAG 3733 UGGCAUGC CUGAUGAG 1504 UCACCUGUA 2205 X CGAA ACAGGUGA GCAUGCCA 3744 UGAAACGG CUGAUGAG 1505 AUGCCAGUC 2206 10 X CGAA ACUGGCAU CCGUUUCA 3749 CUAAAUGA CUGAUGAG 1506 AGUCCCGUU 2207 X CGAA ACGGGACU UCAUUUAG 3750 ACUAAAUG CUGAUGAG 1507 GUCCCGUUU 2208 X CGAA AACGGGAC CAUUUAGU 15 3751 GACUAAAU CUGAUGAG 1508 UCCCGUUUC 2209 X CGAA AAACGGGA AUUUAGUC 3754 CAUGACUA CUGAUGAG 1509 CGUUUCAUU 2210 X CGAA AUGAAACG UAGUCAUG 3755 ACAUGACU CUGAUGAG 1510 GUUUCAUUU 2211 20 X CGAA AAUGAAAC AGUCAUGU 3756 CACAUGAC CUGAUGAG 1511 UUUCAUUUA 2212 X CGAA AAAUGAAA GUCAUGUG 3759 GGUCACAU CUGAUGAG 1512 CAUUUAGUC 2213 X CGAA ACUAAAUG AUGUGACC 25 3771 ACAAGACA CUGAUGAG 1513 UGACCACUC 2214 X CGAA AGUGGUCA UGUCUUGU 3775 AAACACAA CUGAUGAG 1514 CACUCUGUC 2215 X CGAA ACAGAGUG UUGUGUUU 3777 GGAAACAC CUGAUGAG 1515 CUCUGUCUU 2216 30 X CGAA AGACAGAG GUGUUUCC 3782 GCUGUGGA CUGAUGAG 1516 UCUUGUGUU 2217 X CGAA ACACAAGA UCCACAGC 3783 GGCUGUGG CUGAUGAG 1517 CUUGUGUUU 2218 X CGAA AACACAAG CCACAGCC WO 99/50403 PCT/US99/06507 130 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3784 AGGCUGUG CUGAUGAG 1518 UUGUGUUUC 2219 X CGAA AAACACAA CACAGCCU 5 3799 CUGGACUG CUGAUGAG 1519 CUGCAAGUU 2220 X CGAA ACUUGCAG CAGUCCAG 3800 CCUGGACU CUGAUGAG 1520 UGCAAGUUC 2221 X CGAA AACUUGCA AGUCCAGG 3804 GCAUCCUG CUGAUGAG 1521 AGUUCAGUC 2222 10 X CGAA ACUGAACU CAGGAUGC 3814 UUAGAUGU CUGAUGAG 1522 AGGAUGCUA 2223 X CGAA AGCAUCCU ACAUCUAA 3819 UAUUUUUA CUGAUGAG 1523 GCUAACAUC 2224 X CGAA AUGUUAGC UAAAAAUA 15 3821 UCUAUUUU CUGAUGAG 1524 UAACAUCUA 2225 X CGAA AGAUGUUA AAAAUAGA 3827 UUUAAGUC CUGAUGAG 1525 CUAAAAAUA 2226 X CGAA AUUUUUAG GACUUAAA 3832 UGAGAUUU CUGAUGAG 1526 AAUAGACUU 2227 20 X CGAA AGUCUAUU AAAUCUCA 3833 AUGAGAUU CUGAUGAG 1527 AUAGACUUA 2228 X CGAA AAGUCUAU AAUCUCAU 3837 AGCAAUGA CUGAUGAG 1528 ACUUAAAUC 2229 X CGAA AUUUAAGU UCAUUGCU 25 3839 UAAGCAAU CUGAUGAG 1529 UUAAAUCUC 2230 X CGAA AGAUUUAA AUUGCUUA 3842 UUGUAAGC CUGAUGAG 1530 AAUCUCAUU 2231 X CGAA AUGAGAUU GCUUACAA 3846 AGGCUUGU CUGAUGAG 1531 UCAUUGCUU 2232 30 X CGAA AGCAAUGA ACAAGCCU 3847 UAGGCUUG CUGAUGAG 1532 CAUUGCUUA 2233 X CGAA AAGCAAUG CAAGCCUA 3855 AAGAUUCU CUGAUGAG 1533 ACAAGCCUA 2234 X CGAA AGGCUUGU AGAAUCUU WO 99/50403 PCT/US99/06507 131 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3861 UCUCUAAA CUGAUGAG 1534 CUAAGAAUC 2235 X CGAA AUUCUUAG UUUAGAGA 5 3863 CUUCUCUA CUGAUGAG 1535 AAGAAUCUU 2236 X CGAA AGAUUCUU UAGAGAAG 3864 ACUUCUCU CUGAUGAG 1536 AGAAUCUUU 2237 X CGAA AAGAUUCU AGAGAAGU 3865 UACUUCUC CUGAUGAG 1537 GAAUCUUUA 2238 10 X CGAA AAAGAUUC GAGAAGUA 3873 CUUAUGUA CUGAUGAG 1538 AGAGAAGUA 2239 X CGAA ACUUCUCU UACAUAAG 3875 AACUUAUG CUGAUGAG 1539 AGAAGUAUA 2240 X CGAA AUACUUCU CAUAAGUU 15 3879 CCUAAACU CUGAUGAG 1540 GUAUACAUA 2241 X CGAA AUGUAUAC AGUUUAGG 3883 UUAUCCUA CUGAUGAG 1541 ACAUAAGUU 2242 X CGAA ACUUAUGU UAGGAUAA 3884 UUUAUCCU CUGAUGAG 1542 CAUAAGUUU 2243 20 X CGAA AACUUAUG AGGAUAAA 3885 UUUUAUCC CUGAUGAG 1543 AUAAGUUUA 2244 X CGAA AAACUUAU GGAUAAAA 3890 CAUUAUUU CUGAUGAG 1544 UUUAGGAUA 2245 X CGAA AUCCUAAA AAAUAAUG 25 3895 AAUCCCAU CUGAUGAG 1545 GAUAAAAUA 2246 X CGAA AUUUUAUC AUGGGAUU 3903 GAAAAGAA CUGAUGAG 1546 AAUGGGAUU 2247 X CGAA AUCCCAUU UUCUUUUC 3904 AGAAAAGA CUGAUGAG 1547 AUGGGAUUU 2248 30 X CGAA AAUCCCAU UCUUUUCU 3905 AAGAAAAG CUGAUGAG 1548 UGGGAUUUU 2249 X CGAA AAAUCCCA CUUUUCUU 3906 AAAGAAAA CUGAUGAG 1549 GGGAUUUUC 2250 X CGAA AAAAUCCC UUUUCUUU WO 99/50403 PCT/US99/06507 132 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3908 GAAAAGAA CUGAUGAG 1550 GAUUUUCUU 2251 X CGAA AGAAAAUC UUCUUUUC 5 3909 AGAAAAGA CUGAUGAG 1551 AUUUUCUUU 2252 X CGAA AAGAAAAU UCUUUUCU 3910 GAGAAAAG CUGAUGAG 1552 UUUUCUUUU 2253 X CGAA AAAGAAAA CUUUUCUC 3911 AGAGAAAA CUGAUGAG 1553 UUUCUUUUC 2254 10 X CGAA AAAAGAAA UUUUCUCU 3913 CCAGAGAA CUGAUGAG 1554 UCUUUUCUU 2255 X CGAA AGAAAAGA UUCUCUGG 3914 ACCAGAGA CUGAUGAG 1555 CUUUUCUUU 2256 X CGAA AAGAAAAG UCUCUGGU 15 3915 UACCAGAG CUGAUGAG 1556 UUUUCUUUU 2257 X CGAA AAAGAAAA CUCUGGUA 3916 UUACCAGA CUGAUGAG 1557 UUUCUUUUC 2258 X CGAA AAAAGAAA UCUGGUAA 3918 UAUUACCA CUGAUGAG 1558 UCUUUUCUC 2259 20 X CGAA AGAAAAGA UGGUAAUA 3923 GUCAAUAU CUGAUGAG 1559 UCUCUGGUA 2260 X CGAA ACCAGAGA AUAUUGAC 3926 CAAGUCAA CUGAUGAG 1560 CUGGUAAUA 2261 X CGAA AUUACCAG UUGACUUG 25 3928 UACAAGUC CUGAUGAG 1561 GGUAAUAUU 2262 X CGAA AUAUUACC GACUUGUA 3933 AAAUAUAC CUGAUGAG 1562 UAUUGACUU 2263 X CGAA AGUCAAUA GUAUAUUU 3936 UUAAAAUA CUGAUGAG 1563 UGACUUGUA 2264 30 X CGAA ACAAGUCA UAUUUUAA 3938 UCUUAAAA CUGAUGAG 1564 ACUUGUAUA 2265 X CGAA AUACAAGU UUUUAAGA 3940 UUUCUUAA CUGAUGAG 1565 UUGUAUAUU 2266 X CGAA AUAUACAA UUAAGAAA WO 99/50403 PCT/US99/06507 133 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3941 AUUUCUUA CUGAUGAG 1566 UGUAUAUUU 2267 X CGAA AAUAUACA UAAGAAAU 5 3942 UAUUUCUU CUGAUGAG 1567 GUAUAUUUU 2268 X CGAA AAAUAUAC AAGAAAUA 3943 UUAUUUCU CUGAUGAG 1568 UAUAUUUUA 2269 X CGAA AAAAUAUA AGAAAUAA 3950 CUUUCUGU CUGAUGAG 1569 UAAGAAAUA 2270 10 X CGAA AUUUCUUA ACAGAAAG 3971 GUCUCCCA CUGAUGAG 1570 GGUGACAUU 2271 X CGAA AUGUCACC UGGGAGAC 3972 UGUCUCCC CUGAUGAG 1571 GUGACAUUU 2272 X CGAA AAUGUCAC GGGAGACA 15 3989 AAUAUAUA CUGAUGAG 1572 UGUGACAUU 2273 X CGAA AUGUCACA UAUAUAUU 3990 CAAUAUAU CUGAUGAG 1573 GUGACAUUU 2274 X CGAA AAUGUCAC AUAUAUUG 3991 UCAAUAUA CUGAUGAG 1574 UGACAUUUA 2275 20 X CGAA AAAUGUCA UAUAUUGA 3993 AUUCAAUA CUGAUGAG 1575 ACAUUUAUA 2276 X CGAA AUAAAUGU UAUUGAAU 3995 UAAUUCAA CUGAUGAG 1576 AUUUAUAUA 2277 X CGAA AUAUAAAU UUGAAUUA 25 3997 AUUAAUUC CUGAUGAG 1577 UUAUAUAUU 2278 X CGAA AUAUAUAA GAAUUAAU 4002 GGGAUAUU CUGAUGAG 1578 UAUUGAAUU 2279 X CGAA AUUCAAUA AAUAUCCC 4003 AGGGAUAU CUGAUGAG 1579 AUUGAAUUA 2280 30 X CGAA AAUUCAAU AUAUCCCU 4006 UGUAGGGA CUGAUGAG 1580 GAAUUAAUA 2281 X CGAA AUUAAUUC UCCCUACA 4008 CAUGUAGG CUGAUGAG 1581 AUUAAUAUC 2282 X CGAA AUAUUAAU CCUACAUG WO 99/50403 PCTIUS99/06507 134 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4012 AAUACAUG CUGAUGAG 1582 AUAUCCCUA 2283 X CGAA AGGGAUAU CAUGUAUU 5 4018 AUGUGCAA CUGAUGAG 1583 CUACAUGUA 2284 X CGAA ACAUGUAG UUGCACAU 4020 CAAUGUGC CUGAUGAG 1584 ACAUGUAUU 2285 X CGAA AUACAUGU GCACAUUG 4027 CUUUUUAC CUGAUGAG 1585 UUGCACAUU 2286 10 X CGAA AUGUGCAA GUAAAAAG 4030 AAACUUUU CUGAUGAG 1586 CACAUUGUA 2287 X CGAA ACAAUGUG AAAAGUUU 4037 AAAACUAA CUGAUGAG 1587 UAAAAAGUU 2288 X CGAA ACUUUUUA UUAGUUUU 15 4038 CAAAACUA CUGAUGAG 1588 AAAAAGUUU 2289 X CGAA AACUUUUU UAGUUUUG 4039 UCAAAACU CUGAUGAG 1589 AAAAGUUUU 2290 X CGAA AAACUUUU AGUUUUGA 4040 AUCAAAAC CUGAUGAG 1590 AAAGUUUUA 2291 20 X CGAA AAAACUUU GUUUUGAU 4043 CUCAUCAA CUGAUGAG 1591 GUUUUAGUU 2292 X CGAA ACUAAAAC UUGAUGAG 4044 ACUCAUCA CUGAUGAG 1592 UUUUAGUUU 2293 X CGAA AACUAAAA UGAUGAGU 25 4045 AACUCAUC CUGAUGAG 1593 UUUAGUUUU 2294 X CGAA AAACUAAA GAUGAGUU 4053 AAACUCAC CUGAUGAG 1594 UGAUGAGUU 2295 X CGAA ACUCAUCA GUGAGUUU 4060 ACAAGGUA CUGAUGAG 1595 UUGUGAGUU 2296 30 X CGAA ACUCACAA UACCUUGU 4061 UACAAGGU CUGAUGAG 1596 UGUGAGUUU 2297 X CGAA AACUCACA ACCUUGUA 4062 AUACAAGG CUGAUGAG 1597 GUGAGUUUA 2298 X CGAA AAACUCAC CCUUGUAU WO 99/50403 PCTIUS99/06507 135 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4066 CAGUAUAC CUGAUGAG 1598 GUUUACCUU 2299 X CGAA AGGUAAAC GUAUACUG 5 4069 CUACAGUA CUGAUGAG 1599 UACCUUGUA 2300 X CGAA ACAAGGUA UACUGUAG 4071 GCCUACAG CUGAUGAG 1600 CCUUGUAUA 2301 X CGAA AUACAAGG CUGUAGGC 4076 AGUGUGCC CUGAUGAG 1601 UAUACUGUA 2302 10 X CGAA ACAGUAUA GGCACACU 4085 UCAGUGCA CUGAUGAG 1602 GGCACACUU 2303 X CGAA AGUGUGCC UGCACUGA 4086 AUCAGUGC CUGAUGAG 1603 GCACACUUU 2304 X CGAA AAGUGUGC GCACUGAU 15 4095 UCAUGAUA CUGAUGAG 1604 GCACUGAUA 2305 X CGAA AUCAGUGC UAUCAUGA 4097 ACUCAUGA CUGAUGAG 1605 ACUGAUAUA 2306 X CGAA AUAUCAGU UCAUGAGU 4099 UCACUCAU CUGAUGAG 1606 UGAUAUAUC 2307 20 X CGAA AUAUAUCA AUGAGUGA 4110 AAGACAUU CUGAUGAG 1607 GAGUGAAUA 2308 X CGAA AUUCACUC AAUGUCUU 4116 GUAGGCAA CUGAUGAG 1608 AUAAAUGUC 2309 X CGAA ACAUUUAU UUGCCUAC 25 4118 GAGUAGGC CUGAUGAG 1609 AAAUGUCUU 2310 X CGAA AGACAUUU GCCUACUC 4123 UUUUUGAG CUGAUGAG 1610 UCUUGCCUA 2311 X CGAA AGGCAAGA CUCAAAAA 4126 UUUUUUUU CUGAUGAG 1611 UGCCUACUC 2312 30 X CGAA AGUAGGCA AAAAAAAA WO 99/50403 PCT/US99/06507 136 TABLE VI: HAIRPIN RIZOZYMES AND TRARGET SITES FOR TIE-2 Seq. Seq. I.D. Position RZ I.D. No. Substrate No. 10 AGAAGG AGAA GCAC ACCAGAGAAACA 2313 GUGCU GUU 2381 X GUACAUUACCUGGUA CCUUCU 5 76 AAACCC AGAA GUUU ACCAGAGAAACA 2314 AAACC GCU 2382 X GUACAUUACCUGGUA GGGUUU 164 GAACUA AGAA GGCU ACCAGAGAAACA 2315 AGCCA GCU 2383 X GUACAUUACCUGGUA UAGUUC 185 GGAGCA AGAA GACU ACCAGAGAAACA 2316 AGUCA GCU 2384 10 X GUACAUUACCUGGUA UGCUCC 256 UUCAGC AGAA GAUA ACCAGAGAAACA 2317 UAUCU GAU 2385 X GUACAUUACCUGGUA GCUGAA 360 ACUUCC AGAA GAUC ACCAGAGAAACA 2318 GAUCC GCU 2386 X GUACAUUACCUGGUA GGAAGU 15 681 GCAUGA AGAA GGUG ACCAGAGAAACA 2319 CACCU GCC 2387 X GUACAUUACCUGGUA UCAUGC 693 UCCUGG AGAA GAGC ACCAGAGAAACA 2320 GCUCA GCC 2388 X GUACAUUACCUGGUA CCAGGA 751 GGUGAA AGAA GAGG ACCAGAGAAACA 2321 CCUCG GCC 2389 20 X GUACAUUACCUGGUA UUCACC 818 AAGCAG AGAA GAGA ACCAGAGAAACA 2322 UCUCU GUA 2390 X GUACAUUACCUGGUA CUGCUU 823 CAUACA AGAA GUAC ACCAGAGAAACA 2323 GUACU GCU 2391 X GUACAUUACCUGGUA UGUAUG 25 986 CAGGGA AGAA GAAC ACCAGAGAAACA 2324 GUUCU GUC 2392 X GUACAUUACCUGGUA UCCCUG 994 AUAGGG AGAA GGGA ACCAGAGAAACA 2325 UCCCU GAC 2393 X GUACAUUACCUGGUA CCCUAU 30 1075 CUUACA AGAA GGCC ACCAGAGAAACA 2326 GGCCA GAU 2394 X GUACAUUACCUGGUA UGUAAG 1094 UGUUGC AGAA GCAC ACCAGAGAAACA 2327 GUGCA GCU 2395 X GUACAUUACCUGGUA GCAACA WO 99/50403 PCT/US99/06507 137 Seq. Seq. I.D. Position RZ I.D. No. Substrate No. 1139 CUGGAG AGAA GAGA ACCAGAGAAACA 2328 UCUCU GCU 2396 X GUACAUUACCUGGUA CUCCAG 5 1216 UAUAUG AGAA GGCA ACCAGAGAAACA 2329 UGCCA GAU 2397 X GUACAUUACCUGGUA CAUAUA 1312 UGUCCC AGAA GGCU ACCAGAGAAACA 2330 AGCCG GAU 2398 X GUACAUUACCUGGUA GGGACA 1351 GAAAUG AGAA GUAU ACCAGAGAAACA 2331 AUACG GAU 2399 10 X GUACAUUACCUGGUA CAUUUC 1363 UAUGGC AGAA GAGA ACCAGAGAAACA 2332 UCUCA GUA 2400 X GUACAUUACCUGGUA GCCAUA 1386 GGGAGG AGAA GGUG ACCAGAGAAACA 2333 CACCG GAU 2401 X GUACAUUACCUGGUA CCUCCC 15 1399 UCCUGA AGAA GGGG ACCAGAGAAACA 2334 CCCCU GAC 2402 X GUACAUUACCUGGUA UCAGGA 1544 GCUCAG AGAA GAUG ACCAGAGAAACA 2335 CAUCA GCU 2403 X GUACAUUACCUGGUA CUGAGC 1709 CUCCAC AGAA GACC ACCAGAGAAACA 2336 GGUCC GUC 2404 20 X GUACAUUACCUGGUA GUGGAG 1762 GAUAGA AGAA GUUG ACCAGAGAAACA 2337 CAACA GCU 2405 X GUACAUUACCUGGUA UCUAUC 1772 GAGGGA AGAA GAUA ACCAGAGAAACA 2338 UAUCG GAC 2406 X GUACAUUACCUGGUA UCCCUC 25 1803 CUUUUA AGAA GGAG ACCAGAGAAACA 2339 CUCCU GCC 2407 X GUACAUUACCUGGUA UAAAAG 1815 AGAGUG AGAA GACU ACCAGAGAAACA 2340 AGUCA GAC 2408 X GUACAUUACCUGGUA CACUCU 1977 ACCACG AGAA GCUC ACCAGAGAAACA 2341 GAGCA GUA 2409 30 X GUACAUUACCUGGUA CGUGGU 2038 GGUCCA AGAA GUGA ACCAGAGAAACA 2342 UCACU GCU 2410 X GUACAUUACCUGGUA UGGACC 2110 AAUCAC AGAA GAGG ACCAGAGAAACA 2343 CCUCG GCU 2411 X GUACAUUACCUGGUA GUGAUU WO 99/50403 PCT/US99/06507 138 Seq. Seq. I.D. Position RZ I.D. No. Substrate No. 2235 AGCUGA AGAA GAAU ACCAGAGAAACA 2344 AUUCA GUA 2412 X GUACAUUACCUGGUA UCAGCU 5 2241 CCCUUG AGAA GAUA ACCAGAGAAACA 2345 UAUCA GCU 2413 X GUACAUUACCUGGUA CAAGGG 2317 AGAAAA AGAA GGGU ACCAGAGAAACA 2346 ACCCA GCC 2414 X GUACAUUACCUGGUA UUUUCU 2365 UCCGAG AGAA GCUG ACCAGAGAAACA 2347 CAGCG GAC 2415 10 X GUACAUUACCUGGUA CUCGGA 2388 GCUAUA AGAA GCAU ACCAGAGAAACA 2348 AUGCU GCU 2416 X GUACAUUACCUGGUA UAUAGC 2410 CAUUCC AGAA GAGC ACCAGAGAAACA 2349 GCUCU GCU 2417 X GUACAUUACCUGGUA GGAAUG 15 2423 CAGUCA AGAA GGUC ACCAGAGAAACA 2350 GACCU GCC 2418 X GUACAUUACCUGGUA UGACUG 2427 AGCACA AGAA GGCA ACCAGAGAAACA 2351 UGCCU GAC 2419 X GUACAUUACCUGGUA UGUGCU 2436 AAGGCC AGAA GCAC ACCAGAGAAACA 2352 GUGCU GUU 2420 20 X GUACAUUACCUGGUA GGCCUU 2448 AAUAUG AGAA GAAA ACCAGAGAAACA 2353 UUUCU GAU 2421 X GUACAUUACCUGGUA CAUAUU 2524 CUGCAC AGAA GGUU ACCAGAGAAACA 2354 AACCA GCU 2422 X GUACAUUACCUGGUA GUGCAG 25 2532 GAGUUG AGAA GCAC ACCAGAGAAACA 2355 GUGCA GUU 2423 X GUACAUUACCUGGUA CAACUC 2581 UGUAGG AGAA GGGU ACCAGAGAAACA 2356 ACCCA GAU 2424 X GUACAUUACCUGGUA CCUACA 2694 GCAUCC AGAA GUAA ACCAGAGAAACA 2357 UUACG GAU 2425 30 X GUACAUUACCUGGUA GGAUGC 2914 UGCUGG AGAA GUCU ACCAGAGAAACA 2358 AGACG GAC 2426 X GUACAUUACCUGGUA CCAGCA 2955 UGGGAG AGAA GUGU ACCAGAGAAACA 2359 ACACU GUC 2427 X GUACAUUACCUGGUA CUCCCA WO 99/50403 PCTIUS99/06507 139 Seq. Seq. I.D. Position RZ I.D. No. Substrate No. 2967 UGAAGG AGAA GCUG ACCAGAGAAACA 2360 CAGCA GCU 2428 X GUACAUUACCUGGUA CCUUCA 5 2983 CACGUC AGAA GCGA ACCAGAGAAACA 2361 UCGCU GCC 2429 X GUACAUUACCUGGUA GACGUG 2986 GGCCAC AGAA GCAG ACCAGAGAAACA 2362 CUGCC GAC 2430 X GUACAUUACCUGGUA GUGGCC 3024 UGGAUA AGAA GUUU ACCAGAGAAACA 2363 AAACA GUU 2431 10 X GUACAUUACCUGGUA UAUCCA 3091 UCCAAA AGAA GCUA ACCAGAGAAACA 2364 UAGCA GAU 2432 X GUACAUUACCUGGUA UUUGGA 3300 CCCUGG AGAA GCUU ACCAGAGAAACA 2365 AAGCU GCC 2433 X GUACAUUACCUGGUA CCAGGG 15 3314 UCUCCA AGAA GUAG ACCAGAGAAACA 2366 CUACA GAC 2434 X GUACAUUACCUGGUA UGGAGA 3500 CAGCAG AGAA GUCA ACCAGAGAAACA 2367 UGACU GUU 2435 X GUACAUUACCUGGUA CUGCUG 3505 UUCUUC AGAA GAAC ACCAGAGAAACA 2368 GUUCU GCU 2436 20 X GUACAUUACCUGGUA GAAGAA 3517 GUCCUA AGAA GCUU ACCAGAGAAACA 2369 AAGCG GCC 2437 X GUACAUUACCUGGUA UAGGAC 3535 AGGGUA AGAA GAUG ACCAGAGAAACA 2370 CAUCUS GUA 2438 X GUACAUUACCUGGUA UACCCU 25 3546 AAGGGA AGAA GAGG ACCAGAGAAACA 2371 CCUCU GUU 2439 X GUACAUUACCUGGUA UCCCUU 3583 UUUCUC AGAA GUUG ACCAGAGAAACA 2372 CAACU GCU 2440 X GUACAUUACCUGGUA GAGAAA 3700 AGAAGA AGAA GAUU ACCAGAGAAACA 2373 AAUCA GAU 2441 30 X GUACAUUACCUGGUA UCUUCU 3730 GCAUGC AGAA GGUG ACCAGAGAAACA 2374 CACCU GUA 2442 X GUACAUUACCUGGUA GCAUGC 3741 AAACGG AGAA GGCA ACCAGAGAAACA 2375 UGCCA GUC 2443 X GUACAUUACCUGGUA CCGUUU WO 99/50403 PCTIUS99/06507 140 Seq. Seq. I.D. Position RZ I.D. No. Substrate No. 3746 AAAUGA AGAA GGAC ACCAGAGAAACA 2376 GUCCC GUU 2444 X GUACAUUACCUGGUA UCAUUU 5 3772 ACACAA AGAA GAGU ACCAGAGAAACA 2377 ACUCU GUC 2445 X GUACAUUACCUGGUA UUGUGU 3788 CUUGCA AGAA GUGG ACCAGAGAAACA 2378 CCACA GCC 2446 X GUACAUUACCUGGUA UGCAAG 3801 AUCCUG AGAA GAAC ACCAGAGAAACA 2379 GUUCA GUC 2447 10 X GUACAUUACCUGGUA CAGGAU 4073 UGUGCC AGAA GUAU ACCAGAGAAACA 2380 AUACU GUA 2448 X GUACAUUACCUGGUA GGCACA 15 20 25 30 WO 99/50403 PCT/US99/06507 141 TABLE VII: HAMMERHEAD RIBOZYME AND TARGET SITE SEQUENCES FOR INTEGRIN ALPHA 6 SUBUNIT Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 11 ACCCCCGG CUGAUGAG X 2449 GCGACCGUC 3588 CGAA ACGGUCGC CCGGGGGU 5 63 GCUGCUGC CUGAUGAG X 2450 GCUGCGGUA 3589 CGAA ACCGCAGC GCAGCAGC 82 CUGGGUCC CUGAUGAG X 2451 GGCAGCCUC 3590 CGAA AGGCUGCC GGACCCAG 119 GGAGCGGG CUGAUGAG X 2452 CUGCAGGUC 3591 10 CGAA ACCUGCAG CCCGCUCC 126 GGGGAGGG CUGAUGAG X 2453 UCCCCGCUC 3592 CGAA AGCGGGGA CCCUCCCC 131 CGCACGGG CUGAUGAG X 2454 GCUCCCCUC 3593 CGAA AGGGGAGC CCCGUGCG 15 141 CAUGGGCG CUGAUGAG X 2455 CCGUGCGUC 3594 CGAA ACGCACGG CGCCCAUG 172 GGUAGAGC CUGAUGAG X 2456 GCUGUGCUU 3595 CGAA AGCACAGC GCUCUACC 176 GACAGGUA CUGAUGAG X 2457 UGCUUGCUC 3596 20 CGAA AGCAAGCA UACCUGUC 178 CCGACAGG CUGAUGAG X 2458 CUUGCUCUA 3597 CGAA AGAGCAAG CCUGUCGG 184 GCCCCGCC CUGAUGAG X 2459 CUACCUGUC 3598 CGAA ACAGGUAG GGCGGGGC 25 194 CGGGACAG CUGAUGAG X 2460 GCGGGGCUC 3599 CGAA AGCCCCGC CUGUCCCG 199 CGAGCCGG CUGAUGAG X 2461 GCUCCUGUC 3600 CGAA ACAGGAGC CCGGCUCG 206 GCUGCGCC CUGAUGAG X 2462 UCCCGGCUC 3601 30 CGAA AGCCGGGA GGCGCAGC 217 CCAAGUUG CUGAUGAG X 2463 CGCAGCCUU 3602 CGAA AGGCUGCG CAACUUGG WO 99/50403 PCTIUS99/06507 142 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 218 UCCAAGUU CUGAUGAG X 2464 GCAGCCUUC 3603 CGAA AAGGCUGC AACUUGGA 5 223 GAGUGUCC CUGAUGAG X 2465 CUUCAACUU 3604 CGAA AGUUGAAG GGACACUC 231 GUCCUCCC CUGAUGAG X 2466 UGGACACUC 3605 CGAA AGUGUCCA GGGAGGAC 248 UAUUUCCG CUGAUGAG X 2467 AACGUGAUC 3606 10 CGAA AUCACGUU CGGAAAUA 256 GGUCUCCA CUGAUGAG X 2468 CCGGAAAUA 3607 CGAA AUUUCCGG UGGAGACC 275 AAGCCGAA CUGAUGAG X 2469 GGGAGCCUC 3608 CGAA AGGCUCCC UUCGGCUU 15 277 AGAAGCCG CUGAUGAG X 2470 GAGCCUCUU 3609 CGAA AGAGGCUC CGGCUUCU 278 GAGAAGCC CUGAUGAG X 2471 AGCCUCUUC 3610 CGAA AAGAGGCU GGCUUCUC 283 CCAGCGAG CUGAUGAG X 2472 CUUCGGCUU 3611 20 CGAA AGCCGAAG CUCGCUGG 284 GCCAGCGA CUGAUGAG X 2473 UUCGGCUUC 3612 CGAA AAGCCGAA UCGCUGGC 286 UGGCCAGC CUGAUGAG X 2474 CGGCUUCUC 3613 CGAA AGAAGCCG GCUGGCCA 25 331 CCACGAGC CUGAUGAG X 2475 GCGGCUGUU 3614 CGAA ACAGCCGC GCUCGUGG 335 GCCCCCAC CUGAUGAG X 2476 CUGUUGCUC 3615 CGAA AGCAACAG GUGGGGGC 362 UGCAGUGG CUGAUGAG X 2477 GAAGCGCUU 3616 30 CGAA AGCGCUUC CCACUGCA 363 CUGCAGUG CUGAUGAG X 2478 AAGCGCUUC 3617 CGAA AAGCGCUU CACUGCAG 397 CGCAGCUG CUGAUGAG X 2479 AGGGCUGUA 3618 CGAA ACAGCCCU CAGCUGCG WO 99/50403 PCT/US99/06507 143 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 410 CGGGCGGU CUGAUGAG X 2480 UGCGACAUC 3619 CGAA AUGUCGCA ACCGCCCG 5 437 UCAAACUC CUGAUGAG X 2481 ACGCGGAUC 3620 CGAA AUCCGCGU GAGUUUGA 442 CGUUAUCA CUGAUGAG X 2482 GAUCGAGUU 3621 CGAA ACUCGAUC UGAUAACG 443 UCGUUAUC CUGAUGAG X 2483 AUCGAGUUU 3622 10 CGAA AACUCGAU GAUAACGA 447 AGCAUCGU CUGAUGAG X 2484 AGUUUGAUA 3623 CGAA AUCAAACU ACGAUGCU 466 UGCUUUCU CUGAUGAG X 2485 CCCCACGUC 3624 CGAA ACGUGGGG AGAAAGCA 15 483 CAUCCACU CUGAUGAG X 2486 AGGAAGAUC 3625 CGAA AUCUUCCU AGUGGAUG 497 UGGACGGU CUGAUGAG X 2487 AUGGGGGUC 3626 CGAA ACCCCCAU ACCGUCCA 503 UGGCUCUG CUGAUGAG X 2488 GUCACCGUC 3627 20 CGAA ACGGUGAC CAGAGCCA 516 GCCCCCUG CUGAUGAG X 2489 GCCAAGGUC 3628 CGAA ACCUUGGC CAGGGGGC 530 CAUGUCAC CUGAUGAG X 2490 GGCAAGGUC 3629 CGAA ACCUUGCC GUGACAUG 25 543 AUAUCGGU CUGAUGAG X 2491 CAUGUGCUC 3630 CGAA AGCACAUG ACCGAUAU 550 UUUUUUCA CUGAUGAG X 2492 UCACCGAUA 3631 CGAA AUCGGUGA UGAAAAAA 569 UUCGUAUU CUGAUGAG X 2493 CAGCAUGUU 3632 30 CGAA ACAUGCUG AAUACGAA 570 CUUCGUAU CUGAUGAG X 2494 AGCAUGUUA 3633 CGAA AACAUGCU AUACGAAG 573 CUGCUUCG CUGAUGAG X 2495 AUGUUAAUA 3634 CGAA AUUAACAU CGAAGCAG WO 99/50403 PCT/US99/06507 144 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 586 UGUCUCGG CUGAUGAG X 2496 GCAGGAAUC 3635 CGAA AUUCCUGC CCGAGACA 5 596 CGCCCAAA CUGAUGAG X 2497 CGAGACAUC 3636 CGAA AUGUCUCG UUUGGGCG 598 ACCGCCCA CUGAUGAG X 2498 AGACAUCUU 3637 CGAA AGAUGUCU UGGGCGGU 599 CACCGCCC CUGAUGAG X 2499 GACAUCUUU 3638 10 CGAA AAGAUGUC GGGCGGUG 609 CAGGACAU CUGAUGAG X 2500 GGCGGUGUU 3639 CGAA ACACCGCC AUGUCCUG 610 UCAGGACA CUGAUGAG X 2501 GCGGUGUUA 3640 CGAA AACACCGC UGUCCUGA 15 614 UGACUCAG CUGAUGAG X 2502 UGUUAUGUC 3641 CGAA ACAUAACA CUGAGUCA 621 GAGAUUCU CUGAUGAG X 2503 UCCUGAGUC 3642 CGAA ACUCAGGA AGAAUCUC 627 AAUCCUGA CUGAUGAG X 2504 GUCAGAAUC 3643 20 CGAA AUUCUGAC UCAGGAUU 629 UCAAUCCU CUGAUGAG X 2505 CAGAAUCUC 3644 CGAA AGAUUCUG AGGAUUGA 635 UCGUCUUC CUGAUGAG X 2506 CUCAGGAUU 3645 CGAA AUCCUGAG GAAGACGA 25 645 CCCAUCCA CUGAUGAG X 2507 AAGACGAUA 3646 CGAA AUCGUCUU UGGAUGGG 660 AAAGCUCC CUGAUGAG X 2508 GGGGAGAUU 3647 CGAA AUCUCCCC GGAGCUUU 667 CAUCACAA CUGAUGAG X 2509 UUGGAGCUU 3648 30 CGAA AGCUCCAA UUGUGAUG 668 CCAUCACA CUGAUGAG X 2510 UGGAGCUUU 3649 CGAA AAGCUCCA UGUGAUGG 669 CCCAUCAC CUGAUGAG X 2511 GGAGCUUUU 3650 CGAA AAAGCUCC GUGAUGGG WO 99/50403 PCTIUS99/06507 145 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 682 GGCCUCUC CUGAUGAG X 2512 UGGGCGAUU 3651 CGAA AUCGCCCA GAGAGGCC 5 700 AAGAGCCA CUGAUGAG X 2513 UGAGAAAUU 3652 CGAA AUUUCUCA UGGCUCUU 701 CAAGAGCC CUGAUGAG X 2514 GAGAAAUUU 3653 CGAA AAUUUCUC GGCUCUUG 706 GCUGGCAA CUGAUGAG X 2515 AUUUGGCUC 3654 10 CGAA AGCCAAAU UUGCCAGC 708 UUGCUGGC CUGAUGAG X 2516 UUGGCUCUU 3655 CGAA AGAGCCAA GCCAGCAA 722 GUAGCUGC CUGAUGAG X 2517 CAAGGUGUA 3656 CGAA ACACCUUG GCAGCUAC 15 729 AGUAAAAG CUGAUGAG X 2518 UAGCAGCUA 3657 CGAA AGCUGCUA CUUUUACU 732 UUUAGUAA CUGAUGAG X 2519 CAGCUACUU 3658 CGAA AGUAGCUG UUACUAAA 733 CUUUAGUA CUGAUGAG X 2520 AGCUACUUU 3659 20 CGAA AAGUAGCU UACUAAAG 734 UCUUUAGU CUGAUGAG X 2521 GCUACUUUU 3660 CGAA AAAGUAGC ACUAAAGA 735 GUCUUUAG CUGAUGAG X 2522 CUACUUUUA 3661 CGAA AAAAGUAG CUAAAGAC 25 738 AAAGUCUU CUGAUGAG X 2523 CUUUUACUA 3662 CGAA AGUAAAAG AAGACUUU 745 UGUAAUGA CUGAUGAG X 2524 UAAAGACUU 3663 CGAA AGUCUUUA UCAUUACA 746 AUGUAAUG CUGAUGAG X 2525 AAAGACUUU 3664 30 CGAA AAGUCUUU CAUUACAU 747 AAUGUAAU CUGAUGAG X 2526 AAGACUUUC 3665 CGAA AAAGUCUU AUUACAUU 750 UACAAUGU CUGAUGAG X 2527 ACUUUCAUU 3666 CGAA AUGAAAGU ACAUUGUA WO 99/50403 PCT/US99/06507 146 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 751 AUACAAUG CUGAUGAG X 2528 CUUUCAUUA 3667 CGAA AAUGAAAG CAUUGUAU 5 755 CCAAAUAC CUGAUGAG X 2529 CAUUACAUU 3668 CGAA AUGUAAUG GUAUUUGG 758 GCUCCAAA CUGAUGAG X 2530 UACAUUGUA 3669 CGAA ACAAUGUA UUUGGAGC 760 GGGCUCCA CUGAUGAG X 2531 CAUUGUAUU 3670 10 CGAA AUACAAUG UGGAGCCC 761 GGGGCUCC CUGAUGAG X 2532 AUUGUAUUU 3671 CGAA AAUACAAU GGAGCCCC 774 GUUAUAAG CUGAUGAG X 2533 CCCCGGGUA 3672 CGAA ACCCGGGG CUUAUAAC 15 777 CCAGUUAU CUGAUGAG X 2534 CGGGUACUU 3673 CGAA AGUACCCG AUAACUGG 778 UCCAGUUA CUGAUGAG X 2535 GGGUACUUA 3674 CGAA AAGUACCC UAACUGGA 780 UUUCCAGU CUGAUGAG X 2536 GUACUUAUA 3675 20 CGAA AUAAGUAC ACUGGAAA 794 ACACGAAC CUGAUGAG X 2537 AAAGGGAUU 3676 CGAA AUCCCUUU GUUCGUGU 797 UCUACACG CUGAUGAG X 2538 GGGAUUGUU 3677 CGAA ACAAUCCC CGUGUAGA 25 798 CUCUACAC CUGAUGAG X 2539 GGAUUGUUC 3678 CGAA AACAAUCC GUGUAGAG 803 UUUUGCUC CUGAUGAG X 2540 GUUCGUGUA 3679 CGAA ACACGAAC GAGCAAAA 816 AAAAGUGU CUGAUGAG X 2541 AAAAGAAUA 3680 30 CGAA AUUCUUUU ACACUUUU 822 GUCAAAAA CUGAUGAG X 2542 AUAACACUU 3681 CGAA AGUGUUAU UUUUUGAC 823 UGUCAAAA CUGAUGAG X 2543 UAACACUUU 3682 CGAA AAGUGUUA UUUUGACA WO 99/50403 PCTIUS99/06507 147 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 824 AUGUCAAA CUGAUGAG X 2544 AACACUUUU 3683 CGAA AAAGUGUU UUUGACAU 5 825 CAUGUCAA CUGAUGAG X 2545 ACACUUUUU 3684 CGAA AAAAGUGU UUGACAUG 826 UCAUGUCA CUGAUGAG X 2546 CACUUUUUU 3685 CGAA AAAAAGUG UGACAUGA 827 UUCAUGUC CUGAUGAG X 2547 ACUUUUUUU 3686 10 CGAA AAAAAAGU GACAUGAA 839 UCUUCAAA CUGAUGAG X 2548 AUGAACAUC 3687 CGAA AUGUUCAU UUUGAAGA 841 CAUCUUCA CUGAUGAG X 2549 GAACAUCUU 3688 CGAA AGAUGUUC UGAAGAUG 15 842 CCAUCUUC CUGAUGAG X 2550 AACAUCUUU 3689 CGAA AAGAUGUU GAAGAUGG 855 AACUUCAU CUGAUGAG X 2551 AUGGGCCUU 3690 CGAA AGGCCCAU AUGAAGUU 856 CAACUUCA CUGAUGAG X 2552 UGGGCCUUA 3691 20 CGAA AAGGCCCA UGAAGUUG 863 UCUCCACC CUGAUGAG X 2553 UAUGAAGUU 3692 CGAA ACUUCAUA GGUGGAGA 891 AGGAACGA CUGAUGAG X 2554 AUGAAAGUC 3693 CGAA ACUUUCAU UCGUUCCU 25 893 ACAGGAAC CUGAUGAG X 2555 GAAAGUCUC 3694 CGAA AGACUUUC GUUCCUGU 896 GGAACAGG CUGAUGAG X 2556 AGUCUCGUU 3695 CGAA ACGAGACU CCUGUUCC 897 AGGAACAG CUGAUGAG X 2557 GUCUCGUUC 3696 30 CGAA AACGAGAC CUGUUCCU 902 UUAGCAGG CUGAUGAG X 2558 GUUCCUGUU 3697 CGAA ACAGGAAC CCUGCUAA 903 GUUAGCAG CUGAUGAG X 2559 UUCCUGUUC 3698 CGAA AACAGGAA CUGCUAAC WO 99/50403 PCT/US99/06507 148 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 909 GUAACUGU CUGAUGAG X 2560 UUCCUGCUA 3699 CGAA AGCAGGAA ACAGUUAC 5 915 ACCUAAGU CUGAUGAG X 2561 CUAACAGUU 3700 CGAA ACUGUUAG ACUUAGGU 916 AACCUAAG CUGAUGAG X 2562 UAACAGUUA 3701 CGAA AACUGUUA CUUAGGUU 919 AAAAACCU CUGAUGAG X 2563 CAGUUACUU 3702 10 CGAA AGUAACUG AGGUUUUU 920 GAAAAACC CUGAUGAG X 2564 AGUUACUUA 3703 CGAA AAGUAACU GGUUUUUC 924 CAAAGAAA CUGAUGAG X 2565 ACUUAGGUU 3704 CGAA ACCUAAGU UUUCUUUG 15 925 CCAAAGAA CUGAUGAG X 2566 CUUAGGUUU 3705 CGAA AACCUAAG UUCUUUGG 926 UCCAAAGA CUGAUGAG X 2567 UUAGGUUUU 3706 CGAA AAACCUAA UCUUUGGA 927 GUCCAAAG CUGAUGAG X 2568 UAGGUUUUU 3707 20 CGAA AAAACCUA CUUUGGAC 928 AGUCCAAA CUGAUGAG X 2569 AGGUUUUUC 3708 CGAA AAAAACCU UUUGGACU 930 UGAGUCCA CUGAUGAG X 2570 GUUUUUCUU 3709 CGAA AGAAAAAC UGGACUCA 25 931 CUGAGUCC CUGAUGAG X 2571 UUUUUCUUU 3710 CGAA AAGAAAAA GGACUCAG 937 CUUUCCCU CUGAUGAG X 2572 UUUGGACUC 3711 CGAA AGUCCAAA AGGGAAAG 948 AGAAACAA CUGAUGAG X 2573 GGAAAGGUA 3712 30 CGAA ACCUUUCC UUGUUUCU 950 UUAGAAAC CUGAUGAG X 2574 AAAGGUAUU 3713 CGAA AUACCUUU GUUUCUAA 953 UCUUUAGA CUGAUGAG X 2575 GGUAUUGUU 3714 CGAA ACAAUACC UCUAAAGA WO 99/50403 PCT/US99/06507 149 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 954 AUCUUUAG CUGAUGAG X 2576 GUAUUGUUU 3715 CGAA AACAAUAC CUAAAGAU 955 CAUCUUUA CUGAUGAG X 2577 UAUUGUUUC 3716 CGAA AAACAAUA UAAAGAUG 957 CUCAUCUU CUGAUGAG X 2578 UUGUUUCUA 3717 CGAA AGAAACAA AAGAUGAG 968 ACAAAAGU CUGAUGAG X 2579 GAUGAGAUC 3718 1.0 CGAA AUCUCAUC ACUUUUGU 972 AGAUACAA CUGAUGAG X 2580 AGAUCACUU 3719 CGAA AGUGAUCU UUGUAUCU 973 CAGAUACA CUGAUGAG X 2581 GAUCACUUU 3720 CGAA AAGUGAUC UGUAUCUG L5 974 CCAGAUAC CUGAUGAG X 2582 AUCACUUUU 3721 CGAA AAAGUGAU GUAUCUGG 977 GCACCAGA CUGAUGAG X 2583 ACUUUUGUA 3722 CGAA ACAAAAGU UCUGGUGC 979 GAGCACCA CUGAUGAG X 2584 UUUUGUAUC 3723 20 CGAA AUACAAAA UGGUGCUC 987 GGCUCUGG CUGAUGAG X 2585 CUGGUGCUC 3724 CGAA AGCACCAG CCAGAGCC 999 UCCACUGU CUGAUGAG X 2586 GAGCCAAUC 3725 CGAA AUUGGCUC ACAGUGGA ?5 1016 UUCAGCAA CUGAUGAG X 2587 GCCGUGGUU 3726 CGAA ACCACGGC UUGCUGAA 1017 CUUCAGCA CUGAUGAG X 2588 CCGUGGUUU 3727 CGAA AACCACGG UGCUGAAG 1018 UCUUCAGC CUGAUGAG X 2589 CGUGGUUUU 3728 CGAA AAACCACG GCUGAAGA 1039 GAUGUGCA CUGAUGAG X 2590 CAUGAAGUC 3729 CGAA ACUUCAUG UGCACAUC 1047 AGGGAGGA CUGAUGAG X 2591 CUGCACAUC 3730 CGAA AUGUGCAG UCCUCCCU WO 99/50403 PCT/US99/06507 150 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1049 UCAGGGAG CUGAUGAG X 2592 GCACAUCUC 3731 CGAA AGAUGUGC CUCCCUGA 5 1052 UGCUCAGG CUGAUGAG X 2593 CAUCUCCUC 3732 CGAA AGGAGAUG CCUGAGCA 1064 CCAUCGAA CUGAUGAG X 2594 GAGCACAUA 3733 CGAA AUGUGCUC UUCGAUGG 1066 CUCCAUCG CUGAUGAG X 2595 GCACAUAUU 3734 10 CGAA AUAUGUGC CGAUGGAG 1067 UCUCCAUC CUGAUGAG X 2596 CACAUAUUC 3735 CGAA AAUAUGUG GAUGGAGA 1080 AGAGGCCA CUGAUGAG X 2597 GAGAAGGUC 3736 CGAA ACCUUCUC UGGCCUCU 15 1087 CAAAUGAA CUGAUGAG X 2598 UCUGGCCUC 3737 CGAA AGGCCAGA UUCAUUUG 1089 GCCAAAUG CUGAUGAG X 2599 UGGCCUCUU 3738 CGAA AGAGGCCA CAUUUGGC 1090 AGCCAAAU CUGAUGAG X 2600 GGCCUCUUC 3739 20 CGAA AAGAGGCC AUUUGGCU 1093 CAUAGCCA CUGAUGAG X 2601 CUCUUCAUU 3740 CGAA AUGAAGAG UGGCUAUG 1094 UCAUAGCC CUGAUGAG X 2602 UCUUCAUUU 3741 CGAA AAUGAAGA GGCUAUGA 25 1099 CCACAUCA CUGAUGAG X 2603 AUUUGGCUA 3742 CGAA AGCCAAAU UGAUGUGG 1121 UCCUUGUU CUGAUGAG X 2604 GUGGACCUC 3743 CGAA AGGUCCAC AACAAGGA 1143 AAUAACUA CUGAUGAG X 2605 GGCAAGAUA 3744 30 CGAA AUCUUGCC UAGUUAUU 1145 CCAAUAAC CUGAUGAG X 2606 CAAGAUAUA 3745 CGAA AUAUCUUG GUUAUUGG 1148 GCUCCAAU CUGAUGAG X 2607 GAUAUAGUU 3746 CGAA ACUAUAUC AUUGGAGC WO 99/50403 PCTIUS99/06507 151 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1149 GGCUCCAA CUGAUGAG X 2608 AUAUAGUUA 3747 CGAA AACUAUAU UUGGAGCC 5 1151 GGGGCUCC CUGAUGAG X 2609 AUAGUUAUU 3748 CGAA AUAACUAU GGAGCCCC 1165 UAUCAAAA CUGAUGAG X 2610 CCCACAGUA 3749 CGAA ACUGUGGG UUUUGAUA 1167 UCUAUCAA CUGAUGAG X 2611 CACAGUAUU 3750 10 CGAA AUACUGUG UUGAUAGA 1168 CUCUAUCA CUGAUGAG X 2612 ACAGUAUUU 3751 CGAA AAUACUGU UGAUAGAG 1169 UCUCUAUC CUGAUGAG X 2613 CAGUAUUUU 3752 CGAA AAAUACUG GAUAGAGA 15 1173 UCCAUCUC CUGAUGAG X 2614 AUUUUGAUA 3753 CGAA AUCAAAAU GAGAUGGA 1187 GCACCUCC CUGAUGAG X 2615 GGAGAAGUU 3754 CGAA ACUUCUCC GGAGGUGC 1201 UGUAGACA CUGAUGAG X 2616 UGCAGUGUA 3755 20 CGAA ACACUGCA UGUCUACA 1205 UUCAUGUA CUGAUGAG X 2617 GUGUAUGUC 3756 CGAA ACAUACAC UACAUGAA 1207 GGUUCAUG CUGAUGAG X 2618 GUAUGUCUA 3757 CGAA AGACAUAC CAUGAACC 25 1233 CUUCACAU CUGAUGAG X 2619 GAUGGAAUA 3758 CGAA AUUCCAUC AUGUGAAG 1247 UUAAGACG CUGAUGAG X 2620 AAGCCAAUU 3759 CGAA AUUGGCUU CGUCUUAA 1248 AUUAAGAC CUGAUGAG X 2621 AGCCAAUUC 3760 30 CGAA AAUUGGCU GUCUUAAU 1251 UCCAUUAA CUGAUGAG X 2622 CAAUUCGUC 3761 CGAA ACGAAUUG UUAAUGGA 1253 GUUCCAUU CUGAUGAG X 2623 AUUCGUCUU 3762 CGAA AGACGAAU AAUGGAAC WO 99/50403 PCTIUS99/06507 152 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1254 GGUUCCAU CUGAUGAG X 2624 UUCGUCUUA 3763 CGAA AAGACGAA AUGGAACC 5 1269 AAACAUAG CUGAUGAG X 2625 CCAAAGAUU 3764 CGAA AUCUUUGG CUAUGUUU 1270 CAAACAUA CUGAUGAG X 2626 CAAAGAUUC 3765 CGAA AAUCUUUG UAUGUUUG 1272 GCCAAACA CUGAUGAG X 2627 AAGAUUCUA 3766 10 CGAA AGAAUCUU UGUUUGGC 1276 CAAUGCCA CUGAUGAG X 2628 UUCUAUGUU 3767 CGAA ACAUAGAA UGGCAUUG 1277 GCAAUGCC CUGAUGAG X 2629 UCUAUGUUU 3768 CGAA AACAUAGA GGCAUUGC 15 1283 UUUACUGC CUGAUGAG X 2630 UUUGGCAUU 3769 CGAA AUGCCAAA GCAGUAAA 1289 AUAUUUUU CUGAUGAG X 2631 AUUGCAGUA 3770 CGAA ACUGCAAU AAAAAUAU 1296 AUCUCCAA CUGAUGAG X 2632 UAAAAAAUA 3771 20 CGAA AUUUUUUA UUGGAGAU 1298 AUAUCUCC CUGAUGAG X 2633 AAAAAUAUU 3772 CGAA AUAUUUUU GGAGAUAU 1305 UUGAUUAA CUGAUGAG X 2634 UUGGAGAUA 3773 CGAA AUCUCCAA UUAAUCAA 25 1307 UCUUGAUU CUGAUGAG X 2635 GGAGAUAUU 3774 CGAA AUAUCUCC AAUCAAGA 1308 AUCUUGAU CUGAUGAG X 2636 GAGAUAUUA 3775 CGAA AAUAUCUC AUCAAGAU 1311 GCCAUCUU CUGAUGAG X 2637 AUAUUAAUC 3776 30 CGAA AUUAAUAU AAGAUGGC 1321 UAUCUGGG CUGAUGAG X 2638 AGAUGGCUA 3777 CGAA AGCCAUCU CCCAGAUA 1329 AACUGCAA CUGAUGAG X 2639 ACCCAGAUA 3778 CGAA AUCUGGGU UUGCAGUU WO 99/50403 PCTIUS99/06507 153 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1331 CCAACUGC CUGAUGAG X 2640 CCAGAUAUU 3779 CGAA AUAUCUGG GCAGUUGG 5 1337 GGAGCUCC CUGAUGAG X 2641 AUUGCAGUU 3780 CGAA ACUGCAAU GGAGCUCC 1344 AUCAUACG CUGAUGAG X 2642 UUGGAGCUC 3781 CGAA AGCUCCAA CGUAUGAU 1348 AGUCAUCA CUGAUGAG X 2643 AGCUCCGUA 3782 10 CGAA ACGGAGCU UGAUGACU 1357 CCUUUCCC CUGAUGAG X 2644 UGAUGACUU 3783 CGAA AGUCAUCA GGGAAAGG 1367 UAGAUAAA CUGAUGAG X 2645 GGAAAGGUU 3784 CGAA ACCUUUCC UUUAUCUA 15 1368 AUAGAUAA CUGAUGAG X 2646 GAAAGGUUU 3785 CGAA AACCUUUC UUAUCUAU 1369 GAUAGAUA CUGAUGAG X 2647 AAAGGUUUU 3786 CGAA AAACCUUU UAUCUAUC 1370 UGAUAGAU CUGAUGAG X 2648 AAGGUUUUU 3787 20 CGAA AAAACCUU AUCUAUCA 1371 AUGAUAGA CUGAUGAG X 2649 AGGUUUUUA 3788 CGAA AAAAACCU UCUAUCAU 1373 CCAUGAUA CUGAUGAG X 2650 GUUUUUAUC 3789 CGAA AUAAAAAC UAUCAUGG 25 1375 AUCCAUGA CUGAUGAG X 2651 UUUUAUCUA 3790 CGAA AGAUAAAA UCAUGGAU 1377 AGAUCCAU CUGAUGAG X 2652 UUAUCUAUC 3791 CGAA AUAGAUAA AUGGAUCU 1384 CAUUUGCA CUGAUGAG X 2653 UCAUGGAUC 3792 30 CGAA AUCCAUGA UGCAAAUG 1397 UUGGUAUU CUGAUGAG X 2654 AAUGGAAUA 3793 CGAA AUUCCAUU AAUACCAA 1401 UGGUUUGG CUGAUGAG X 2655 GAAUAAAUA 3794 CGAA AUUUAUUC CCAAACCA WO 99/50403 PCT/US99/06507 154 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1418 CCCUUGAG CUGAUGAG X 2656 ACACAGGUU 3795 CGAA ACCUGUGU CUCAAGGG 5 1419 ACCCUUGA CUGAUGAG X 2657 CACAGGUUC 3796 CGAA AACCUGUG UCAAGGGU 1421 AUACCCUU CUGAUGAG X 2658 CAGGUUCUC 3797 CGAA AGAACCUG AAGGGUAU 1428 AGGUGAUA CUGAUGAG X 2659 UCAAGGGUA 3798 10 CGAA ACCCUUGA UAUCACCU 1430 UAAGGUGA CUGAUGAG X 2660 AAGGGUAUA 3799 CGAA AUACCCUU UCACCUUA 1432 AAUAAGGU CUGAUGAG X 2661 GGGUAUAUC 3800 CGAA AUAUACCC ACCUUAUU 15 1437 UCCAAAAU CUGAUGAG X 2662 UAUCACCUU 3801 CGAA AGGUGAUA AUUUUGGA 1438 AUCCAAAA CUGAUGAG X 2663 AUCACCUUA 3802 CGAA AAGGUGAU UUUUGGAU 1440 AUAUCCAA CUGAUGAG X 2664 CACCUUAUU 3803 20 CGAA AUAAGGUG UUGGAUAU 1441 AAUAUCCA CUGAUGAG X 2665 ACCUUAUUU 3804 CGAA AAUAAGGU UGGAUAUU 1442 GAAUAUCC CUGAUGAG X 2666 CCUUAUUUU 3805 CGAA AAAUAAGG GGAUAUUC 25 1447 CAAUUGAA CUGAUGAG X 2667 UUUUGGAUA 3806 CGAA AUCCAAAA UUCAAUUG 1449 AGCAAUUG CUGAUGAG X 2668 UUGGAUAUU 3807 CGAA AUAUCCAA CAAUUGCU 1450 CAGCAAUU CUGAUGAG X 2669 UGGAUAUUC 3808 30 CGAA AAUAUCCA AAUUGCUG 1454 UUUCCAGC CUGAUGAG X 2670 UAUUCAAUU 3809 CGAA AUUGAAUA GCUGGAAA 1472 UUUCGAUC CUGAUGAG X 2671 AUGGACCUU 3810 CGAA AGGUCCAU GAUCGAAA WO 99/50403 PCT/US99/06507 155 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1476 GGAAUUUC CUGAUGAG X 2672 ACCUUGAUC 3811 CGAA AUCAAGGU GAAAUUCC 5 1482 AGGGUAGG CUGAUGAG X 2673 AUCGAAAUU 3812 CGAA AUUUCGAU CCUACCCU 1483 CAGGGUAG CUGAUGAG X 2674 UCGAAAUUC 3813 CGAA AAUUUCGA CUACCCUG 1486 CAUCAGGG CUGAUGAG X 2675 AAAUUCCUA 3814 10 CGAA AGGAAUUU CCCUGAUG 1496 CCAACAGC CUGAUGAG X 2676 CCUGAUGUU 3815 CGAA ACAUCAGG GCUGUUGG 1502 AGGGAACC CUGAUGAG X 2677 GUUGCUGUU 3816 CGAA ACAGCAAC GGUUCCCU 15 1506 UGAGAGGG CUGAUGAG X 2678 CUGUUGGUU 3817 CGAA ACCAACAG CCCUCUCA 1507 CUGAGAGG CUGAUGAG X 2679 UGUUGGUUC 3818 CGAA AACCAACA CCUCUCAG 1511 GAAUCUGA CUGAUGAG X 2680 GGUUCCCUC 3819 20 CGAA AGGGAACC UCAGAUUC 1513 CUGAAUCU CUGAUGAG X 2681 UUCCCUCUC 3820 CGAA AGAGGGAA AGAUUCAG 1518 AGUUACUG CUGAUGAG X 2682 UCUCAGAUU 3821 CGAA AUCUGAGA CAGUAACU 25 1519 UAGUUACU CUGAUGAG X 2683 CUCAGAUUC 3822 CGAA AAUCUGAG AGUAACUA 1523 AAAAUAGU CUGAUGAG X 2684 GAUUCAGUA 3823 CGAA ACUGAAUC ACUAUUUU 1527 UCUGAAAA CUGAUGAG X 2685 CAGUAACUA 3824 30 CGAA AGUUACUG UUUUCAGA 1529 GAUCUGAA CUGAUGAG X 2686 GUAACUAUU 3825 CGAA AUAGUUAC UUCAGAUC 1530 GGAUCUGA CUGAUGAG X 2687 UAACUAUUU 3826 CGAA AAUAGUUA UCAGAUCC WO 99/50403 PCT/US99/06507 156 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1531 GGGAUCUG CUGAUGAG X 2688 AACUAUUUU 3827 CGAA AAAUAGUU CAGAUCCC 5 1532 CGGGAUCU CUGAUGAG X 2689 ACUAUUUUC 3828 CGAA AAAAUAGU AGAUCCCG 1537 CAGGCCGG CUGAUGAG X 2690 UUUCAGAUC 3829 CGAA AUCUGAAA CCGGCCUG 1550 UGAAUAUU CUGAUGAG X 2691 CCUGUGAUU 3830 10 CGAA AUCACAGG AAUAUUCA 1551 CUGAAUAU CUGAUGAG X 2692 CUGUGAUUA 3831 CGAA AAUCACAG AUAUUCAG 1554 UUUCUGAA CUGAUGAG X 2693 UGAUUAAUA 3832 CGAA AUUAAUCA UUCAGAAA 15 1556 GUUUUCUG CUGAUGAG X 2694 AUUAAUAUU 3833 CGAA AUAUUAAU CAGAAAAC 1557 GGUUUUCU CUGAUGAG X 2695 UUAAUAUUC 3834 CGAA AAUAUUAA AGAAAACC 1568 GUUACUGU CUGAUGAG X 2696 AAAACCAUC 3835 20 CGAA AUGGUUUU ACAGUAAC 1574 UUAGGAGU CUGAUGAG X 2697 AUCACAGUA 3836 CGAA ACUGUGAU ACUCCUAA 1578 UCUGUUAG CUGAUGAG X 2698 CAGUAACUC 3837 CGAA AGUUACUG CUAACAGA 25 1581 AAUUCUGU CUGAUGAG X 2699 UAACUCCUA 3838 CGAA AGGAGUUA ACAGAAUU 1589 CGGAGGUC CUGAUGAG X 2700 AACAGAAUU 3839 CGAA AUUCUGUU GACCUCCG 1595 UUCUGGCG CUGAUGAG X 2701 AUUGACCUC 3840 30 CGAA AGGUCAAU CGCCAGAA 1623 UAUCCCAC CUGAUGAG X 2702 GGGCGCCUA 3841 CGAA AGGCGCCC GUGGGAUA 1631 UGGAGGCA CUGAUGAG X 2703 AGUGGGAUA 3842 CGAA AUCCCACU UGCCUCCA WO 99/50403 PCTIUS99/06507 157 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1637 UUAACCUG CUGAUGAG X 2704 AUAUGCCUC 3843 CGAA AGGCAUAU CAGGUUAA 5 1643 CAGGAUUU CUGAUGAG X 2705 CUCCAGGUU 3844 CGAA ACCUGGAG AAAUCCUG 1644 ACAGGAUU CUGAUGAG X 2706 UCCAGGUUA 3845 CGAA AACCUGGA AAUCCUGU 1648 CAAAACAG CUGAUGAG X 2707 GGUUAAAUC 3846 10 CGAA AUUUAACC CUGUUUUG 1653 AUAUUCAA CUGAUGAG X 2708 AAUCCUGUU 3847 CGAA ACAGGAUU UUGAAUAU 1654 UAUAUUCA CUGAUGAG X 2709 AUCCUGUUU 3848 CGAA AACAGGAU UGAAUAUA 15 1655 GUAUAUUC CUGAUGAG X 2710 UCCUGUUUU 3849 CGAA AAACAGGA GAAUAUAC 1660 UAGCAGUA CUGAUGAG X 2711 UUUUGAAUA 3850 CGAA AUUCAAAA UACUGCUA 1662 GUUAGCAG CUGAUGAG X 2712 UUGAAUAUA 3851 20 CGAA AUAUUCAA CUGCUAAC 1668 AGCGGGGU CUGAUGAG X 2713 AUACUGCUA 3852 CGAA AGCAGUAU ACCCCGCU 1680 AGGAUUAU CUGAUGAG X 2714 CCGCUGGUU 3853 CGAA ACCAGCGG AUAAUCCU 25 1681 AAGGAUUA CUGAUGAG X 2715 CGCUGGUUA 3854 CGAA AACCAGCG UAAUCCUU 1683 UGAAGGAU CUGAUGAG X 2716 CUGGUUAUA 3855 CGAA AUAACCAG AUCCUUCA 1686 UAUUGAAG CUGAUGAG X 2717 GUUAUAAUC 3856 30 CGAA AUUAUAAC CUUCAAUA 1689 UGAUAUUG CUGAUGAG X 2718 AUAAUCCUU 3857 CGAA AGGAUUAU CAAUAUCA 1690 UUGAUAUU CUGAUGAG X 2719 UAAUCCUUC 3858 CGAA AAGGAUUA AAUAUCAA WO 99/50403 PCT/US99/06507 158 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1694 ACAAUUGA CUGAUGAG X 2720 CCUUCAAUA 3859 CGAA AUUGAAGG UCAAUUGU 5 1696 CCACAAUU CUGAUGAG X 2721 UUCAAUAUC 3860 CGAA AUAUUGAA AAUUGUGG 1700 GUGCCCAC CUGAUGAG X 2722 AUAUCAAUU 3861 CGAA AUUGAUAU GUGGGCAC 1712 UCAGCUUC CUGAUGAG X 2723 GGCACACUU 3862 10 CGAA AGUGUGCC GAAGCUGA 1738 AUAGCCCA CUGAUGAG X 2724 AAGAAAAUC 3863 CGAA AUUUUCUU UGGGCUAU 1745 CUUGAGGA CUGAUGAG X 2725 UCUGGGCUA 3864 CGAA AGCCCAGA UCCUCAAG 15 1747 CUCUUGAG CUGAUGAG X 2726 UGGGCUAUC 3865 CGAA AUAGCCCA CUCAAGAG 1750 GAACUCUU CUGAUGAG X 2727 GCUAUCCUC 3866 CGAA AGGAUAGC AAGAGUUC 1757 CGAAACUG CUGAUGAG X 2728 UCAAGAGUU 3867 20 CGAA ACUCUUGA CAGUUUCG 1758 UCGAAACU CUGAUGAG X 2729 CAAGAGUUC 3868 CGAA AACUCUUG AGUUUCGA 1762 GGUUUCGA CUGAUGAG X 2730 AGUUCAGUU 3869 CGAA ACUGAACU UCGAAACC 25 1763 UGGUUUCG CUGAUGAG X 2731 GUUCAGUUU 3870 CGAA AACUGAAC CGAAACCA 1764 UUGGUUUC CUGAUGAG X 2732 UUCAGUUUC 3871 CGAA AAACUGAA GAAACCAA 1776 GGGCUCAG CUGAUGAG X 2733 ACCAAGGUU 3872 30 CGAA ACCUUGGU CUGAGCCC 1777 UGGGCUCA CUGAUGAG X 2734 CCAAGGUUC 3873 CGAA AACCUUGG UGAGCCCA 1789 CUUGAGUA CUGAUGAG X 2735 GCCCAAAUA 3874 CGAA AUUUGGGC UACUCAAG WO 99/50403 PCT/US99/06507 159 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1791 UUCUUGAG CUGAUGAG X 2736 CCAAAUAUA 3875 CGAA AUAUUUGG CUCAAGAA 5 1794 UAGUUCUU CUGAUGAG X 2737 AAUAUACUC 3876 CGAA AGUAUAUU AAGAACUA 1802 UUCAGAGU CUGAUGAG X 2738 CAAGAACUA 3877 CGAA AGUUCUUG ACUCUGAA 1806 CCUCUUCA CUGAUGAG X 2739 AACUAACUC 3878 10 CGAA AGUUAGUU UGAAGAGG 1853 UUAUCCUG CUGAUGAG X 2740 CUGUGGCUA 3879 CGAA AGCCACAG CAGGAUAA 1860 UCUGAUAU CUGAUGAG X 2741 UACAGGAUA 3880 CGAA AUCCUGUA AUAUCAGA 15 1863 AUCUCUGA CUGAUGAG X 2742 AGGAUAAUA 3881 CGAA AUUAUCCU UCAGAGAU 1865 UUAUCUCU CUGAUGAG X 2743 GAUAAUAUC 3882 CGAA AUAUUAUC AGAGAUAA 1872 ACGCAGUU CUGAUGAG X 2744 UCAGAGAUA 3883 20 CGAA AUCUCUGA AACUGCGU 1881 GGGAAUGG CUGAUGAG X 2745 AACUGCGUC 3884 CGAA ACGCAGUU CCAUUCCC 1886 GUUAUGGG CUGAUGAG X 2746 CGUCCCAUU 3885 CGAA AUGGGACG CCCAUAAC 25 1887 AGUUAUGG CUGAUGAG X 2747 GUCCCAUUC 3886 CGAA AAUGGGAC CCAUAACU 1892 GAGGCAGU CUGAUGAG X 2748 AUUCCCAUA 3887 CGAA AUGGGAAU ACUGCCUC 1900 UCUCCACU CUGAUGAG X 2749 AACUGCCUC 3888 30 CGAA AGGCAGUU AGUGGAGA 1910 GGCUCUUG CUGAUGAG X 2750 GUGGAGAUC 3889 CGAA AUCUCCAC CAAGAGCC 1924 GCCUACGA CUGAUGAG X 2751 GCCAAGCUC 3890 CGAA AGCUUGGC UCGUAGGC WO 99/50403 PCTIUS99/06507 160 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1926 UCGCCUAC CUGAUGAG X 2752 CAAGCUCUC 3891 CGAA AGAGCUUG GUAGGCGA 5 1929 CACUCGCC CUGAUGAG X 2753 GCUCUCGUA 3892 CGAA ACGAGAGC GGCGAGUG 1941 UGGAAGUG CUGAUGAG X 2754 GAGUGAAUU 3893 CGAA AUUCACUC CACUUCCA 1942 CUGGAAGU CUGAUGAG X 2755 AGUGAAUUC 3894 10 CGAA AAUUCACU ACUUCCAG 1946 ACUUCUGG CUGAUGAG X 2756 AAUUCACUU 3895 CGAA AGUGAAUU CCAGAAGU 1947 AACUUCUG CUGAUGAG X 2757 AUUCACUUC 3896 CGAA AAGUGAAU CAGAAGUU 15 1955 AUUGGAAG CUGAUGAG X 2758 CCAGAAGUU 3897 CGAA ACUUCUGG CUUCCAAU 1956 AAUUGGAA CUGAUGAG X 2759 CAGAAGUUC 3898 CGAA AACUUCUG UUCCAAUU 1958 AGAAUUGG CUGAUGAG X 2760 GAAGUUCUU 3899 20 CGAA AGAACUUC CCAAUUCU 1959 CAGAAUUG CUGAUGAG X 2761 AAGUUCUUC 3900 CGAA AAGAACUU CAAUUCUG 1964 GAAUUCAG CUGAUGAG X 2762 CUUCCAAUU 3901 CGAA AUUGGAAG CUGAAUUC 25 1965 UGAAUUCA CUGAUGAG X 2763 UUCCAAUUC 3902 CGAA AAUUGGAA UGAAUUCA 1971 UUCAUCUG CUGAUGAG X 2764 UUCUGAAUU 3903 CGAA AUUCAGAA CAGAUGAA 1972 GUUCAUCU CUGAUGAG X 2765 UCUGAAUUC 3904 30 CGAA AAUUCAGA AGAUGAAC 1992 AUCAAUAU CUGAUGAG X 2766 AGACAGCUC 3905 CGAA AGCUGUCU AUAUUGAU 1995 AACAUCAA CUGAUGAG X 2767 CAGCUCAUA 3906 CGAA AUGAGCUG UUGAUGUU WO 99/50403 PCT/US99/06507 161 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 1997 UGAACAUC CUGAUGAG X 2768 GCUCAUAUU 3907 CGAA AUAUGAGC GAUGUUCA 5 2003 AAGAAGUG CUGAUGAG X 2769 AUUGAUGUU 3908 CGAA ACAUCAAU CACUUCUU 2004 UAAGAAGU CUGAUGAG X 2770 UUGAUGUUC 3909 CGAA AACAUCAA ACUUCUUA 2008 CUUUUAAG CUGAUGAG X 2771 UGUUCACUU 3910 10 CGAA AGUGAACA CUUAAAAG 2009 UCUUUUAA CUGAUGAG X 2772 GUUCACUUC 3911 CGAA AAGUGAAC UUAAAAGA 2011 CCUCUUUU CUGAUGAG X 2773 UCACUUCUU 3912 CGAA AGAAGUGA AAAAGAGG 15 2012 CCCUCUUU CUGAUGAG X 2774 CACUUCUUA 3913 CGAA AAGAAGUG AAAGAGGG 2039 CUGUUACA CUGAUGAG X 2775 GACAAUGUA 3914 CGAA ACAUUGUC UGUAACAG 2043 GUUGCUGU CUGAUGAG X 2776 AUGUAUGUA 3915 20 CGAA ACAUACAU ACAGCAAC 2054 UCUAGUUU CUGAUGAG X 2777 AGCAACCUU 3916 CGAA AGGUUGCU AAACUAGA 2055 UUCUAGUU CUGAUGAG X 2778 GCAACCUUA 3917 CGAA AAGGUUGC AACUAGAA 25 2060 UUAUAUUC CUGAUGAG X 2779 CUUAAACUA 3918 CGAA AGUUUAAG GAAUAUAA 2065 AAAAUUUA CUGAUGAG X 2780 ACUAGAAUA 3919 CGAA AUUCUAGU UAAAUUUU 2067 GCAAAAUU CUGAUGAG X 2781 UAGAAUAUA 3920 30 CGAA AUAUUCUA AAUUUUGC 2071 GGGUGCAA CUGAUGAG X 2782 AUAUAAAUU 3921 CGAA AUUUAUAU UUGCACCC 2072 CGGGUGCA CUGAUGAG X 2783 UAUAAAUUU 3922 CGAA AAUUUAUA UGCACCCG WO 99/50403 PCT/US99/06507 162 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2073 UCGGGUGC CUGAUGAG X 2784 AUAAAUUUU 3923 CGAA AAAUUUAU GCACCCGA 5 2091 UUUGUCUU CUGAUGAG X 2785 AAGGAAAUC 3924 CGAA AUUUCCUU AAGACAAA 2101 AAUAAGAA CUGAUGAG X 2786 AGACAAAUU 3925 CGAA AUUUGUCU UUCUUAUU 2102 AAAUAAGA CUGAUGAG X 2787 GACAAAUUU 3926 10 CGAA AAUUUGUC UCUUAUUU 2103 UAAAUAAG CUGAUGAG X 2788 ACAAAUUUU 3927 CGAA AAAUUUGU CUUAUUUA 2104 GUAAAUAA CUGAUGAG X 2789 CAAAUUUUC 3928 CGAA AAAAUUUG UUAUUUAC 15 2106 UGGUAAAU CUGAUGAG X 2790 AAUUUUCUU 3929 CGAA AGAAAAUU AUUUACCA 2107 UUGGUAAA CUGAUGAG X 2791 AUUUUCUUA 3930 CGAA AAGAAAAU UUUACCAA 2109 AAUUGGUA CUGAUGAG X 2792 UUUCUUAUU 3931 20 CGAA AUAAGAAA UACCAAUU 2110 GAAUUGGU CUGAUGAG X 2793 UUCUUAUUU 3932 CGAA AAUAAGAA ACCAAUUC 2111 UGAAUUGG CUGAUGAG X 2794 UCUUAUUUA 3933 CGAA AAAUAAGA CCAAUUCA 25 2117 CCUUUUUG CUGAUGAG X 2795 UUACCAAUU 3934 CGAA AUUGGUAA CAAAAAGG 2118 ACCUUUUU CUGAUGAG X 2796 UACCAAUUC 3935 CGAA AAUUGGUA AAAAAGGU 2129 AGUUCUGG CUGAUGAG X 2797 AAAGGUGUA 3936 30 CGAA ACACCUUU CCAGAACU 2138 UUUAGAAC CUGAUGAG X 2798 CCAGAACUA 3937 CGAA AGUUCUGG GUUCUAAA 2141 UCUUUUAG CUGAUGAG X 2799 GAACUAGUU 3938 CGAA ACUAGUUC CUAAAAGA WO 99/50403 PCT/US99/06507 163 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2142 AUCUUUUA CUGAUGAG X 2800 AACUAGUUC 3939 CGAA AACUAGUU UAAAAGAU 5 2144 UGAUCUUU CUGAUGAG X 2801 CUAGUUCUA 3940 CGAA AGAACUAG AAAGAUCA 2151 AUCCUUCU CUGAUGAG X 2802 UAAAAGAUC 3941 CGAA AUCUUUUA AGAAGGAU 2160 UAAAGCAA CUGAUGAG X 2803 AGAAGGAUA 3942 10 CGAA AUCCUUCU UUGCUUUA 2162 UCUAAAGC CUGAUGAG X 2804 AAGGAUAUU 3943 CGAA AUAUCCUU GCUUUAGA 2166 UAUUUCUA CUGAUGAG X 2805 AUAUUGCUU 3944 CGAA AGCAAUAU UAGAAAUA 15 2167 UUAUUUCU CUGAUGAG X 2806 UAUUGCUUU 3945 CGAA AAGCAAUA AGAAAUAA 2168 GUUAUUUC CUGAUGAG X 2807 AUUGCUUUA 3946 CGAA AAAGCAAU GAAAUAAC 2174 GUCACUGU CUGAUGAG X 2808 UUAGAAAUA 3947 20 CGAA AUUUCUAA ACAGUGAC 2193 UGGGUUGG CUGAUGAG X 2809 ACAGCCCUU 3948 CGAA AGGGCUGU CCAACCCA 2194 UUGGGUUG CUGAUGAG X 2810 CAGCCCUUC 3949 CGAA AAGGGCUG CAACCCAA 25 2208 UUUUGUGG CUGAUGAG X 2811 CAAGGAAUC 3950 CGAA AUUCCUUG CCACAAAA 2241 AAUCAGUU CUGAUGAG X 2812 AUGAGGCUA 3951 CGAA AGCCUCAU AACUGAUU 2249 AACGUUGC CUGAUGAG X 2813 AAACUGAUU 3952 30 CGAA AUCAGUUU GCAACGUU 2257 UGUCUGGA CUGAUGAG X 2814 UGCAACGUU 3953 CGAA ACGUUGCA UCCAGACA 2258 GUGUCUGG CUGAUGAG X 2815 GCAACGUUU 3954 CGAA AACGUUGC CCAGACAC WO 99/50403 PCT/US99/06507 164 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2259 AGUGUCUG CUGAUGAG X 2816 CAACGUUUC 3955 CGAA AAACGUUG CAGACACU 5 2268 AUAGGUUA CUGAUGAG X 2817 CAGACACUU 3956 CGAA AGUGUCUG UAACCUAU 2269 AAUAGGUU CUGAUGAG X 2818 AGACACUUU 3957 CGAA AAGUGUCU AACCUAUU 2270 GAAUAGGU CUGAUGAG X 2819 GACACUUUA 3958 10 CGAA AAAGUGUC ACCUAUUC 2275 AUGCAGAA CUGAUGAG X 2820 UUUAACCUA 3959 CGAA AGGUUAAA UUCUGCAU 2277 AUAUGCAG CUGAUGAG X 2821 UAACCUAUU 3960 CGAA AUAGGUUA CUGCAUAU 15 2278 UAUAUGCA CUGAUGAG X 2822 AACCUAUUC 3961 CGAA AAUAGGUU UGCAUAUA 2284 GUUCUCUA CUGAUGAG X 2823 UUCUGCAUA 3962 CGAA AUGCAGAA UAGAGAAC 2286 CAGUUCUC CUGAUGAG X 2824 CUGCAUAUA 3963 20 CGAA AUAUGCAG GAGAACUG 2301 CUCAGGGA CUGAUGAG X 2825 UGAGGGCUU 3964 CGAA AGCCCUCA UCCCUGAG 2302 UCUCAGGG CUGAUGAG X 2826 GAGGGCUUU 3965 CGAA AAGCCCUC CCCUGAGA 25 2303 UUCUCAGG CUGAUGAG X 2827 AGGGCUUUC 3966 CGAA AAAGCCCU CCUGAGAA 2317 CACAACUC CUGAUGAG X 2828 GAAACAGUU 3967 CGAA ACUGUUUC GAGUUGUG 2322 GGCAACAC CUGAUGAG X 2829 AGUUGAGUU 3968 30 CGAA ACUCAACU GUGUUGCC 2327 UGGUUGGC CUGAUGAG X 2830 AGUUGUGUU 3969 CGAA ACACAACU GCCAACCA 2344 CAGCUUGC CUGAUGAG X 2831 GAAUGGCUC 3970 CGAA AGCCAUUC GCAAGCUG WO 99/50403 PCT/US99/06507 165 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2363 GGAUUUCC CUGAUGAG X 2832 UGUGAGCUC 3971 CGAA AGCUCACA GGAAAUCC 5 2370 UUUAAAAG CUGAUGAG X 2833 UCGGAAAUC 3972 CGAA AUUUCCGA CUUUUAAA 2373 UCUUUUAA CUGAUGAG X 2834 GAAAUCCUU 3973 CGAA AGGAUUUC UUAAAAGA 2374 UUCUUUUA CUGAUGAG X 2835 AAAUCCUUU 3974 10 CGAA AAGGAUUU UAAAAGAA 2375 UUUCUUUU CUGAUGAG X 2836 AAUCCUUUU 3975 CGAA AAAGGAUU AAAAGAAA 2376 AUUUCUUU CUGAUGAG X 2837 AUCCUUUUA 3976 CGAA AAAAGGAU AAAGAAAU 15 2385 GACAUUUG CUGAUGAG X 2838 AAAGAAAUU 3977 CGAA AUUUCUUU CAAAUGUC 2386 UGACAUUU CUGAUGAG X 2839 AAGAAAUUC 3978 CGAA AAUUUCUU AAAUGUCA 2393 UAAAAAGU CUGAUGAG X 2840 UCAAAUGUC 3979 20 CGAA ACAUUUGA ACUUUUUA 2397 CAAAUAAA CUGAUGAG X 2841 AUGUCACUU 3980 CGAA AGUGACAU UUUAUUUG 2398 CCAAAUAA CUGAUGAG X 2842 UGUCACUUU 3981 CGAA AAGUGACA UUAUUUGG 25 2399 ACCAAAUA CUGAUGAG X 2843 GUCACUUUU 3982 CGAA AAAGUGAC UAUUUGGU 2400 AACCAAAU CUGAUGAG X 2844 UCACUUUUU 3983 CGAA AAAAGUGA AUUUGGUU 2401 AAACCAAA CUGAUGAG X 2845 CACUUUUUA 3984 30 CGAA AAAAAGUG UUUGGUUU 2403 UAAAACCA CUGAUGAG X 2846 CUUUUUAUU 3985 CGAA AUAAAAAG UGGUUUUA 2404 UUAAAACC CUGAUGAG X 2847 UUUUUAUUU 3986 CGAA AAUAAAAA GGUUUUAA WO 99/50403 PCTIUS99/06507 166 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2408 GUACUUAA CUGAUGAG X 2848 UAUUUGGUU 3987 CGAA ACCAAAUA UUAAGUAC 5 2409 UGUACUUA CUGAUGAG X 2849 AUUUGGUUU 3988 CGAA AACCAAAU UAAGUACA 2410 UUGUACUU CUGAUGAG X 2850 UUUGGUUUU 3989 CGAA AAACCAAA AAGUACAA 2411 GUUGUACU CUGAUGAG X 2851 UUGGUUUUA 3990 10 CGAA AAAACCAA AGUACAAC 2415 UUCAGUUG CUGAUGAG X 2852 UUUUAAGUA 3991 CGAA ACUUAAAA CAACUGAA 2426 UCAAAGGU CUGAUGAG X 2853 ACUGAAGUC 3992 CGAA ACUUCAGU ACCUUUGA 15 2431 GGGUGUCA CUGAUGAG X 2854 AGUCACCUU 3993 CGAA AGGUGACU UGACACCC 2432 GGGGUGUC CUGAUGAG X 2855 GUCACCUUU 3994 CGAA AAGGUGAC GACACCCC 2443 UAUCCAGA CUGAUGAG X 2856 CACCCCAUA 3995 20 CGAA AUGGGGUG UCUGGAUA 2445 AAUAUCCA CUGAUGAG X 2857 CCCCAUAUC 3996 CGAA AUAUGGGG UGGAUAUU 2451 CAGAUUAA CUGAUGAG X 2858 AUCUGGAUA 3997 CGAA AUCCAGAU UUAAUCUG 25 2453 UUCAGAUU CUGAUGAG X 2859 CUGGAUAUU 3998 CGAA AUAUCCAG AAUCUGAA 2454 CUUCAGAU CUGAUGAG X 2860 UGGAUAUUA 3999 CGAA AAUAUCCA AUCUGAAG 2457 UAACUUCA CUGAUGAG X 2861 AUAUUAAUC 4000 30 CGAA AUUAAUAU UGAAGUUA 2464 UUGUUUCU CUGAUGAG X 2862 UCUGAAGUU 4001 CGAA ACUUCAGA AGAAACAA 2465 GUUGUUUC CUGAUGAG X 2863 CUGAAGUUA 4002 CGAA AACUUCAG GAAACAAC WO 99/50403 PCT/US99/06507 167 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2481 AUUAUCUU CUGAUGAG X 2864 CAAGCAAUC 4003 CGAA AUUGCUUG AAGAUAAU 5 2487 AGCCAAAU CUGAUGAG X 2865 AUCAAGAUA 4004 CGAA AUCUUGAU AUUUGGCU 2490 UGGAGCCA CUGAUGAG X 2866 AAGAUAAUU 4005 CGAA AUUAUCUU UGGCUCCA 2491 UUGGAGCC CUGAUGAG X 2867 AGAUAAUUU 4006 10 CGAA AAUUAUCU GGCUCCAA 2496 UGUAAUUG CUGAUGAG X 2868 AUUUGGCUC 4007 CGAA AGCCAAAU CAAUUACA 2501 UUAGCUGU CUGAUGAG X 2869 GCUCCAAUU 4008 CGAA AUUGGAGC ACAGCUAA 15 2502 UUUAGCUG CUGAUGAG X 2870 CUCCAAUUA 4009 CGAA AAUUGGAG CAGCUAAA 2508 UUUUGCUU CUGAUGAG X 2871 UUACAGCUA 4010 CGAA AGCUGUAA AAGCAAAA 2522 AGUUCAAU CUGAUGAG X 2872 AAAGUGGUU 4011 20 CGAA ACCACUUU AUUGAACU 2523 CAGUUCAA CUGAUGAG X 2873 AAGUGGUUA 4012 CGAA AACCACUU UUGAACUG 2525 AGCAGUUC CUGAUGAG X 2874 GUGGUUAUU 4013 CGAA AUAACCAC GAACUGCU 25 2534 ACCGAUAA CUGAUGAG X 2875 GAACUGCUU 4014 CGAA AGCAGUUC UUAUCGGU 2535 GACCGAUA CUGAUGAG X 2876 AACUGCUUU 4015 CGAA AAGCAGUU UAUCGGUC 2536 AGACCGAU CUGAUGAG X 2877 ACUGCUUUU 4016 30 CGAA AAAGCAGU AUCGGUCU 2537 GAGACCGA CUGAUGAG X 2878 CUGCUUUUA 4017 CGAA AAAAGCAG UCGGUCUC 2539 CCGAGACC CUGAUGAG X 2879 GCUUUUAUC 4018 CGAA AUAAAAGC GGUCUCGG WO 99/50403 PCTIUS99/06507 168 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2543 ACUCCCGA CUGAUGAG X 2880 UUAUCGGUC 4019 CGAA ACCGAUAA UCGGGAGU 5 2545 CAACUCCC CUGAUGAG X 2881 AUCGGUCUC 4020 CGAA AGACCGAU GGGAGUUG 2552 GGUUUAGC CUGAUGAG X 2882 UCGGGAGUU 4021 CGAA ACUCCCGA GCUAAACC 2556 GGAAGGUU CUGAUGAG X 2883 GAGUUGCUA 4022 10 CGAA AGCAACUC AACCUUCC 2562 CACCUGGG CUGAUGAG X 2884 CUAAACCUU 4023 CGAA AGGUUUAG CCCAGGUG 2563 ACACCUGG CUGAUGAG X 2885 UAAACCUUC 4024 CGAA AAGGUUUA CCAGGUGU 15 2572 CUCCAAAA CUGAUGAG X 2886 CCAGGUGUA 4025 CGAA ACACCUGG UUUUGGAG 2574 ACCUCCAA CUGAUGAG X 2887 AGGUGUAUU 4026 CGAA AUACACCU UUGGAGGU 2575 UACCUCCA CUGAUGAG X 2888 GGUGUAUUU 4027 20 CGAA AAUACACC UGGAGGUA 2576 GUACCUCC CUGAUGAG X 2889 GUGUAUUUU 4028 CGAA AAAUACAC GGAGGUAC 2583 AACAACUG CUGAUGAG X 2890 UUGGAGGUA 4029 CGAA ACCUCCAA CAGUUGUU 25 2588 UCGCCAAC CUGAUGAG X 2891 GGUACAGUU 4030 CGAA ACUGUACC GUUGGCGA 2591 UGCUCGCC CUGAUGAG X 2892 ACAGUUGUU 4031 CGAA ACAACUGU GGCGAGCA 2604 AGAUUUCA CUGAUGAG X 2893 AGCAAGCUA 4032 30 CGAA AGCUUGCU UGAAAUCU 2611 CAUCUUCA CUGAUGAG X 2894 UAUGAAAUC 4033 CGAA AUUUCAUA UGAAGAUG 2631 CUCUAUUA CUGAUGAG X 2895 UGGGAAGUU 4034 CGAA ACUUCCCA UAAUAGAG WO 99/50403 PCTIUS99/06507 169 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2632 ACUCUAUU CUGAUGAG X 2896 GGGAAGUUU 4035 CGAA AACUUCCC AAUAGAGU 5 2633 UACUCUAU CUGAUGAG X 2897 GGAAGUUUA 4036 CGAA AAACUUCC AUAGAGUA 2636 UCAUACUC CUGAUGAG X 2898 AGUUUAAUA 4037 CGAA AUUAAACU GAGUAUGA 2641 UGAAUUCA CUGAUGAG X 2899 AAUAGAGUA 4038 10 CGAA ACUCUAUU UGAAUUCA 2647 UUACCCUG CUGAUGAG X 2900 GUAUGAAUU 4039 CGAA AUUCAUAC CAGGGUAA 2648 AUUACCCU CUGAUGAG X 2901 UAUGAAUUC 4040 CGAA AAUUCAUA AGGGUAAU 15 2654 AAGUUUAU CUGAUGAG X 2902 UUCAGGGUA 4041 CGAA ACCCUGAA AUAAACUU 2657 CCUAAGUU CUGAUGAG X 2903 AGGGUAAUA 4042 CGAA AUUACCCU AACUUAGG 2662 GUUUACCU CUGAUGAG X 2904 AAUAAACUU 4043 20 CGAA AGUUUAUU AGGUAAAC 2663 GGUUUACC CUGAUGAG X 2905 AUAAACUUA 4044 CGAA AAGUUUAU GGUAAACC 2667 AAGAGGUU CUGAUGAG X 2906 ACUUAGGUA 4045 CGAA ACCUAAGU AACCUCUU 25 2673 GUUUGUAA CUGAUGAG X 2907 GUAAACCUC 4046 CGAA AGGUUUAC UUACAAAC 2675 AGGUUUGU CUGAUGAG X 2908 AAACCUCUU 4047 CGAA AGAGGUUU ACAAACCU 2676 GAGGUUUG CUGAUGAG X 2909 AACCUCUUA 4048 30 CGAA AAGAGGUU CAAACCUC 2684 GCUGUGCC CUGAUGAG X 2910 ACAAACCUC 4049 CGAA AGGUUUGU GGCACAGC 2698 GAAUGUUC CUGAUGAG X 2911 AGCAACCUU 4050 CGAA AGGUUGCU GAACAUUC WO 99/50403 PCT/US99/06507 170 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2705 GGCCACUG CUGAUGAG X 2912 UUGAACAUU 4051 CGAA AUGUUCAA CAGUGGCC 5 2706 UGGCCACU CUGAUGAG X 2913 UGAACAUUC 4052 CGAA AAUGUUCA AGUGGCCA 2723 CCAUUGCU CUGAUGAG X 2914 AAAGAAAUU 4053 CGAA AUUUCUUU AGCAAUGG 2724 CCCAUUGC CUGAUGAG X 2915 AAGAAAUUA 4054 10 CGAA AAUUUCUU GCAAUGGG 2740 AAUAAAGC CUGAUGAG X 2916 GAAAUGGUU 4055 CGAA ACCAUUUC GCUUUAUU 2744 ACCAAAUA CUGAUGAG X 2917 UGGUUGCUU 4056 CGAA AGCAACCA UAUUUGGU 15 2745 CACCAAAU CUGAUGAG X 2918 GGUUGCUUU 4057 CGAA AAGCAACC AUUUGGUG 2746 UCACCAAA CUGAUGAG X 2919 GUUGCUUUA 4058 CGAA AAAGCAAC UUUGGUGA 2748 UUUCACCA CUGAUGAG X 2920 UGCUUUAUU 4059 20 CGAA AUAAAGCA UGGUGAAA 2749 CUUUCACC CUGAUGAG X 2921 GCUUUAUUU 4060 CGAA AAUAAAGC GGUGAAAG 2759 UUGGAUUC CUGAUGAG X 2922 GUGAAAGUA 4061 CGAA ACUUUCAC GAAUCCAA 25 2764 AUCCUUUG CUGAUGAG X 2923 AGUAGAAUC 4062 CGAA AUUCUACU CAAAGGAU 2773 CCUUUUCC CUGAUGAG X 2924 CAAAGGAUU 4063 CGAA AUCCUUUG GGAAAAGG 2783 UCACAAGU CUGAUGAG X 2925 GAAAAGGUA 4064 30 CGAA ACCUUUUC ACUUGUGA 2787 UGGCUCAC CUGAUGAG X 2926 AGGUAACUU 4065 CGAA AGUUACCU GUGAGCCA 2807 AGGGAGUU CUGAUGAG X 2927 AAGGAGAUA 4066 CGAA AUCUCCUU AACUCCCU WO 99/50403 PCTIUS99/06507 171 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2812 GGUUCAGG CUGAUGAG X 2928 GAUAAACUC 4067 CGAA AGUUUAUC CCUGAACC 5 2822 GACUCCGU CUGAUGAG X 2929 CUGAACCUA 4068 CGAA AGGUUCAG ACGGAGUC 2830 AGUUGUGA CUGAUGAG X 2930 AACGGAGUC 4069 CGAA ACUCCGUU UCACAACU 2832 UGAGUUGU CUGAUGAG X 2931 CGGAGUCUC 4070 10 CGAA AGACUCCG ACAACUCA 2839 UCUUUCUU CUGAUGAG X 2932 UCACAACUC 4071 CGAA AGUUGUGA AAGAAAGA 2858 UUUUCAGU CUGAUGAG X 2933 CGGGAAAUU 4072 CGAA AUUUCCCG ACUGAAAA 15 2859 UUUUUCAG CUGAUGAG X 2934 GGGAAAUUA 4073 CGAA AAUUUCCC CUGAAAAA 2873 UUAUCAUC CUGAUGAG X 2935 AAACAGAUA 4074 CGAA AUCUGUUU GAUGAUAA 2880 UUUUCUGU CUGAUGAG X 2936 UAGAUGAUA 4075 20 CGAA AUCAUCUA ACAGAAAA 2890 AUAAAGAA CUGAUGAG X 2937 CAGAAAAUU 4076 CGAA AUUUUCUG UUCUUUAU 2891 AAUAAAGA CUGAUGAG X 2938 AGAAAAUUU 4077 CGAA AAUUUUCU UCUUUAUU 25 2892 AAAUAAAG CUGAUGAG X 2939 GAAAAUUUU 4078 CGAA AAAUUUUC CUUUAUUU 2893 CAAAUAAA CUGAUGAG X 2940 AAAAUUUUC 4079 CGAA AAAAUUUU UUUAUUUG 2895 AGCAAAUA CUGAUGAG X 2941 AAUUUUCUU 4080 30 CGAA AGAAAAUU UAUUUGCU 2896 CAGCAAAU CUGAUGAG X 2942 AUUUUCUUU 4081 CGAA AAGAAAAU AUUUGCUG 2897 UCAGCAAA CUGAUGAG X 2943 UUUUCUUUA 4082 CGAA AAAGAAAA UUUGCUGA WO 99/50403 PCT/US99/06507 172 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 2899 UUUCAGCA CUGAUGAG X 2944 UUCUUUAUU 4083 CGAA AUAAAGAA UGCUGAAA 5 2900 CUUUCAGC CUGAUGAG X 2945 UCUUUAUUU 4084 CGAA AAUAAAGA GCUGAAAG 2914 GAGUCUGG CUGAUGAG X 2946 AAGAAAAUA 4085 CGAA AUUUUCUU CCAGACUC 2922 ACAGUUAA CUGAUGAG X 2947 ACCAGACUC 4086 10 CGAA AGUCUGGU UUAACUGU 2924 CUACAGUU CUGAUGAG X 2948 CAGACUCUU 4087 CGAA AGAGUCUG AACUGUAG 2925 GCUACAGU CUGAUGAG X 2949 AGACUCUUA 4088 CGAA AAGAGUCU ACUGUAGC 15 2931 GUUCACGC CUGAUGAG X 2950 UUAACUGUA 4089 CGAA ACAGUUAA GCGUGAAC 2957 GGGCAUCU CUGAUGAG X 2951 GUGAACAUC 4090 CGAA AUGUUCAC AGAUGCCC 2992 AAAUAAGA CUGAUGAG X 2952 CAAGGCGUC 4091 20 CGAA ACGCCUUG UCUUAUUU 2994 CAAAAUAA CUGAUGAG X 2953 AGGCGUCUC 4092 CGAA AGACGCCU UUAUUUUG 2996 CGCAAAAU CUGAUGAG X 2954 GCGUCUCUU 4093 CGAA AGAGACGC AUUUUGCG 25 2997 GCGCAAAA CUGAUGAG X 2955 CGUCUCUUA 4094 CGAA AAGAGACG UUUUGCGC 2999 GAGCGCAA CUGAUGAG X 2956 UCUCUUAUU 4095 CGAA AUAAGAGA UUGCGCUC 3000 CGAGCGCA CUGAUGAG X 2957 CUCUUAUUU 4096 30 CGAA AAUAAGAG UGCGCUCG 3001 UCGAGCGC CUGAUGAG X 2958 UCUUAUUUU 4097 CGAA AAAUAAGA GCGCUCGA 3007 AUAACCUC CUGAUGAG X 2959 UUUGCGCUC 4098 CGAA AGCGCAAA GAGGUUAU WO 99/50403 PCTIUS99/06507 173 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3013 UGUUCCAU CUGAUGAG X 2960 CUCGAGGUU 4099 CGAA ACCUCGAG AUGGAACA 5 3014 CUGUUCCA CUGAUGAG X 2961 UCGAGGUUA 4100 CGAA AACCUCGA UGGAACAG 3028 CCUCUAGA CUGAUGAG X 2962 CAGCACAUU 4101 CGAA AUGUGCUG UCUAGAGG 3029 UCCUCUAG CUGAUGAG X 2963 AGCACAUUU 4102 10 CGAA AAUGUGCU CUAGAGGA 3030 UUCCUCUA CUGAUGAG X 2964 GCACAUUUC 4103 CGAA AAAUGUGC UAGAGGAA 3032 UAUUCCUC CUGAUGAG X 2965 ACAUUUCUA 4104 CGAA AGAAAUGU GAGGAAUA 15 3040 GUUUGGAA CUGAUGAG X 2966 AGAGGAAUA 4105 CGAA AUUCCUCU UUCCAAAC 3042 CAGUUUGG CUGAUGAG X 2967 AGGAAUAUU 4106 CGAA AUAUUCCU CCAAACUG 3043 UCAGUUUG CUGAUGAG X 2968 GGAAUAUUC 4107 20 CGAA AAUAUUCC CAAACUGA 3055 UGUCCAAG CUGAUGAG X 2969 ACUGAACUA 4108 CGAA AGUUCAGU CUUGGACA 3058 GAAUGUCC CUGAUGAG X 2970 GAACUACUU 4109 CGAA AGUAGUUC GGACAUUC 25 3065 CGCAUGAG CUGAUGAG X 2971 UUGGACAUU 4110 CGAA AUGUCCAA CUCAUGCG 3066 UCGCAUGA CUGAUGAG X 2972 UGGACAUUC 4111 CGAA AAUGUCCA UCAUGCGA 3068 GCUCGCAU CUGAUGAG X 2973 GACAUUCUC 4112 30 CGAA AGAAUGUC AUGCGAGC 3079 CAUCAAUG CUGAUGAG X 2974 GCGAGCCUU 4113 CGAA AGGCUCGC CAUUGAUG 3080 ACAUCAAU CUGAUGAG X 2975 CGAGCCUUC 4114 CGAA AAGGCUCG AUUGAUGU WO 99/50403 PCTIUS99/06507 174 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3083 GUCACAUC CUGAUGAG X 2976 GCCUUCAUU 4115 CGAA AUGAAGGC GAUGUGAC 5 3108 CAGCCUGA CUGAUGAG X 2977 CCGAAAAUA 4116 CGAA AUUUUCGG UCAGGCUG 3110 GGCAGCCU CUGAUGAG X 2978 GAAAAUAUC 4117 CGAA AUAUUUUC AGGCUGCC 3132 UCGAACCU CUGAUGAG X 2979 CAGGCACUC 4118 10 CGAA AGUGCCUG AGGUUCGA 3137 GUCACUCG CUGAUGAG X 2980 ACUCAGGUU 4119 CGAA ACCUGAGU CGAGUGAC 3138 AGUCACUC CUGAUGAG X 2981 CUCAGGUUC 4120 CGAA AACCUGAG GAGUGACU 15 3151 UUGAGGGA CUGAUGAG X 2982 GACUGUGUU 4121 CGAA ACACAGUC UCCCUCAA 3152 UUUGAGGG CUGAUGAG X 2983 ACUGUGUUU 4122 CGAA AACACAGU CCCUCAAA 3153 CUUUGAGG CUGAUGAG X 2984 CUGUGUUUC 4123 20 CGAA AAACACAG CCUCAAAG 3157 CAGUCUUU CUGAUGAG X 2985 GUUUCCCUC 4124 CGAA AGGGAAAC AAAGACUG 3167 UACUGAGC CUGAUGAG X 2986 AAGACUGUA 4125 CGAA ACAGUCUU GCUCAGUA 25 3171 CGAAUACU CUGAUGAG X 2987 CUGUAGCUC 4126 CGAA AGCUACAG AGUAUUCG 3175 CUCCCGAA CUGAUGAG X 2988 AGCUCAGUA 4127 CGAA ACUGAGCU UUCGGGAG 3177 UACUCCCG CUGAUGAG X 2989 CUCAGUAUU 4128 30 CGAA AUACUGAG CGGGAGUA 3178 GUACUCCC CUGAUGAG X 2990 UCAGUAUUC 4129 CGAA AAUACUGA GGGAGUAC 3185 CACCAAGG CUGAUGAG X 2991 UCGGGAGUA 4130 CGAA ACUCCCGA CCUUGGUG WO 99/50403 PCT/US99/06507 175 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3189 GAUCCACC CUGAUGAG X 2992 GAGUACCUU 4131 CGAA AGGUACUC GGUGGAUC 5 3197 ACUAGGAU CUGAUGAG X 2993 UGGUGGAUC 4132 CGAA AUCCACCA AUCCUAGU 3200 GCCACUAG CUGAUGAG X 2994 UGGAUCAUC 4133 CGAA AUGAUCCA CUAGUGGC 3203 AUAGCCAC CUGAUGAG X 2995 AUCAUCCUA 4134 10 CGAA AGGAUGAU GUGGCUAU 3210 AGCGAGAA CUGAUGAG X 2996 UAGUGGCUA 4135 CGAA AGCCACUA UUCUCGCU 3212 CCAGCGAG CUGAUGAG X 2997 GUGGCUAUU 4136 CGAA AUAGCCAC CUCGCUGG 15 3213 CCCAGCGA CUGAUGAG X 2998 UGGCUAUUC 4137 CGAA AAUAGCCA UCGCUGGG 3215 AUCCCAGC CUGAUGAG X 2999 GCUAUUCUC 4138 CGAA AGAAUAGC GCUGGGAU 3224 AGCAUCAA CUGAUGAG X 3000 GCUGGGAUC 4139 20 CGAA AUCCCAGC UUGAUGCU 3226 CAAGCAUC CUGAUGAG X 3001 UGGGAUCUU 4140 CGAA AGAUCCCA GAUGCUUG 3233 AAUAAAGC CUGAUGAG X 3002 UUGAUGCUU 4141 CGAA AGCAUCAA GCUUUAUU 25 3237 CACUAAUA CUGAUGAG X 3003 UGCUUGCUU 4142 CGAA AGCAAGCA UAUUAGUG 3238 ACACUAAU CUGAUGAG X 3004 GCUUGCUUU 4143 CGAA AAGCAAGC AUUAGUGU 3239 AACACUAA CUGAUGAG X 3005 CUUGCUUUA 4144 30 CGAA AAAGCAAG UUAGUGUU 3241 UAAACACU CUGAUGAG X 3006 UGCUUUAUU 4145 CGAA AUAAAGCA AGUGUUUA 3242 AUAAACAC CUGAUGAG X 3007 GCUUUAUUA 4146 CGAA AAUAAAGC GUGUUUAU WO 99/50403 PCT/US99/06507 176 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3247 AUAGUAUA CUGAUGAG X 3008 AUUAGUGUU 4147 CGAA ACACUAAU UAUACUAU 5 3248 CAUAGUAU CUGAUGAG X 3009 UUAGUGUUU 4148 CGAA AACACUAA AUACUAUG 3249 CCAUAGUA CUGAUGAG X 3010 UAGUGUUUA 4149 CGAA AAACACUA UACUAUGG 3251 UUCCAUAG CUGAUGAG X 3011 GUGUUUAUA 4150 10 CGAA AUAAACAC CUAUGGAA 3254 CACUUCCA CUGAUGAG X 3012 UUUAUACUA 4151 CGAA AGUAUAAA UGGAAGUG 3267 CUUGAAGA CUGAUGAG X 3013 AGUGUGGUU 4152 CGAA ACCACACU UCUUCAAG 15 3268 UCUUGAAG CUGAUGAG X 3014 GUGUGGUUU 4153 CGAA AACCACAC CUUCAAGA 3269 CUCUUGAA CUGAUGAG X 3015 UGUGGUUUC 4154 CGAA AAACCACA UUCAAGAG 3271 UUCUCUUG CUGAUGAG X 3016 UGGUUUCUU 4155 20 CGAA AGAAACCA CAAGAGAA 3272 UUUCUCUU CUGAUGAG X 3017 GGUUUCUUC 4156 CGAA AAGAAACC AAGAGAAA 3282 AUCUUUCU CUGAUGAG X 3018 AGAGAAAUA 4157 CGAA AUUUCUCU AGAAAGAU 25 3291 AUCAUAAU CUGAUGAG X 3019 AGAAAGAUC 4158 CGAA AUCUUUCU AUUAUGAU 3294 GGCAUCAU CUGAUGAG X 3020 AAGAUCAUU 4159 CGAA AUGAUCUU AUGAUGCC 3295 UGGCAUCA CUGAUGAG X 3021 AGAUCAUUA 4160 30 CGAA AAUGAUCU UGAUGCCA 3307 CCUUGUGA CUGAUGAG X 3022 UGCCACAUA 4161 CGAA AUGUGGCA UCACAAGG 3309 AGCCUUGU CUGAUGAG X 3023 CCACAUAUC 4162 CGAA AUAUGUGG ACAAGGCU WO 99/50403 PCTIUS99/06507 177 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3323 UGAGCAUG CUGAUGAG X 3024 GCUGAGAUC 4163 CGAA AUCUCAGC CAUGCUCA 5 3330 AGAUGGCU CUGAUGAG X 3025 UCCAUGCUC 4164 CGAA AGCAUGGA AGCCAUCU 3337 CUUUAUCA CUGAUGAG X 3026 UCAGCCAUC 4165 CGAA AUGGCUGA UGAUAAAG 3342 CCUCUCUU CUGAUGAG X 3027 CAUCUGAUA 4166 10 CGAA AUCAGAUG AAGAGAGG 3353 UCAGAAGU CUGAUGAG X 3028 GAGAGGCUU 4167 CGAA AGCCUCUC ACUUCUGA 3354 AUCAGAAG CUGAUGAG X 3029 AGAGGCUUA 4168 CGAA AAGCCUCU CUUCUGAU 15 3357 UGCAUCAG CUGAUGAG X 3030 GGCUUACUU 4169 CGAA AGUAAGCC CUGAUGCA 3358 AUGCAUCA CUGAUGAG X 3031 GCUUACUUC 4170 CGAA AAGUAAGC UGAUGCAU 3367 AUCAAUAC CUGAUGAG X 3032 UGAUGCAUA 4171 20 CGAA AUGCAUCA GUAUUGAU 3370 UAGAUCAA CUGAUGAG X 3033 UGCAUAGUA 4172 CGAA ACUAUGCA UUGAUCUA 3372 AGUAGAUC CUGAUGAG X 3034 CAUAGUAUU 4173 CGAA AUACUAUG GAUCUACU 25 3376 CAGAAGUA CUGAUGAG X 3035 GUAUUGAUC 4174 CGAA AUCAAUAC UACUUCUG 3378 UACAGAAG CUGAUGAG X 3036 AUUGAUCUA 4175 CGAA AGAUCAAU CUUCUGUA 3381 AAUUACAG CUGAUGAG X 3037 GAUCUACUU 4176 30 CGAA AGUAGAUC CUGUAAUU 3382 CAAUUACA CUGAUGAG X 3038 AUCUACUUC 4177 CGAA AAGUAGAU UGUAAUUG 3386 CACACAAU CUGAUGAG X 3039 ACUUCUGUA 4178 CGAA ACAGAAGU AUUGUGUG WO 99/50403 PCTIUS99/06507 178 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3389 AUCCACAC CUGAUGAG X 3040 UCUGUAAUU 4179 CGAA AUUACAGA GUGUGGAU 5 3398 GUUUAAAG CUGAUGAG X 3041 GUGUGGAUU 4180 CGAA AUCCACAC CUUUAAAC 3399 CGUUUAAA CUGAUGAG X 3042 UGUGGAUUC 4181 CGAA AAUCCACA UUUAAACG 3401 AGCGUUUA CUGAUGAG X 3043 UGGAUUCUU 4182 10 CGAA AGAAUCCA UAAACGCU 3402 GAGCGUUU CUGAUGAG X 3044 GGAUUCUUU 4183 CGAA AAGAAUCC AAACGCUC 3403 AGAGCGUU CUGAUGAG X 3045 GAUUCUUUA 4184 CGAA AAAGAAUC AACGCUCU 15 3410 CGUACCUA CUGAUGAG X 3046 UAAACGCUC 4185 CGAA AGCGUUUA UAGGUACG 3412 AUCGUACC CUGAUGAG X 3047 AACGCUCUA 4186 CGAA AGAGCGUU GGUACGAU 3416 UGUCAUCG CUGAUGAG X 3048 CUCUAGGUA 4187 20 CGAA ACCUAGAG CGAUGACA 3429 UAUCGGGG CUGAUGAG X 3049 GACAGUGUU 4188 CGAA ACACUGUC CCCCGAUA 3430 GUAUCGGG CUGAUGAG X 3050 ACAGUGUUC 4189 CGAA AACACUGU CCCGAUAC 25 3437 CAGCAUGG CUGAUGAG X 3051 UCCCCGAUA 4190 CGAA AUCGGGGA CCAUGCUG 3447 CGGAUCCU CUGAUGAG X 3052 CAUGCUGUA 4191 CGAA ACAGCAUG AGGAUCCG 3453 UCUUUCCG CUGAUGAG X 3053 GUAAGGAUC 4192 30 CGAA AUCCUUAC CGGAAAGA 3474 UCAUCUUU CUGAUGAG X 3054 CGAGAGAUC 4193 CGAA AUCUCUCG AAAGAUGA 3488 UAUCAAUA CUGAUGAG X 3055 UGAAAAGUA 4194 CGAA ACUUUUCA UAUUGAUA WO 99/50403 PCT/US99/06507 179 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3490 GUUAUCAA CUGAUGAG X 3056 AAAAGUAUA 4195 CGAA AUACUUUU UUGAUAAC 5 3492 AGGUUAUC CUGAUGAG X 3057 AAGUAUAUU 4196 CGAA AUAUACUU GAUAACCU 3496 UUCAAGGU CUGAUGAG X 3058 AUAUUGAUA 4197 CGAA AUCAAUAU ACCUUGAA 3501 UUUUUUUC CUGAUGAG X 3059 GAUAACCUU 4198 10 CGAA AGGUUAUC GAAAAAAA 3519 CACUUUGU CUGAUGAG X 3060 CAGUGGAUC 4199 CGAA AUCCACUG ACAAAGUG 3545 GCUAUGAG CUGAUGAG X 3061 UGAAAGCUA 4200 CGAA AGCUUUCA CUCAUAGC 15 3548 CCCGCUAU CUGAUGAG X 3062 AAGCUACUC 4201 CGAA AGUAGCUU AUAGCGGG 3551 GCCCCCGC CUGAUGAG X 3063 CUACUCAUA 4202 CGAA AUGAGUAG GCGGGGGC 3562 UUUUUUUU CUGAUGAG X 3064 GGGGGCCUA 4203 20 CGAA AGGCCCCC AAAAAAAA 3577 GUACUGUG CUGAUGAG X 3065 AAAAAGCUU 4204 CGAA AGCUUUUU CACAGUAC 3578 GGUACUGU CUGAUGAG X 3066 AAAAGCUUC 4205 CGAA AAGCUUUU ACAGUACC 25 3584 AGUUUGGG CUGAUGAG X 3067 UUCACAGUA 4206 CGAA ACUGUGAA CCCAAACU 3596 GUUGGAAA CUGAUGAG X 3068 AAACUGCUU 4207 CGAA AGCAGUUU UUUCCAAC 3597 AGUUGGAA CUGAUGAG X 3069 AACUGCUUU 4208 30 CGAA AAGCAGUU UUCCAACU 3598 GAGUUGGA CUGAUGAG X 3070 ACUGCUUUU 4209 CGAA AAAGCAGU UCCAACUC 3599 UGAGUUGG CUGAUGAG X 3071 CUGCUUUUU 4210 CGAA AAAAGCAG CCAACUCA WO 99/50403 PCT/US99/06507 180 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3600 CUGAGUUG CUGAUGAG X 3072 UGCUUUUUC 4211 CGAA AAAAAGCA CAACUCAG 5 3606 GAAUUUCU CUGAUGAG X 3073 UUCCAACUC 4212 CGAA AGUUGGAA AGAAAUUC 3613 CCAAAUUG CUGAUGAG X 3074 UCAGAAAUU 4213 CGAA AUUUCUGA CAAUUUGG 3614 UCCAAAUU CUGAUGAG X 3075 CAGAAAUUC 4214 10 CGAA AAUUUCUG AAUUUGGA 3618 UAAAUCCA CUGAUGAG X 3076 AAUUCAAUU 4215 CGAA AUUGAAUU UGGAUUUA 3619 UUAAAUCC CUGAUGAG X 3077 AUUCAAUUU 4216 CGAA AAUUGAAU GGAUUUAA 15 3624 GGCUUUUA CUGAUGAG X 3078 AUUUGGAUU 4217 CGAA AUCCAAAU UAAAAGCC 3625 AGGCUUUU CUGAUGAG X 3079 UUUGGAUUU 4218 CGAA AAUCCAAA AAAAGCCU 3626 CAGGCUUU CUGAUGAG X 3080 UUGGAUUUA 4219 20 CGAA AAAUCCAA AAAGCCUG 3637 CAGGGAUU CUGAUGAG X 3081 AGCCUGCUC 4220 CGAA AGCAGGCU AAUCCCUG 3641 UCCUCAGG CUGAUGAG X 3082 UGCUCAAUC 4221 CGAA AUUGAGCA CCUGAGGA 25 3655 CACUCUGA CUGAUGAG X 3083 GGACUGAUU 4222 CGAA AUCAGUCC UCAGAGUG 3656 UCACUCUG CUGAUGAG X 3084 GACUGAUUU 4223 CGAA AAUCAGUC CAGAGUGA 3657 GUCACUCU CUGAUGAG X 3085 ACUGAUUUC 4224 30 CGAA AAAUCAGU AGAGUGAC 3667 ACUGUGUG CUGAUGAG X 3086 GAGUGACUA 4225 CGAA AGUCACUC CACACAGU 3676 UAGGUUCG CUGAUGAG X 3087 CACACAGUA 4226 CGAA ACUGUGUG CGAACCUA WO 99/50403 PCT/US99/06507 181 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3684 UAAAACUG CUGAUGAG X 3088 ACGAACCUA 4227 CGAA AGGUUCGU CAGUUUUA 3689 ACAGUUAA CUGAUGAG X 3089 CCUACAGUU 4228 CGAA ACUGUAGG UUAACUGU 3690 CACAGUUA CUGAUGAG X 3090 CUACAGUUU 4229 CGAA AACUGUAG UAACUGUG 3691 CCACAGUU CUGAUGAG X 3091 UACAGUUUU 4230 L CGAA AAACUGUA AACUGUGG 3692 UCCACAGU CUGAUGAG X 3092 ACAGUUUUA 4231 CGAA AAAACUGU ACUGUGGA 3702 CGUAACAA CUGAUGAG X 3093 CUGUGGAUA 4232 CGAA AUCCACAG UUGUUACG L5 3704 UACGUAAC CUGAUGAG X 3094 GUGGAUAUU 4233 CGAA AUAUCCAC GUUACGUA 3707 GGCUACGU CUGAUGAG X 3095 GAUAUUGUU 4234 CGAA ACAAUAUC ACGUAGCC 3708 AGGCUACG CUGAUGAG X 3096 AUAUUGUUA 4235 ?0 CGAA AACAAUAU CGUAGCCU 3712 CCUUAGGC CUGAUGAG X 3097 UGUUACGUA 4236 CGAA ACGUAACA GCCUAAGG 3717 AGGAGCCU CUGAUGAG X 3098 CGUAGCCUA 4237 CGAA AGGCUACG AGGCUCCU 3723 CAAAACAG CUGAUGAG X 3099 CUAAGGCUC 4238 CGAA AGCCUUAG CUGUUUUG 3728 CUGUGCAA CUGAUGAG X 3100 GCUCCUGUU 4239 CGAA ACAGGAGC UUGCACAG 3729 GCUGUGCA CUGAUGAG X 3101 CUCCUGUUU 4240 30 CGAA AACAGGAG UGCACAGC 3730 GGCUGUGC CUGAUGAG X 3102 UCCUGUUUU 4241 CGAA AAACAGGA GCACAGCC 3743 CAGUUUUA CUGAUGAG X 3103 AGCCAAAUU 4242 CGAA AUUUGGCU UAAAACUG WO 99/50403 PCTIUS99/06507 182 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3744 ACAGUUUU CUGAUGAG X 3104 GCCAAAUUU 4243 CGAA AAUUUGGC AAAACUGU 5 3745 AACAGUUU CUGAUGAG X 3105 CCAAAUUUA 4244 CGAA AAAUUUGG AAACUGUU 3753 UCCAUUCC CUGAUGAG X 3106 AAAACUGUU 4245 CGAA ACAGUUUU GGAAUGGA 3763 UAAAGAAA CUGAUGAG X 3107 GAAUGGAUU 4246 10 CGAA AUCCAUUC UUUCUUUA 3764 UUAAAGAA CUGAUGAG X 3108 AAUGGAUUU 4247 CGAA AAUCCAUU UUCUUUAA 3765 GUUAAAGA CUGAUGAG X 3109 AUGGAUUUU 4248 CGAA AAAUCCAU UCUUUAAC 15 3766 AGUUAAAG CUGAUGAG X 3110 UGGAUUUUU 4249 CGAA AAAAUCCA CUUUAACU 3767 CAGUUAAA CUGAUGAG X 3111 GGAUUUUUC 4250 CGAA AAAAAUCC UUUAACUG 3769 GGCAGUUA CUGAUGAG X 3112 AUUUUUCUU 4251 20 CGAA AGAAAAAU UAACUGCC 3770 CGGCAGUU CUGAUGAG X 3113 UUUUUCUUU 4252 CGAA AAGAAAAA AACUGCCG 3771 ACGGCAGU CUGAUGAG X 3114 UUUUCUUUA 4253 CGAA AAAGAAAA ACUGCCGU 25 3780 AGUUAAAU CUGAUGAG X 3115 ACUGCCGUA 4254 CGAA ACGGCAGU AUUUAACU 3783 GAAAGUUA CUGAUGAG X 3116 GCCGUAAUU 4255 CGAA AUUACGGC UAACUUUC 3784 AGAAAGUU CUGAUGAG X 3117 CCGUAAUUU 4256 30 CGAA AAUUACGG AACUUUCU 3785 CAGAAAGU CUGAUGAG X 3118 CGUAAUUUA 4257 CGAA AAAUUACG ACUUUCUG 3789 AACCCAGA CUGAUGAG X 3119 AUUUAACUU 4258 CGAA AGUUAAAU UCUGGGUU WO 99/50403 PCTIUS99/06507 183 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3790 CAACCCAG CUGAUGAG X 3120 UUUAACUUU 4259 CGAA AAGUUAAA CUGGGUUG 5 3791 GCAACCCA CUGAUGAG X 3121 UUAACUUUC 4260 CGAA AAAGUUAA UGGGUUGC 3797 ACAAAGGC CUGAUGAG X 3122 UUCUGGGUU 4261 CGAA ACCCAGAA GCCUUUGU 3802 CAAAAACA CUGAUGAG X 3123 GGUUGCCUU 4262 10 CGAA AGGCAACC UGUUUUUG 3803 CCAAAAAC CUGAUGAG X 3124 GUUGCCUUU 4263 CGAA AAGGCAAC GUUUUUGG 3806 ACGCCAAA CUGAUGAG X 3125 GCCUUUGUU 4264 CGAA ACAAAGGC UUUGGCGU 15 3807 CACGCCAA CUGAUGAG X 3126 CCUUUGUUU 4265 CGAA AACAAAGG UUGGCGUG 3808 CCACGCCA CUGAUGAG X 3127 CUUUGUUUU 4266 CGAA AAACAAAG UGGCGUGG 3809 GCCACGCC CUGAUGAG X 3128 UUUGUUUUU 4267 20 CGAA AAAACAAA GGCGUGGC 3823 CAUGAUGU CUGAUGAG X 3129 GGCUGACUU 4268 CGAA AGUCAGCC ACAUCAUG 3824 ACAUGAUG CUGAUGAG X 3130 GCUGACUUA 4269 CGAA AAGUCAGC CAUCAUGU 25 3828 CAACACAU CUGAUGAG X 3131 ACUUACAUC 4270 CGAA AUGUAAGU AUGUGUUG 3835 CCUUCCCC CUGAUGAG X 3132 UCAUGUGUU 4271 CGAA ACACAUGA GGGGAAGG 3855 CUGAGUGC CUGAUGAG X 3133 UGCCCAGUU 4272 30 CGAA ACUGGGCA GCACUCAG 3861 UGUCACCU CUGAUGAG X 3134 GUUGCACUC 4273 CGAA AGUGCAAC AGGUGACA 3871 AUCUGGAG CUGAUGAG X 3135 GGUGACAUC 4274 CGAA AUGUCACC CUCCAGAU WO 99/50403 PCTIUS99/06507 184 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3874 ACUAUCUG CUGAUGAG X 3136 GACAUCCUC 4275 CGAA AGGAUGUC CAGAUAGU 5 3880 AGCUACAC CUGAUGAG X 3137 CUCCAGAUA 4276 CGAA AUCUGGAG GUGUAGCU 3885 UCCUCAGC CUGAUGAG X 3138 GAUAGUGUA 4277 CGAA ACACUAUC GCUGAGGA 3901 GGUGAGUG CUGAUGAG X 3139 AGGCACCUA 4278 10 CGAA AGGUGCCU CACUCACC 3906 GUGCAGGU CUGAUGAG X 3140 CCUACACUC 4279 CGAA AGUGUAGG ACCUGCAC 3916 CACUCUGU CUGAUGAG X 3141 CCUGCACUA 4280 CGAA AGUGCAGG ACAGAGUG 15 3930 GAGGUUAG CUGAUGAG X 3142 GUGGCCGUC 4281 CGAA ACGGCCAC CUAACCUC 3933 CCCGAGGU CUGAUGAG X 3143 GCCGUCCUA 4282 CGAA AGGACGGC ACCUCGGG 3938 GCAGGCCC CUGAUGAG X 3144 CCUAACCUC 4283 20 CGAA AGGUUAGG GGGCCUGC 3958 ACGUGAUG CUGAUGAG X 3145 GCAGACGUC 4284 CGAA ACGUCUGC CAUCACGU 3962 GCUAACGU CUGAUGAG X 3146 ACGUCCAUC 4285 CGAA AUGGACGU ACGUUAGC 25 3967 GGACAGCU CUGAUGAG X 3147 CAUCACGUU 4286 CGAA ACGUGAUG AGCUGUCC 3968 GGGACAGC CUGAUGAG X 3148 AUCACGUUA 4287 CGAA AACGUGAU GCUGUCCC 3974 UGAUGUGG CUGAUGAG X 3149 UUAGCUGUC 4288 30 CGAA ACAGCUAA CCACAUCA 3981 AGUCUUGU CUGAUGAG X 3150 UCCCACAUC 4289 CGAA AUGUGGGA ACAAGACU 3990 CAAUGGCA CUGAUGAG X 3151 ACAAGACUA 4290 CGAA AGUCUUGU UGCCAUUG WO 99/50403 PCT/US99/06507 185 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 3997 ACUACCCC CUGAUGAG X 3152 UAUGCCAUU 4291 CGAA AUGGCAUA GGGGUAGU 5 4003 AACACAAC CUGAUGAG X 3153 AUUGGGGUA 4292 CGAA ACCCCAAU GUUGUGUU 4006 UGAAACAC CUGAUGAG X 3154 GGGGUAGUU 4293 CGAA ACUACCCC GUGUUUCA 4011 UCCGUUGA CUGAUGAG X 3155 AGUUGUGUU 4294 10 CGAA ACACAACU UCAACGGA 4012 UUCCGUUG CUGAUGAG X 3156 GUUGUGUUU 4295 CGAA AACACAAC CAACGGAA 4013 UUUCCGUU CUGAUGAG X 3157 UUGUGUUUC 4296 CGAA AAACACAA AACGGAAA 15 4029 UAGUUUAA CUGAUGAG X 3158 AGUGCUGUC 4297 CGAA ACAGCACU UUAAACUA 4031 UUUAGUUU CUGAUGAG X 3159 UGCUGUCUU 4298 CGAA AGACAGCA AAACUAAA 4032 AUUUAGUU CUGAUGAG X 3160 GCUGUCUUA 4299 20 CGAA AAGACAGC AACUAAAU 4037 UGCACAUU CUGAUGAG X 3161 CUUAAACUA 4300 CGAA AGUUUAAG AAUGUGCA 4048 UCACCUUC CUGAUGAG X 3162 UGUGCAAUA 4301 CGAA AUUGCACA GAAGGUGA 25 4060 AGGAUGGC CUGAUGAG X 3163 GGUGAUGUU 4302 CGAA ACAUCACC GCCAUCCU 4066 GACGGUAG CUGAUGAG X 3164 GUUGCCAUC 4303 CGAA AUGGCAAC CUACCGUC 4069 AAAGACGG CUGAUGAG X 3165 GCCAUCCUA 4304 30 CGAA AGGAUGGC CCGUCUUU 4074 CAGGAAAA CUGAUGAG X 3166 CCUACCGUC 4305 CGAA ACGGUAGG UUUUCCUG 4076 AACAGGAA CUGAUGAG X 3167 UACCGUCUU 4306 CGAA AGACGGUA UUCCUGUU WO 99/50403 PCT/US99/06507 186 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4077 AAACAGGA CUGAUGAG X 3168 ACCGUCUUU 4307 CGAA AAGACGGU UCCUGUUU 5 4078 GAAACAGG CUGAUGAG X 3169 CCGUCUUUU 4308 CGAA AAAGACGG CCUGUUUC 4079 GGAAACAG CUGAUGAG X 3170 CGUCUUUUC 4309 CGAA AAAAGACG CUGUUUCC 4084 AGCUAGGA CUGAUGAG X 3171 UUUCCUGUU 4310 10 CGAA ACAGGAAA UCCUAGCU 4085 CAGCUAGG CUGAUGAG X 3172 UUCCUGUUU 4311 CGAA AACAGGAA CCUAGCUG 4086 ACAGCUAG CUGAUGAG X 3173 UCCUGUUUC 4312 CGAA AAACAGGA CUAGCUGU 15 4089 CACACAGC CUGAUGAG X 3174 UGUUUCCUA 4313 CGAA AGGAAACA GCUGUGUG 4101 UGAGCAGG CUGAUGAG X 3175 GUGUGAAUA 4314 CGAA AUUCACAC CCUGCUCA 4108 UUUGACGU CUGAUGAG X 3176 UACCUGCUC 4315 20 CGAA AGCAGGUA ACGUCAAA 4113 AUGCAUUU CUGAUGAG X 3177 GCUCACGUC 4316 CGAA ACGUGAGC AAAUGCAU 4122 GAAACUUG CUGAUGAG X 3178 AAAUGCAUA 4317 CGAA AUGCAUUU CAAGUUUC 4128 GAGAAUGA CUGAUGAG X 3179 AUACAAGUU 4318 CGAA ACUUGUAU UCAUUCUC 4129 GGAGAAUG CUGAUGAG X 3180 UACAAGUUU 4319 CGAA AACUUGUA CAUUCUCC 4130 GGGAGAAU CUGAUGAG X 3181 ACAAGUUUC 4320 30 CGAA AAACUUGU AUUCUCCC 4133 AAAGGGAG CUGAUGAG X 3182 AGUUUCAUU 4321 CGAA AUGAAACU CUCCCUUU 4134 GAAAGGGA CUGAUGAG X 3183 GUUUCAUUC 4322 CGAA AAUGAAAC UCCCUUUC WO 99/50403 PCTIUS99/06507 187 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4136 GUGAAAGG CUGAUGAG X 3184 UUCAUUCUC 4323 CGAA AGAAUGAA CCUUUCAC 5 4140 UUUAGUGA CUGAUGAG X 3185 UUCUCCCUU 4324 CGAA AGGGAGAA UCACUAAA 4141 UUUUAGUG CUGAUGAG X 3186 UCUCCCUUU 4325 CGAA AAGGGAGA CACUAAAA 4142 UUUUUAGU CUGAUGAG X 3187 CUCCCUUUC 4326 10 CGAA AAAGGGAG ACUAAAAA 4146 UGUGUUUU CUGAUGAG X 3188 CUUUCACUA 4327 CGAA AGUGAAAG AAAACACA 4170 UAGCAUUC CUGAUGAG X 3189 AACAGACUU 4328 CGAA AGUCUGUU GAAUGCUA 15 4178 AGUAUAAC CUGAUGAG X 3190 UGAAUGCUA 4329 CGAA AGCAUUCA GUUAUACU 4181 AUAAGUAU CUGAUGAG X 3191 AUGCUAGUU 4330 CGAA ACUAGCAU AUACUUAU 4182 AAUAAGUA CUGAUGAG X 3192 UGCUAGUUA 4331 20 CGAA AACUAGCA UACUUAUU 4184 CAAAUAAG CUGAUGAG X 3193 CUAGUUAUA 4332 CGAA AUAACUAG CUUAUUUG 4187 AUACAAAU CUGAUGAG X 3194 GUUAUACUU 4333 CGAA AGUAUAAC AUUUGUAU 25 4188 UAUACAAA CUGAUGAG X 3195 UUAUACUUA 4334 CGAA AAGUAUAA UUUGUAUA 4190 CAUAUACA CUGAUGAG X 3196 AUACUUAUU 4335 CGAA AUAAGUAU UGUAUAUG 4191 CCAUAUAC CUGAUGAG X 3197 UACUUAUUU 4336 30 CGAA AAUAAGUA GUAUAUGG 4194 AUACCAUA CUGAUGAG X 3198 UUAUUUGUA 4337 CGAA ACAAAUAA UAUGGUAU 4196 AAAUACCA CUGAUGAG X 3199 AUUUGUAUA 4338 CGAA AUACAAAU UGGUAUUU WO 99/50403 PCTIUS99/06507 188 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4201 AAAAUAAA CUGAUGAG X 3200 UAUAUGGUA 4339 CGAA ACCAUAUA UUUAUUUU 5 4203 AAAAAAUA CUGAUGAG X 3201 UAUGGUAUU 4340 CGAA AUACCAUA UAUUUUUU 4204 GAAAAAAU CUGAUGAG X 3202 AUGGUAUUU 4341 CGAA AAUACCAU AUUUUUUC 4205 AGAAAAAA CUGAUGAG X 3203 UGGUAUUUA 4342 10 CGAA AAAUACCA UUUUUUCU 4207 AAAGAAAA CUGAUGAG X 3204 GUAUUUAUU 4343 CGAA AUAAAUAC UUUUCUUU 4208 AAAAGAAA CUGAUGAG X 3205 UAUUUAUUU 4344 CGAA AAUAAAUA UUUCUUUU 15 4209 GAAAAGAA CUGAUGAG X 3206 AUUUAUUUU 4345 CGAA AAAUAAAU UUCUUUUC 4210 AGAAAAGA CUGAUGAG X 3207 UUUAUUUUU 4346 CGAA AAAAUAAA UCUUUUCU 4211 AAGAAAAG CUGAUGAG X 3208 UUAUUUUUU 4347 20 CGAA AAAAAUAA CUUUUCUU 4212 AAAGAAAA CUGAUGAG X 3209 UAUUUUUUC 4348 CGAA AAAAAAUA UUUUCUUU 4214 GUAAAGAA CUGAUGAG X 3210 UUUUUUCUU 4349 CGAA AGAAAAAA UUCUUUAC 25 4215 UGUAAAGA CUGAUGAG X 3211 UUUUUCUUU 4350 CGAA AAGAAAAA UCUUUACA 4216 UUGUAAAG CUGAUGAG X 3212 UUUUCUUUU 4351 CGAA AAAGAAAA CUUUACAA 4217 UUUGUAAA CUGAUGAG X 3213 UUUCUUUUC 4352 30 CGAA AAAAGAAA UUUACAAA 4219 GGUUUGUA CUGAUGAG X 3214 UCUUUUCUU 4353 CGAA AGAAAAGA UACAAACC 4220 UGGUUUGU CUGAUGAG X 3215 CUUUUCUUU 4354 CGAA AAGAAAAG ACAAACCA WO 99/50403 PCT/US99/06507 189 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4221 AUGGUUUG CUGAUGAG X 3216 UUUUCUUUA 4355 CGAA AAAGAAAA CAAACCAU 5 4230 AAUAACAA CUGAUGAG X 3217 CAAACCAUU 4356 CGAA AUGGUUUG UUGUUAUU 4231 CAAUAACA CUGAUGAG X 3218 AAACCAUUU 4357 CGAA AAUGGUUU UGUUAUUG 4232 UCAAUAAC CUGAUGAG X 3219 AACCAUUUU 4358 10 CGAA AAAUGGUU GUUAUUGA 4235 UAGUCAAU CUGAUGAG X 3220 CAUUUUGUU 4359 CGAA ACAAAAUG AUUGACUA 4236 UUAGUCAA CUGAUGAG X 3221 AUUUUGUUA 4360 CGAA AACAAAAU UUGACUAA 15 4238 UGUUAGUC CUGAUGAG X 3222 UUUGUUAUU 4361 CGAA AUAACAAA GACUAACA 4243 UGGCCUGU CUGAUGAG X 3223 UAUUGACUA 4362 CGAA AGUCAAUA ACAGGCCA 4258 AAACUGGA CUGAUGAG X 3224 CAAAGAGUC 4363 20 CGAA ACUCUUUG UCCAGUUU 4260 GUAAACUG CUGAUGAG X 3225 AAGAGUCUC 4364 CGAA AGACUCUU CAGUUUAC 4265 GAAGGGUA CUGAUGAG X 3226 UCUCCAGUU 4365 CGAA ACUGGAGA UACCCUUC 25 4266 UGAAGGGU CUGAUGAG X 3227 CUCCAGUUU 4366 CGAA AACUGGAG ACCCUUCA 4267 CUGAAGGG CUGAUGAG X 3228 UCCAGUUUA 4367 CGAA AAACUGGA CCCUUCAG 4272 CCAACCUG CUGAUGAG X 3229 UUUACCCUU 4368 30 CGAA AGGGUAAA CAGGUUGG 4273 ACCAACCU CUGAUGAG X 3230 UUACCCUUC 4369 CGAA AAGGGUAA AGGUUGGU 4278 AUUAAACC CUGAUGAG X 3231 CUUCAGGUU 4370 CGAA ACCUGAAG GGUUUAAU WO 99/50403 PCTIUS99/06507 190 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4282 AUUGAUUA CUGAUGAG X 3232 AGGUUGGUU 4371 CGAA ACCAACCU UAAUCAAU 5 4283 GAUUGAUU CUGAUGAG X 3233 GGUUGGUUU 4372 CGAA AACCAACC AAUCAAUC 4284 UGAUUGAU CUGAUGAG X 3234 GUUGGUUUA 4373 CGAA AAACCAAC AUCAAUCA 4287 UUCUGAUU CUGAUGAG X 3235 GGUUUAAUC 4374 10 CGAA AUUAAACC AAUCAGAA 4291 CUAAUUCU CUGAUGAG X 3236 UAAUCAAUC 4375 CGAA AUUGAUUA AGAAUUAG 4297 CUAAUUCU CUGAUGAG X 3237 AUCAGAAUU 4376 CGAA AUUCUGAU AGAAUUAG 15 4298 UCUAAUUC CUGAUGAG X 3238 UCAGAAUUA 4377 CGAA AAUUCUGA GAAUUAGA 4303 CAUGCUCU CUGAUGAG X 3239 AUUAGAAUU 4378 CGAA AUUCUAAU AGAGCAUG 4304 CCAUGCUC CUGAUGAG X 3240 UUAGAAUUA 4379 20 CGAA AAUUCUAA GAGCAUGG 4319 AUAGUGAU CUGAUGAG X 3241 GGGAGGGUC 4380 CGAA ACCCUCCC AUCACUAU 4322 GUCAUAGU CUGAUGAG X 3242 AGGGUCAUC 4381 CGAA AUGACCCU ACUAUGAC 25 4326 UUAGGUCA CUGAUGAG X 3243 UCAUCACUA 4382 CGAA AGUGAUGA UGACCUAA 4333 AAAUAAUU CUGAUGAG X 3244 UAUGACCUA 4383 CGAA AGGUCAUA AAUUAUUU 4337 CAGUAAAU CUGAUGAG X 3245 ACCUAAAUU 4384 30 CGAA AUUUAGGU AUUUACUG 4338 GCAGUAAA CUGAUGAG X 3246 CCUAAAUUA 4385 CGAA AAUUUAGG UUUACUGC 4340 UUGCAGUA CUGAUGAG X 3247 UAAAUUAUU 4386 CGAA AUAAUUUA UACUGCAA WO 99/50403 PCT/US99/06507 191 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4341 UUUGCAGU CUGAUGAG X 3248 AAAUUAUUU 4387 CGAA AAUAAUUU ACUGCAAA 5 4342 UUUUGCAG CUGAUGAG X 3249 AAUUAUUUA 4388 CGAA AAAUAAUU CUGCAAAA 4358 UUUAUAAA CUGAUGAG X 3250 AAGAAAAUC 4389 CGAA AUUUUCUU UUUAUAAA 4360 CAUUUAUA CUGAUGAG X 3251 GAAAAUCUU 4390 10 CGAA AGAUUUUC UAUAAAUG 4361 ACAUUUAU CUGAUGAG X 3252 AAAAUCUUU 4391 CGAA AAGAUUUU AUAAAUGU 4362 UACAUUUA CUGAUGAG X 3253 AAAUCUUUA 4392 CGAA AAAGAUUU UAAAUGUA 15 4364 GGUACAUU CUGAUGAG X 3254 AUCUUUAUA 4393 CGAA AUAAAGAU AAUGUACC 4370 CUCUCUGG CUGAUGAG X 3255 AUAAAUGUA 4394 CGAA ACAUUUAU CCAGAGAG 4382 AUUAAAAC CUGAUGAG X 3256 GAGAGAGUU 4395 20 CGAA ACUCUCUC GUUUUAAU 4385 GUUAUUAA CUGAUGAG X 3257 AGAGUUGUU 4396 CGAA ACAACUCU UUAAUAAC 4386 AGUUAUUA CUGAUGAG X 3258 GAGUUGUUU 4397 CGAA AACAACUC UAAUAACU 25 4387 AAGUUAUU CUGAUGAG X 3259 AGUUGUUUU 4398 CGAA AAACAACU AAUAACUU 4388 UAAGUUAU CUGAUGAG X 3260 GUUGUUUUA 4399 CGAA AAAACAAC AUAACUUA 4391 AGAUAAGU CUGAUGAG X 3261 GUUUUAAUA 4400 30 CGAA AUUAAAAC ACUUAUCU 4395 UUAUAGAU CUGAUGAG X 3262 UAAUAACUU 4401 CGAA AGUUAUUA AUCUAUAA 4396 UUUAUAGA CUGAUGAG X 3263 AAUAACUUA 4402 CGAA AAGUUAUU UCUAUAAA WO 99/50403 PCT/US99/06507 192 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4398 AGUUUAUA CUGAUGAG X 3264 UAACUUAUC 4403 CGAA AUAAGUUA UAUAAACU 5 4400 AUAGUUUA CUGAUGAG X 3265 ACUUAUCUA 4404 CGAA AGAUAAGU UAAACUAU 4402 UUAUAGUU CUGAUGAG X 3266 UUAUCUAUA 4405 CGAA AUAGAUAA AACUAUAA 4407 AGAGGUUA CUGAUGAG X 3267 UAUAAACUA 4406 10 CGAA AGUUUAUA UAACCUCU 4409 GGAGAGGU CUGAUGAG X 3268 UAAACUAUA 4407 CGAA AUAGUUUA ACCUCUCC 4414 AUGAAGGA CUGAUGAG X 3269 UAUAACCUC 4408 CGAA AGGUUAUA UCCUUCAU 15 4416 UCAUGAAG CUGAUGAG X 3270 UAACCUCUC 4409 CGAA AGAGGUUA CUUCAUGA 4419 CUGUCAUG CUGAUGAG X 3271 CCUCUCCUU 4410 CGAA AGGAGAGG CAUGACAG 4420 GCUGUCAU CUGAUGAG X 3272 CUCUCCUUC 4411 20 CGAA AAGGAGAG AUGACAGC 4431 GUGGGGUG CUGAUGAG X 3273 GACAGCCUC 4412 CGAA AGGCUGUC CACCCCAC 4452 AUUUCUUA CUGAUGAG X 3274 CAAAAGGUU 4413 CGAA ACCUUUUG UAAGAAAU ~ 4453 UAUUUCUU CUGAUGAG X 3275 AAAAGGUUU 4414 CGAA AACCUUUU AAGAAAUA 4454 CUAUUUCU CUGAUGAG X 3276 AAAGGUUUA 4415 CGAA AAACCUUU AGAAAUAG 4461 UAUAAUUC CUGAUGAG X 3277 UAAGAAAUA 4416 30 CGAA AUUUCUUA GAAUUAUA 4466 ACAGUUAU CUGAUGAG X 3278 AAUAGAAUU 4417 CGAA AUUCUAUU AUAACUGU 4467 UACAGUUA CUGAUGAG X 3279 AUAGAAUUA 4418 CGAA AAUUCUAU UAACUGUA WO 99/50403 PCT/US99/06507 193 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4469 UUUACAGU CUGAUGAG X 3280 AGAAUUAUA 4419 CGAA AUAAUUCU ACUGUAAA 5 4475 AACAUCUU CUGAUGAG X 3281 AUAACUGUA 4420 CGAA ACAGUUAU AAGAUGUU 4483 CUGAAAUA CUGAUGAG X 3282 AAAGAUGUU 4421 CGAA ACAUCUUU UAUUUCAG 4484 CCUGAAAU CUGAUGAG X 3283 AAGAUGUUU 4422 10 CGAA AACAUCUU AUUUCAGG 4485 GCCUGAAA CUGAUGAG X 3284 AGAUGUUUA 4423 CGAA AAACAUCU UUUCAGGC 4487 AUGCCUGA CUGAUGAG X 3285 AUGUUUAUU 4424 CGAA AUAAACAU UCAGGCAU 15 4488 AAUGCCUG CUGAUGAG X 3286 UGUUUAUUU 4425 CGAA AAUAAACA CAGGCAUU 4489 CAAUGCCU CUGAUGAG X 3287 GUUUAUUUC 4426 CGAA AAAUAAAC AGGCAUUG 4496 AAAUAUCC CUGAUGAG X 3288 UCAGGCAUU 4427 20 CGAA AUGCCUGA GGAUAUUU 4501 GUAAAAAA CUGAUGAG X 3289 CAUUGGAUA 4428 CGAA AUCCAAUG UUUUUUAC 4503 AAGUAAAA CUGAUGAG X 3290 UUGGAUAUU 4429 CGAA AUAUCCAA UUUUACUU 25 4504 AAAGUAAA CUGAUGAG X 3291 UGGAUAUUU 4430 CGAA AAUAUCCA UUUACUUU 4505 UAAAGUAA CUGAUGAG X 3292 GGAUAUUUU 4431 CGAA AAAUAUCC UUACUUUA 4506 CUAAAGUA CUGAUGAG X 3293 GAUAUUUUU 4432 30 CGAA AAAAUAUC UACUUUAG 4507 UCUAAAGU CUGAUGAG X 3294 AUAUUUUUU 4433 CGAA AAAAAUAU ACUUUAGA 4508 UUCUAAAG CUGAUGAG X 3295 UAUUUUUUA 4434 CGAA AAAAAAUA CUUUAGAA WO 99/50403 PCTIUS99/06507 194 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4511 GGCUUCUA CUGAUGAG X 3296 UUUUUACUU 4435 CGAA AGUAAAAA UAGAAGCC 5 4512 AGGCUUCU CUGAUGAG X 3297 UUUUACUUU 4436 CGAA AAGUAAAA AGAAGCCU 4513 CAGGCUUC CUGAUGAG X 3298 UUUACUUUA 4437 CGAA AAAGUAAA GAAGCCUG 4525 AGAAACAU CUGAUGAG X 3299 GCCUGCAUA 4438 10 CGAA AUGCAGGC AUGUUUCU 4530 AAUCCAGA CUGAUGAG X 3300 CAUAAUGUU 4439 CGAA ACAUUAUG UCUGGAUU 4531 AAAUCCAG CUGAUGAG X 3301 AUAAUGUUU 4440 CGAA AACAUUAU CUGGAUUU 15 4532 UAAAUCCA CUGAUGAG X 3302 UAAUGUUUC 4441 CGAA AAACAUUA UGGAUUUA 4538 AGUAUGUA CUGAUGAG X 3303 UUCUGGAUU 4442 CGAA AUCCAGAA UACAUACU 4539 CAGUAUGU CUGAUGAG X 3304 UCUGGAUUU 4443 20 CGAA AAUCCAGA ACAUACUG 4540 ACAGUAUG CUGAUGAG X 3305 CUGGAUUUA 4444 CGAA AAAUCCAG CAUACUGU 4544 UGUUACAG CUGAUGAG X 3306 AUUUACAUA 4445 CGAA AUGUAAAU CUGUAACA 25 4549 CUGAAUGU CUGAUGAG X 3307 CAUACUGUA 4446 CGAA ACAGUAUG ACAUUCAG 4554 AAUUCCUG CUGAUGAG X 3308 UGUAACAUU 4447 CGAA AUGUUACA CAGGAAUU 4555 GAAUUCCU CUGAUGAG X 3309 GUAACAUUC 4448 30 CGAA AAUGUUAC AGGAAUUC 4562 UCUCCAAG CUGAUGAG X 3310 UCAGGAAUU 4449 CGAA AUUCCUGA CUUGGAGA 4563 UUCUCCAA CUGAUGAG X 3311 CAGGAAUUC 4450 CGAA AAUUCCUG UUGGAGAA WO 99/50403 PCT/US99/06507 195 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4565 UCUUCUCC CUGAUGAG X 3312 GGAAUUCUU 4451 CGAA AGAAUUCC GGAGAAGA 5 4579 AGUGAAUA CUGAUGAG X 3313 AGAUGGGUU 4452 CGAA ACCCAUCU UAUUCACU 4580 CAGUGAAU CUGAUGAG X 3314 GAUGGGUUU 4453 CGAA AACCCAUC AUUCACUG 4581 UCAGUGAA CUGAUGAG X 3315 AUGGGUUUA 4454 10 CGAA AAACCCAU UUCACUGA 4583 GUUCAGUG CUGAUGAG X 3316 GGGUUUAUU 4455 CGAA AUAAACCC CACUGAAC 4584 AGUUCAGU CUGAUGAG X 3317 GGUUUAUUC 4456 CGAA AAUAAACC ACUGAACU 15 4593 CCGCACUA CUGAUGAG X 3318 ACUGAACUC 4457 CGAA AGUUCAGU UAGUGCGG 4595 AACCGCAC CUGAUGAG X 3319 UGAACUCUA 4458 CGAA AGAGUUCA GUGCGGUU 4603 AGUGAGUA CUGAUGAG X 3320 AGUGCGGUU 4459 20 CGAA ACCGCACU UACUCACU 4604 CAGUGAGU CUGAUGAG X 3321 GUGCGGUUU 4460 CGAA AACCGCAC ACUCACUG 4605 GCAGUGAG CUGAUGAG X 3322 UGCGGUUUA 4461 CGAA AAACCGCA CUCACUGC 25 4608 GCAGCAGU CUGAUGAG X 3323 GGUUUACUC 4462 CGAA AGUAAACC ACUGCUGC 4621 AUAUACAG CUGAUGAG X 3324 CUGCAAAUA 4463 CGAA AUUUGCAG CUGUAUAU 4626 CCUGAAUA CUGAUGAG X 3325 AAUACUGUA 4464 30 CGAA ACAGUAUU UAUUCAGG 4628 GUCCUGAA CUGAUGAG X 3326 UACUGUAUA 4465 CGAA AUACAGUA UUCAGGAC 4630 AAGUCCUG CUGAUGAG X 3327 CUGUAUAUU 4466 CGAA AUAUACAG CAGGACUU WO 99/50403 PCT/US99/06507 196 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4631 CAAGUCCU CUGAUGAG X 3328 UGUAUAUUC 4467 CGAA AAUAUACA AGGACUUG 5 4638 UUUCUUUC CUGAUGAG X 3329 UCAGGACUU 4468 CGAA AGUCCUGA GAAAGAAA 4659 UAGUUCCA CUGAUGAG X 3330 GAAUGCCUA 4469 CGAA AGGCAUUC UGGAACUA 4667 GGAUCCAC CUGAUGAG X 3331 AUGGAACUA 4470 10 CGAA AGUUCCAU GUGGAUCC 4674 UCAGUUUG CUGAUGAG X 3332 UAGUGGAUC 4471 CGAA AUCCACUA CAAACUGA 4684 UUAUACUG CUGAUGAG X 3333 AAACUGAUC 4472 CGAA AUCAGUUU CAGUAUAA 15 4689 UAGUCUUA CUGAUGAG X 3334 GAUCCAGUA 4473 CGAA ACUGGAUC UAAGACUA 4691 AGUAGUCU CUGAUGAG X 3335 UCCAGUAUA 4474 CGAA AUACUGGA AGACUACU 4697 AGAUUCAG CUGAUGAG X 3336 AUAAGACUA 4475 20 CGAA AGUCUUAU CUGAAUCU 4704 UGGUAGCA CUGAUGAG X 3337 UACUGAAUC 4476 CGAA AUUCAGUA UGCUACCA 4709 UGUUUUGG CUGAUGAG X 3338 AAUCUGCUA 4477 CGAA AGCAGAUU CCAAAACA 25 4720 CACUGAUU CUGAUGAG X 3339 AAAACAGUU 4478 CGAA ACUGUUUU AAUCAGUG 4721 UCACUGAU CUGAUGAG X 3340 AAACAGUUA 4479 CGAA AACUGUUU AUCAGUGA 4724 GACUCACU CUGAUGAG X 3341 CAGUUAAUC 4480 30 CGAA AUUAACUG AGUGAGUC 4732 GAACACUC CUGAUGAG X 3342 CAGUGAGUC 4481 CGAA ACUCACUG GAGUGUUC 4739 AAAAAUAG CUGAUGAG X 3343 UCGAGUGUU 4482 CGAA ACACUCGA CUAUUUUU WO 99/50403 PCT/US99/06507 197 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4740 AAAAAAUA CUGAUGAG X 3344 CGAGUGUUC 4483 CGAA AACACUCG UAUUUUUU 5 4742 ACAAAAAA CUGAUGAG X 3345 AGUGUUCUA 4484 CGAA AGAACACU UUUUUUGU 4744 AAACAAAA CUGAUGAG X 3346 UGUUCUAUU 4485 CGAA AUAGAACA UUUUGUUU 4745 AAAACAAA CUGAUGAG X 3347 GUUCUAUUU 4486 10 CGAA AAUAGAAC UUUGUUUU 4746 CAAAACAA CUGAUGAG X 3348 UUCUAUUUU 4487 CGAA AAAUAGAA UUGUUUUG 4747 ACAAAACA CUGAUGAG X 3349 UCUAUUUUU 4488 CGAA AAAAUAGA UGUUUUGU 15 4748 AACAAAAC CUGAUGAG X 3350 CUAUUUUUU 4489 CGAA AAAAAUAG GUUUUGUU 4751 GGAAACAA CUGAUGAG X 3351 UUUUUUGUU 4490 CGAA ACAAAAAA UUGUUUCC 4752 AGGAAACA CUGAUGAG X 3352 UUUUUGUUU 4491 20 CGAA AACAAAAA UGUUUCCU 4753 GAGGAAAC CUGAUGAG X 3353 UUUUGUUUU 4492 CGAA AAACAAAA GUUUCCUC 4756 GGGGAGGA CUGAUGAG X 3354 UGUUUUGUU 4493 CGAA ACAAAACA UCCUCCCC 25 4757 AGGGGAGG CUGAUGAG X 3355 GUUUUGUUU 4494 CGAA AACAAAAC CCUCCCCU 4758 UAGGGGAG CUGAUGAG X 3356 UUUUGUUUC 4495 CGAA AAACAAAA CUCCCCUA 4761 AGAUAGGG CUGAUGAG X 3357 UGUUUCCUC 4496 30 CGAA AGGAAACA CCCUAUCU 4766 AAUACAGA CUGAUGAG X 3358 CCUCCCCUA 4497 CGAA AGGGGAGG UCUGUAUU 4768 GGAAUACA CUGAUGAG X 3359 UCCCCUAUC 4498 CGAA AUAGGGGA UGUAUUCC WO 99/50403 PCTIUS99/06507 198 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4772 UUUGGGAA CUGAUGAG X 3360 CUAUCUGUA 4499 CGAA ACAGAUAG UUCCCAAA 4774 UUUUUGGG CUGAUGAG X 3361 AUCUGUAUU 4500 CGAA AUACAGAU CCCAAAAA 4775 AUUUUUGG CUGAUGAG X 3362 UCUGUAUUC 4501 CGAA AAUACAGA CCAAAAAU 4784 CCCAAAGU CUGAUGAG X 3363 CCAAAAAUU 4502 0 CGAA AUUUUUGG ACUUUGGG 4785 CCCCAAAG CUGAUGAG X 3364 CAAAAAUUA 4503 CGAA AAUUUUUG CUUUGGGG 4788 UAGCCCCA CUGAUGAG X 3365 AAAUUACUU 4504 CGAA AGUAAUUU UGGGGCUA 5 4789 UUAGCCCC CUGAUGAG X 3366 AAUUACUUU 4505 CGAA AAGUAAUU GGGGCUAA 4796 UGUUAAAU CUGAUGAG X 3367 UUGGGGCUA 4506 CGAA AGCCCCAA AUUUAACA 4799 UCUUGUUA CUGAUGAG X 3368 GGGCUAAUU 4507 0 CGAA AUUAGCCC UAACAAGA 4800 UUCUUGUU CUGAUGAG X 3369 GGCUAAUUU 4508 CGAA AAUUAGCC AACAAGAA 4801 GUUCUUGU CUGAUGAG X 3370 GCUAAUUUA 4509 CGAA AAAUUAGC ACAAGAAC 5 4811 ACAAUUUA CUGAUGAG X 3371 CAAGAACUU 4510 CGAA AGUUCUUG UAAAUUGU 4812 CACAAUUU CUGAUGAG X 3372 AAGAACUUU 4511 CGAA AAGUUCUU AAAUUGUG 4813 ACACAAUU CUGAUGAG X 3373 AGAACUUUA 4512 0 CGAA AAAGUUCU AAUUGUGU 4817 UAAAACAC CUGAUGAG X 3374 CUUUAAAUU 4513 CGAA AUUUAAAG GUGUUUUA 4822 ACAAUUAA CUGAUGAG X 3375 AAUUGUGUU 4514 CGAA ACACAAUU UUAAUUGU WO 99/50403 PCT/US99/06507 199 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4823 UACAAUUA CUGAUGAG X 3376 AUUGUGUUU 4515 CGAA AACACAAU UAAUUGUA 4824 UUACAAUU CUGAUGAG X 3377 UUGUGUUUU 4516 CGAA AAACACAA AAUUGUAA 4825 UUUACAAU CUGAUGAG X 3378 UGUGUUUUA 4517 CGAA AAAACACA AUUGUAAA 4828 AUUUUUAC CUGAUGAG X 3379 GUUUUAAUU 4518 0 CGAA AUUAAAAC GUAAAAAU 4831 GCCAUUUU CUGAUGAG X 3380 UUAAUUGUA 4519 CGAA ACAAUUAA AAAAUGGC 4852 AGAGUAAU CUGAUGAG X 3381 GGUGGAAUU 4520 CGAA AUUCCACC AUUACUCU 5 4853 UAGAGUAA CUGAUGAG X 3382 GUGGAAUUA 4521 CGAA AAUUCCAC UUACUCUA 4855 UAUAGAGU CUGAUGAG X 3383 GGAAUUAUU 4522 CGAA AUAAUUCC ACUCUAUA 4856 GUAUAGAG CUGAUGAG X 3384 GAAUUAUUA 4523 0 CGAA AAUAAUUC CUCUAUAC 4859 AAUGUAUA CUGAUGAG X 3385 UUAUUACUC 4524 CGAA AGUAAUAA UAUACAUU 4861 UGAAUGUA CUGAUGAG X 3386 AUUACUCUA 4525 CGAA AGAGUAAU UACAUUCA 5 4863 GUUGAAUG CUGAUGAG X 3387 UACUCUAUA 4526 CGAA AUAGAGUA CAUUCAAC 4867 CUCUGUUG CUGAUGAG X 3388 CUAUACAUU 4527 CGAA AUGUAUAG CAACAGAG 4868 UCUCUGUU CUGAUGAG X 3389 UAUACAUUC 4528 0 CGAA AAUGUAUA AACAGAGA 4883 UUCAUAUC CUGAUGAG X 3390 GACUGAAUA 4529 CGAA AUUCAGUC GAUAUGAA 4887 AGCUUUCA CUGAUGAG X 3391 GAAUAGAUA 4530 CGAA AUCUAUUC UGAAAGCU WO 99/50403 PCT/US99/06507 200 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4899 UUAAAAAA CUGAUGAG X 3392 AAGCUGAUU 4531 CGAA AUCAGCUU UUUUUUAA 4900 AUUAAAAA CUGAUGAG X 3393 AGCUGAUUU 4532 CGAA AAUCAGCU UUUUUAAU 4901 AAUUAAAA CUGAUGAG X 3394 GCUGAUUUU 4533 CGAA AAAUCAGC UUUUAAUU 4902 UAAUUAAA CUGAUGAG X 3395 CUGAUUUUU 4534 0 CGAA AAAAUCAG UUUAAUUA 4903 GUAAUUAA CUGAUGAG X 3396 UGAUUUUUU 4535 CGAA AAAAAUCA UUAAUUAC 4904 GGUAAUUA CUGAUGAG X 3397 GAUUUUUUU 4536 CGAA AAAAAAUC UAAUUACC 5 4905 UGGUAAUU CUGAUGAG X 3398 AUUUUUUUU 4537 CGAA AAAAAAAU AAUUACCA 4906 AUGGUAAU CUGAUGAG X 3399 UUUUUUUUA 4538 CGAA AAAAAAAA AUUACCAU 4909 AGCAUGGU CUGAUGAG X 3400 UUUUUAAUU 4539 0 CGAA AUUAAAAA ACCAUGCU 4910 AAGCAUGG CUGAUGAG X 3401 UUUUAAUUA 4540 CGAA AAUUAAAA CCAUGCUU 4918 ACAUUGUG CUGAUGAG X 3402 ACCAUGCUU 4541 CGAA AGCAUGGU CACAAUGU 5 4919 AACAUUGU CUGAUGAG X 3403 CCAUGCUUC 4542 CGAA AAGCAUGG ACAAUGUU 4927 UAUAACUU CUGAUGAG X 3404 CACAAUGUU 4543 CGAA ACAUUGUG AAGUUAUA 4928 AUAUAACU CUGAUGAG X 3405 ACAAUGUUA 4544 0 CGAA AACAUUGU AGUUAUAU 4932 CCCCAUAU CUGAUGAG X 3406 UGUUAAGUU 4545 CGAA ACUUAACA AUAUGGGG 4933 UCCCCAUA CUGAUGAG X 3407 GUUAAGUUA 4546 CGAA AACUUAAC UAUGGGGA WO 99/50403 PCT/US99/06507 201 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 4935 GCUCCCCA CUGAUGAG X 3408 UAAGUUAUA 4547 CGAA AUAACUUA UGGGGAGC 4961 AAACAAAU CUGAUGAG X 3409 CAGGUGCUA 4548 CGAA AGCACCUG AUUUGUUU 4964 CCAAAACA CUGAUGAG X 3410 GUGCUAAUU 4549 CGAA AUUAGCAC UGUUUUGG 4965 UCCAAAAC CUGAUGAG X 3411 UGCUAAUUU 4550 0 CGAA AAUUAGCA GUUUUGGA 4968 AUAUCCAA CUGAUGAG X 3412 UAAUUUGUU 4551 CGAA ACAAAUUA UUGGAUAU 4969 UAUAUCCA CUGAUGAG X 3413 AAUUUGUUU 4552 CGAA AACAAAUU UGGAUAUA 5 4970 CUAUAUCC CUGAUGAG X 3414 AUUUGUUUU 4553 CGAA AAACAAAU GGAUAUAG 4975 UUAUACUA CUGAUGAG X 3415 UUUUGGAUA 4554 CGAA AUCCAAAA UAGUAUAA 4977 GCUUAUAC CUGAUGAG X 3416 UUGGAUAUA 4555 0 CGAA AUAUCCAA GUAUAAGC 4980 ACUGCUUA CUGAUGAG X 3417 GAUAUAGUA 4556 CGAA ACUAUAUC UAAGCAGU 4982 ACACUGCU CUGAUGAG X 3418 UAUAGUAUA 4557 CGAA AUACUAUA AGCAGUGU 5 4991 AAAACACA CUGAUGAG X 3419 AGCAGUGUC 4558 CGAA ACACUGCU UGUGUUUU 4997 UCUUUCAA CUGAUGAG X 3420 GUCUGUGUU 4559 CGAA ACACAGAC UUGAAAGA 4998 UUCUUUCA CUGAUGAG X 3421 UCUGUGUUU 4560 0 CGAA AACACAGA UGAAAGAA 4999 AUUCUUUC CUGAUGAG X 3422 CUGUGUUUU 4561 CGAA AAACACAG GAAAGAAU 5008 CUGUGUUC CUGAUGAG X 3423 GAAAGAAUA 4562 CGAA AUUCUUUC GAACACAG WO 99/50403 PCT/US99/06507 202 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5018 GCACUACA CUGAUGAG X 3424 AACACAGUU 4563 CGAA ACUGUGUU UGUAGUGC 5 5019 GGCACUAC CUGAUGAG X 3425 ACACAGUUU 4564 CGAA AACUGUGU GUAGUGCC 5022 AGUGGCAC CUGAUGAG X 3426 CAGUUUGUA 4565 CGAA ACAAACUG GUGCCACU 5033 CCCAAAAC CUGAUGAG X 3427 GCCACUGUU 4566 10 CGAA ACAGUGGC GUUUUGGG 5036 CCCCCCAA CUGAUGAG X 3428 ACUGUUGUU 4567 CGAA ACAACAGU UUGGGGGG 5037 CCCCCCCA CUGAUGAG X 3429 CUGUUGUUU 4568 CGAA AACAACAG UGGGGGGG 15 5038 CCCCCCCC CUGAUGAG X 3430 UGUUGUUUU 4569 CGAA AAACAACA GGGGGGGG 5049 AAGAAAAA CUGAUGAG X 3431 GGGGGGCUU 4570 CGAA AGCCCCCC UUUUUCUU 5050 AAAGAAAA CUGAUGAG X 3432 GGGGGCUUU 4571 20 CGAA AAGCCCCC UUUUCUUU 5051 AAAAGAAA CUGAUGAG X 3433 GGGGCUUUU 4572 CGAA AAAGCCCC UUUCUUUU 5052 AAAAAGAA CUGAUGAG X 3434 GGGCUUUUU 4573 CGAA AAAAGCCC UUCUUUUU 25 5053 GAAAAAGA CUGAUGAG X 3435 GGCUUUUUU 4574 CGAA AAAAAGCC UCUUUUUC 5054 GGAAAAAG CUGAUGAG X 3436 GCUUUUUUU 4575 CGAA AAAAAAGC CUUUUUCC 5055 CGGAAAAA CUGAUGAG X 3437 CUUUUUUUC 4576 30 CGAA AAAAAAAG UUUUUCCG 5057 UCCGGAAA CUGAUGAG X 3438 UUUUUUCUU 4577 CGAA AGAAAAAA UUUCCGGA 5058 UUCCGGAA CUGAUGAG X 3439 UUUUUCUUU 4578 CGAA AAGAAAAA UUCCGGAA WO 99/50403 PCT/US99/06507 203 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5059 UUUCCGGA CUGAUGAG X 3440 UUUUCUUUU 4579 CGAA AAAGAAAA UCCGGAAA 5 5060 UUUUCCGG CUGAUGAG X 3441 UUUCUUUUU 4580 CGAA AAAAGAAA CCGGAAAA 5061 AUUUUCCG CUGAUGAG X 3442 UUCUUUUUC 4581 CGAA AAAAAGAA CGGAAAAU 5070 GGUUUAAG CUGAUGAG X 3443 CGGAAAAUC 4582 10 CGAA AUUUUCCG CUUAAACC 5073 UAAGGUUU CUGAUGAG X 3444 AAAAUCCUU 4583 CGAA AGGAUUUU AAACCUUA 5074 UUAAGGUU CUGAUGAG X 3445 AAAUCCUUA 4584 CGAA AAGGAUUU AACCUUAA 15 5080 AGUAUCUU CUGAUGAG X 3446 UUAAACCUU 4585 CGAA AGGUUUAA AAGAUACU 5081 UAGUAUCU CUGAUGAG X 3447 UAAACCUUA 4586 CGAA AAGGUUUA AGAUACUA 5086 GUCCUUAG CUGAUGAG X 3448 CUUAAGAUA 4587 20 CGAA AUCUUAAG CUAAGGAC 5089 AACGUCCU CUGAUGAG X 3449 AAGAUACUA 4588 CGAA AGUAUCUU AGGACGUU 5097 ACCAAAAC CUGAUGAG X 3450 AAGGACGUU 4589 CGAA ACGUCCUU GUUUUGGU 25 5100 ACAACCAA CUGAUGAG X 3451 GACGUUGUU 4590 CGAA ACAACGUC UUGGUUGU 5101 UACAACCA CUGAUGAG X 3452 ACGUUGUUU 4591 CGAA AACAACGU UGGUUGUA 5102 GUACAACC CUGAUGAG X 3453 CGUUGUUUU 4592 30 CGAA AAACAACG GGUUGUAC 5106 CCAAGUAC CUGAUGAG X 3454 GUUUUGGUU 4593 CGAA ACCAAAAC GUACUUGG 5109 AUUCCAAG CUGAUGAG X 3455 UUGGUUGUA 4594 CGAA ACAACCAA CUUGGAAU WO 99/50403 PCT/US99/06507 204 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5112 AGAAUUCC CUGAUGAG X 3456 GUUGUACUU 4595 CGAA AGUACAAC GGAAUUCU 5 5118 UGACUAAG CUGAUGAG X 3457 CUUGGAAUU 4596 CGAA AUUCCAAG CUUAGUCA 5119 GUGACUAA CUGAUGAG X 3458 UUGGAAUUC 4597 CGAA AAUUCCAA UUAGUCAC 5121 UUGUGACU CUGAUGAG X 3459 GGAAUUCUU 4598 10 CGAA AGAAUUCC AGUCACAA 5122 UUUGUGAC CUGAUGAG X 3460 GAAUUCUUA 4599 CGAA AAGAAUUC GUCACAAA 5125 UAUUUUGU CUGAUGAG X 3461 UUCUUAGUC 4600 CGAA ACUAAGAA ACAAAAUA 15 5133 ACAAAAUA CUGAUGAG X 3462 CACAAAAUA 4601 CGAA AUUUUGUG UAUUUUGU 5135 AAACAAAA CUGAUGAG X 3463 CAAAAUAUA 4602 CGAA AUAUUUUG UUUUGUUU 5137 GUAAACAA CUGAUGAG X 3464 AAAUAUAUU 4603 20 CGAA AUAUAUUU UUGUUUAC 5138 UGUAAACA CUGAUGAG X 3465 AAUAUAUUU 4604 CGAA AAUAUAUU UGUUUACA 5139 UUGUAAAC CUGAUGAG X 3466 AUAUAUUUU 4605 CGAA AAAUAUAU GUUUACAA 25 5142 UUUUUGUA CUGAUGAG X 3467 UAUUUUGUU 4606 CGAA ACAAAAUA UACAAAAA 5143 AUUUUUGU CUGAUGAG X 3468 AUUUUGUUU 4607 CGAA AACAAAAU ACAAAAAU 5144 AAUUUUUG CUGAUGAG X 3469 UUUUGUUUA 4608 30 CGAA AAACAAAA CAAAAAUU 5152 UUUACAGA CUGAUGAG X 3470 ACAAAAAUU 4609 CGAA AUUUUUGU UCUGUAAA 5153 UUUUACAG CUGAUGAG X 3471 CAAAAAUUU 4610 CGAA AAUUUUUG CUGUAAAA WO 99/50403 PCT/US99/06507 205 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5154 GUUUUACA CUGAUGAG X 3472 AAAAAUUUC 4611 CGAA AAAUUUUU UGUAAAAC 5 5158 ACCUGUUU CUGAUGAG X 3473 AUUUCUGUA 4612 CGAA ACAGAAAU AAACAGGU 5167 ACUGUUAU CUGAUGAG X 3474 AAACAGGUU 4613 CGAA ACCUGUUU AUAACAGU 5168 CACUGUUA CUGAUGAG X 3475 AACAGGUUA 4614 10 CGAA AACCUGUU UAACAGUG 5170 AACACUGU CUGAUGAG X 3476 CAGGUUAUA 4615 CGAA AUAACCUG ACAGUGUU 5178 AGACUUUA CUGAUGAG X 3477 AACAGUGUU 4616 CGAA ACACUGUU UAAAGUCU 15 5179 GAGACUUU CUGAUGAG X 3478 ACAGUGUUU 4617 CGAA AACACUGU AAAGUCUC 5180 UGAGACUU CUGAUGAG X 3479 CAGUGUUUA 4618 CGAA AAACACUG AAGUCUCA 5185 GAAACUGA CUGAUGAG X 3480 UUUAAAGUC 4619 20 CGAA ACUUUAAA UCAGUUUC 5187 AAGAAACU CUGAUGAG X 3481 UAAAGUCUC 4620 CGAA AGACUUUA AGUUUCUU 5191 AAGCAAGA CUGAUGAG X 3482 GUCUCAGUU 4621 CGAA ACUGAGAC UCUUGCUU 25 5192 CAAGCAAG CUGAUGAG X 3483 UCUCAGUUU 4622 CGAA AACUGAGA CUUGCUUG 5193 CCAAGCAA CUGAUGAG X 3484 CUCAGUUUC 4623 CGAA AAACUGAG UUGCUUGG 5195 CCCCAAGC CUGAUGAG X 3485 CAGUUUCUU 4624 30 CGAA AGAAACUG GCUUGGGG 5199 AGUUCCCC CUGAUGAG X 3486 UUCUUGCUU 4625 CGAA AGCAAGAA GGGGAACU 5208 AGGGACAC CUGAUGAG X 3487 GGGGAACUU 4626 CGAA AGUUCCCC GUGUCCCU WO 99/50403 PCT/US99/06507 206 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5213 ACAUUAGG CUGAUGAG X 3488 ACUUGUGUC 4627 CGAA ACACAAGU CCUAAUGU 5 5217 UAACACAU CUGAUGAG X 3489 GUGUCCCUA 4628 CGAA AGGGACAC AUGUGUUA 5224 AGCAAUCU CUGAUGAG X 3490 UAAUGUGUU 4629 CGAA ACACAUUA AGAUUGCU 5225 UAGCAAUC CUGAUGAG X 3491 AAUGUGUUA 4630 10 CGAA AACACAUU GAUUGCUA 5229 AAUCUAGC CUGAUGAG X 3492 UGUUAGAUU 4631 CGAA AUCUAACA GCUAGAUU 5233 UAGCAAUC CUGAUGAG X 3493 AGAUUGCUA 4632 CGAA AGCAAUCU GAUUGCUA 15 5237 UCCUUAGC CUGAUGAG X 3494 UGCUAGAUU 4633 CGAA AUCUAGCA GCUAAGGA 5241 CAGCUCCU CUGAUGAG X 3495 AGAUUGCUA 4634 CGAA AGCAAUCU AGGAGCUG 5252 CUGUCAAG CUGAUGAG X 3496 GAGCUGAUA 4635 20 CGAA AUCAGCUC CUUGACAG 5255 AAACUGUC CUGAUGAG X 3497 CUGAUACUU 4636 CGAA AGUAUCAG GACAGUUU 5262 GUCUAAAA CUGAUGAG X 3498 UUGACAGUU 4637 CGAA ACUGUCAA UUUUAGAC 25 5263 GGUCUAAA CUGAUGAG X 3499 UGACAGUUU 4638 CGAA AACUGUCA UUUAGACC 5264 AGGUCUAA CUGAUGAG X 3500 GACAGUUUU 4639 CGAA AAACUGUC UUAGACCU 5265 CAGGUCUA CUGAUGAG X 3501 ACAGUUUUU 4640 30 CGAA AAAACUGU UAGACCUG 5266 ACAGGUCU CUGAUGAG X 3502 CAGUUUUUU 4641 CGAA AAAAACUG AGACCUGU 5267 CACAGGUC CUGAUGAG X 3503 AGUUUUUUA 4642 CGAA AAAAAACU GACCUGUG WO 99/50403 PCTIUS99/06507 207 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5277 UUUUUAGU CUGAUGAG X 3504 ACCUGUGUU 4643 CGAA ACACAGGU ACUAAAAA 5 5278 UUUUUUAG CUGAUGAG X 3505 CCUGUGUUA 4644 CGAA AACACAGG CUAAAAAA 5281 CUUUUUUU CUGAUGAG X 3506 GUGUUACUA 4645 CGAA AGUAACAC AAAAAAAG 5298 CCUUUUCC CUGAUGAG X 3507 AUGAAUGUC 4646 10 CGAA ACAUUCAU GGAAAAGG 5311 ACCCUCCC CUGAUGAG X 3508 AAGGGUGUU 4647 CGAA ACACCCUU GGGAGGGU 5323 UCUUUGUU CUGAUGAG X 3509 AGGGUGGUC 4648 CGAA ACCACCCU AACAAAGA 15 5343 AACACCAU CUGAUGAG X 3510 AAAGAUGUU 4649 CGAA ACAUCUUU AUGGUGUU 5344 AAACACCA CUGAUGAG X 3511 AAGAUGUUA 4650 CGAA AACAUCUU UGGUGUUU 5351 UAAGUCUA CUGAUGAG X 3512 UAUGGUGUU 4651 20 CGAA ACACCAUA UAGACUUA 5352 AUAAGUCU CUGAUGAG X 3513 AUGGUGUUU 4652 CGAA AACACCAU AGACUUAU 5353 CAUAAGUC CUGAUGAG X 3514 UGGUGUUUA 4653 CGAA AAACACCA GACUUAUG 25 5358 ACAACCAU CUGAUGAG X 3515 UUUAGACUU 4654 CGAA AGUCUAAA AUGGUUGU 5359 AACAACCA CUGAUGAG X 3516 UUAGACUUA 4655 CGAA AAGUCUAA UGGUUGUU 5364 UUUUUAAC CUGAUGAG X 3517 CUUAUGGUU 4656 30 CGAA ACCAUAAG GUUAAAAA 5367 ACAUUUUU CUGAUGAG X 3518 AUGGUUGUU 4657 CGAA ACAACCAU AAAAAUGU 5368 GACAUUUU CUGAUGAG X 3519 UGGUUGUUA 4658 CGAA AACAACCA AAAAUGUC WO 99/50403 PCT/US99/06507 208 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5376 CUUGAGAU CUGAUGAG X 3520 AAAAAUGUC 4659 CGAA ACAUUUUU AUCUCAAG 5 5379 UGACUUGA CUGAUGAG X 3521 AAUGUCAUC 4660 CGAA AUGACAUU UCAAGUCA 5381 CUUGACUU CUGAUGAG X 3522 UGUCAUCUC 4661 CGAA AGAUGACA AAGUCAAG 5386 AGUGACUU CUGAUGAG X 3523 UCUCAAGUC 4662 10 CGAA ACUUGAGA AAGUCACU 5391 AGACCAGU CUGAUGAG X 3524 AGUCAAGUC 4663 CGAA ACUUGACU ACUGGUCU 5398 UGCAAACA CUGAUGAG X 3525 UCACUGGUC 4664 CGAA ACCAGUGA UGUUUGCA 15 5402 CAAAUGCA CUGAUGAG X 3526 UGGUCUGUU 4665 CGAA ACAGACCA UGCAUUUG 5403 UCAAAUGC CUGAUGAG X 3527 GGUCUGUUU 4666 CGAA AACAGACC GCAUUUGA 5408 AUGUAUCA CUGAUGAG X 3528 GUUUGCAUU 4667 20 CGAA AUGCAAAC UGAUACAU 5409 AAUGUAUC CUGAUGAG X 3529 UUUGCAUUU 4668 CGAA AAUGCAAA GAUACAUU 5413 CAAAAAUG CUGAUGAG X 3530 CAUUUGAUA 4669 CGAA AUCAAAUG CAUUUUUG 25 5417 AGUACAAA CUGAUGAG X 3531 UGAUACAUU 4670 CGAA AUGUAUCA UUUGUACU 5418 UAGUACAA CUGAUGAG X 3532 GAUACAUUU 4671 CGAA AAUGUAUC UUGUACUA 5419 UUAGUACA CUGAUGAG X 3533 AUACAUUUU 4672 30 CGAA AAAUGUAU UGUACUAA 5420 GUUAGUAC CUGAUGAG X 3534 UACAUUUUU 4673 CGAA AAAAUGUA GUACUAAC 5423 CUAGUUAG CUGAUGAG X 3535 AUUUUUGUA 4674 CGAA ACAAAAAU CUAACUAG WO 99/50403 PCTIUS99/06507 209 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5426 AUGCUAGU CUGAUGAG X 3536 UUUGUACUA 4675 CGAA AGUACAAA ACUAGCAU 5 5430 UACAAUGC CUGAUGAG X 3537 UACUAACUA 4676 CGAA AGUUAGUA GCAUUGUA 5435 AAUUUUAC CUGAUGAG X 3538 ACUAGCAUU 4677 CGAA AUGCUAGU GUAAAAUU 5438 AAUAAUUU CUGAUGAG X 3539 AGCAUUGUA 4678 10 CGAA ACAAUGCU AAAUUAUU 5443 CAUGAAAU CUGAUGAG X 3540 UGUAAAAUU 4679 CGAA AUUUUACA AUUUCAUG 5444 UCAUGAAA CUGAUGAG X 3541 GUAAAAUUA 4680 CGAA AAUUUUAC UUUCAUGA 15 5446 AAUCAUGA CUGAUGAG X 3542 AAAAUUAUU 4681 CGAA AUAAUUUU UCAUGAUU 5447 UAAUCAUG CUGAUGAG X 3543 AAAUUAUUU 4682 CGAA AAUAAUUU CAUGAUUA 5448 CUAAUCAU CUGAUGAG X 3544 AAUUAUUUC 4683 20 CGAA AAAUAAUU AUGAUUAG 5454 UAAUUUCU CUGAUGAG X 3545 UUCAUGAUU 4684 CGAA AUCAUGAA AGAAAUUA 5455 GUAAUUUC CUGAUGAG X 3546 UCAUGAUUA 4685 CGAA AAUCAUGA GAAAUUAC 25 5461 CCACAGGU CUGAUGAG X 3547 UUAGAAAUU 4686 CGAA AUUUCUAA ACCUGUGG 5462 UCCACAGG CUGAUGAG X 3548 UAGAAAUUA 4687 CGAA AAUUUCUA CCUGUGGA 5472 UAUACAAA CUGAUGAG X 3549 CUGUGGAUA 4688 30 CGAA AUCCACAG UUUGUAUA 5474 UUUAUACA CUGAUGAG X 3550 GUGGAUAUU 4689 CGAA AUAUCCAC UGUAUAAA 5475 UUUUAUAC CUGAUGAG X 3551 UGGAUAUUU 4690 CGAA AAUAUCCA GUAUAAAA WO 99/50403 PCT/US99/06507 210 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5478 CACUUUUA CUGAUGAG X 3552 AUAUUUGUA 4691 CGAA ACAAAUAU UAAAAGUG 5 5480 CACACUUU CUGAUGAG X 3553 AUUUGUAUA 4692 CGAA AUACAAAU AAAGUGUG 5493 AAAAAAUU CUGAUGAG X 3554 UGUGAAAUA 4693 CGAA AUUUCACA AAUUUUUU 5497 UUAUAAAA CUGAUGAG X 3555 AAAUAAAUU 4694 10 CGAA AUUUAUUU UUUUAUAA 5498 UUUAUAAA CUGAUGAG X 3556 AAUAAAUUU 4695 CGAA AAUUUAUU UUUAUAAA 5499 UUUUAUAA CUGAUGAG X 3557 AUAAAUUUU 4696 CGAA AAAUUUAU UUAUAAAA 15 5500 CUUUUAUA CUGAUGAG X 3558 UAAAUUUUU 4697 CGAA AAAAUUUA UAUAAAAG 5501 ACUUUUAU CUGAUGAG X 3559 AAAUUUUUU 4698 CGAA AAAAAUUU AUAAAAGU 5502 CACUUUUA CUGAUGAG X 3560 AAUUUUUUA 4699 20 CGAA AAAAAAUU UAAAAGUG 5504 AACACUUU CUGAUGAG X 3561 UUUUUUAUA 4700 CGAA AUAAAAAA AAAGUGUU 5512 AAACAAUG CUGAUGAG X 3562 AAAAGUGUU 4701 CGAA ACACUUUU CAUUGUUU 25 5513 GAAACAAU CUGAUGAG X 3563 AAAGUGUUC 4702 CGAA AACACUUU AUUGUUUC 5516 UACGAAAC CUGAUGAG X 3564 GUGUUCAUU 4703 CGAA AUGAACAC GUUUCGUA 5519 UGUUACGA CUGAUGAG X 3565 UUCAUUGUU 4704 30 CGAA ACAAUGAA UCGUAACA 5520 GUGUUACG CUGAUGAG X 3566 UCAUUGUUU 4705 CGAA AACAAUGA CGUAACAC 5521 UGUGUUAC CUGAUGAG X 3567 CAUUGUUUC 4706 CGAA AAACAAUG GUAACACA WO 99/50403 PCT/US99/06507 211 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5524 UGCUGUGU CUGAUGAG X 3568 UGUUUCGUA 4707 CGAA ACGAAACA ACACAGCA 5 5534 ACAUAUAC CUGAUGAG X 3569 CACAGCAUU 4708 CGAA AUGCUGUG GUAUAUGU 5537 UUCACAUA CUGAUGAG X 3570 AGCAUUGUA 4709 CGAA ACAAUGCU UAUGUGAA 5539 GCUUCACA CUGAUGAG X 3571 CAUUGUAUA 4710 10 CGAA AUACAAUG UGUGAAGC 5553 UAAUUUUA CUGAUGAG X 3572 AGCAAACUC 4711 CGAA AGUUUGCU UAAAAUUA 5555 UAUAAUUU CUGAUGAG X 3573 CAAACUCUA 4712 CGAA AGAGUUUG AAAUUAUA 15 5560 UCAUUUAU CUGAUGAG X 3574 UCUAAAAUU 4713 CGAA AUUUUAGA AUAAAUGA 5561 GUCAUUUA CUGAUGAG X 3575 CUAAAAUUA 4714 CGAA AAUUUUAG UAAAUGAC 5563 UUGUCAUU CUGAUGAG X 3576 AAAAUUAUA 4715 20 CGAA AUAAUUUU AAUGACAA 5579 AAAUAGAU CUGAUGAG X 3577 ACCUGAAUU 4716 CGAA AUUCAGGU AUCUAUUU 5580 GAAAUAGA CUGAUGAG X 3578 CCUGAAUUA 4717 CGAA AAUUCAGG UCUAUUUC 25 5582 AUGAAAUA CUGAUGAG X 3579 UGAAUUAUC 4718 CGAA AUAAUUCA UAUUUCAU 5584 UGAUGAAA CUGAUGAG X 3580 AAUUAUCUA 4719 CGAA AGAUAAUU UUUCAUCA 5586 UUUGAUGA CUGAUGAG X 3581 UUAUCUAUU 4720 30 CGAA AUAGAUAA UCAUCAAA 5587 UUUUGAUG CUGAUGAG X 3582 UAUCUAUUU 4721 CGAA AAUAGAUA CAUCAAAA 5588 UUUUUGAU CUGAUGAG X 3583 AUCUAUUUC 4722 CGAA AAAUAGAU AUCAAAAA WO 99/50403 PCT/US99/06507 212 Seq. I.D. Seq. I.D. Position RZ No. Substrate No. 5591 UUUUUUUU CUGAUGAG X 3584 UAUUUCAUC 4723 CGAA AUGAAAUA AAAAAAAA 5 5614 UGCCCAUA CUGAUGAG X 3585 AAAAAACUU 4724 CGAA AGUUUUUU UAUGGGCA 5615 GUGCCCAU CUGAUGAG X 3586 AAAAACUUU 4725 CGAA AAGUUUUU AUGGGCAC 5616 UGUGCCCA CUGAUGAG X 3587 AAAACUUUA 4726 10 CGAA AAAGUUUU UGGGCACA 15 20 25 30 WO 99/50403 PCT/US99/06507 213 TABLE VIII: HAIRPIN RIBOZYME AND TARGET SEQUENCES FOR INTEGRIN ALPHA 6 SUBUNIT Seq. I.D. Seq. I.D. Position RZ No. Substrate No 8 CCCCGG AGAA GUCG 4727 CGACC GUC 4821 ACCAGAGAAACA X CCGGGG 5 GUACAUUACCUGGUA 60 UGCUGC AGAA GCAG 4728 CUGCG GUA 4822 ACCAGAGAAACA X GCAGCA GUACAUUACCUGGUA 77 GUCCGA AGAA GCCG 4729 CGGCA GCC 4823 10 ACCAGAGAAACA X UCGGAC GUACAUUACCUGGUA 83 GGCUGG AGAA GAGG 4730 CCUCG GAC 4824 ACCAGAGAAACA X CCAGCC GUACAUUACCUGGUA 15 89 GCUCCG AGAA GGGU 4731 ACCCA GCC 4825 ACCAGAGAAACA X CGGAGC GUACAUUACCUGGUA 106 UGCAGC AGAA GCCC 4732 GGGCG GCC 4826 ACCAGAGAAACA X GCUGCA 20 GUACAUUACCUGGUA 109 ACCUGC AGAA GCCG 4733 CGGCC GCU 4827 ACCAGAGAAACA X GCAGGU GUACAUUACCUGGUA 122 GAGGGG AGAA GGGA 4734 UCCCC GCU 4828 25 ACCAGAGAAACA X CCCCUC GUACAUUACCUGGUA 142 GCCAUG AGAA GACG 4735 CGUCC GCC 4829 ACCAGAGAAACA X CAUGGC GUACAUUACCUGGUA 30 152 CCCGGC AGAA GCCA 4736 UGGCC GCC 4830 ACCAGAGAAACA X GCCGGG GUACAUUACCUGGUA I _I__ WO 99/50403 PCT/US99/06507 214 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 155 CUGCCC AGAA GCGG 4737 CCGCC GCC 4831 ACCAGAGAAACA X GGGCAG 5 _GUACAUUACCUGGUA 163 AAGCAC AGAA GCCC 4738 GGGCA GCU 4832 ACCAGAGAAACA X GUGCUU GUACAUUACCUGGUA 181 CCCGCC AGAA GGUA 4739 UACCU GUC 4833 10 ACCAGAGAAACA X GGCGGG GUACAUUACCUGGUA 196 AGCCGG AGAA GGAG 4740 CUCCU GUC 4834 ACCAGAGAAACA X CCGGCU GUACAUUACCUGGUA 15 202 GCGCCG AGAA GGGA 4741 UCCCG GCU 4835 ACCAGAGAAACA X CGGCGC GUACAUUACCUGGUA 212 GUUGAA AGAA GCGC 4742 GCGCA GCC 4836 ACCAGAGAAACA X UUCAAC 20 GUACAUUACCUGGUA 279 GCGAGA AGAA GAAG 4743 CUUCG GCU 4837 ACCAGAGAAACA X UCUCGC GUACAUUACCUGGUA 310 UCCUCG AGAA GCAG 4744 CUGCA GCC 4838 25 ACCAGAGAAACA X CGAGGA GUACAUUACCUGGUA 325 AGCAAC AGAA GCUU 4745 AAGCG GCU 4839 ACCAGAGAAACA X GUUGCU GUACAUUACCUGGUA 30 328 ACGAGC AGAA GCCG 4746 CGGCU GUU 4840 ACCAGAGAAACA X GCUCGU GUACAUUACCUGGUA I I _ WO 99/50403 PCT/US99/06507 215 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 394 CAGCUG AGAA GCCC 4747 GGGCU GUA 4841 ACCAGAGAAACA X CAGCUG 5 GUACAUUACCUGGUA 399 UGUCGC AGAA GUAC 4748 GUACA GCU 4842 ACCAGAGAAACA X GCGACA GUACAUUACCUGGUA 413 CCCCCG AGAA GUGA 4749 UCACC GCC 4843 10 ACCAGAGAAACA X CGGGGG GUACAUUACCUGGUA 433 AACUCG AGAA GCGU 4750 ACGCG GAU 4844 ACCAGAGAAACA X CGAGUU GUACAUUACCUGGUA 15 455 CGUGGG AGAA GCAU 4751 AUGCU GAC 4845 ACCAGAGAAACA X CCCACG GUACAUUACCUGGUA 500 GCUCUG AGAA GUGA 4752 UCACC GUC 4846 ACCAGAGAAACA X CAGAGC 20 GUACAUUACCUGGUA 899 AGCAGG AGAA GGAA 4753 UUCCU GUU 4847 ACCAGAGAAACA X CCUGCU GUACAUUACCUGGUA 1162 UCAAAA AGAA GUGG 4754 CCACA GUA 4848 25 ACCAGAGAAACA X UUUUGA GUACAUUACCUGGUA 1224 UAUUCC AGAA GCCU 4755 AGGCA GAU 4849 ACCAGAGAAACA X GGAAUA GUACAUUACCUGGUA 30 1334 AGCUCC AGAA GCAA 4756 UUGCA GUU 4850 ACCAGAGAAACA X GGAGCU GUACAUUACCUGGUA I _I__ WO 99/50403 PCT/US99/06507 216 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 1345 UCAUCA AGAA GAGC 4757 GCUCC GUA 4851 ACCAGAGAAACA X UGAUGA 5 GUACAUUACCUGGUA 1490 AGCAAC AGAA GGGU 4758 ACCCU GAU 4852 ACCAGAGAAACA X GUUGCU GUACAUUACCUGGUA 1499 GGAACC AGAA GCAA 4759 UUGCU GUU 4853 10 ACCAGAGAAACA X GGUUCC GUACAUUACCUGGUA 1514 UACUGA AGAA GAGA 4760 UCUCA GAU 4854 ACCAGAGAAACA X UCAGUA GUACAUUACCUGGUA 15 1533 GCCGGG AGAA GAAA 4761 UUUCA GAU 4855 ACCAGAGAAACA X CCCGGC GUACAUUACCUGGUA 1540 AUCACA AGAA GGGA 4762 UCCCG GCC 4856 ACCAGAGAAACA X UGUGAU 20 GUACAUUACCUGGUA 1650 AUUCAA AGAA GGAU 4763 AUCCU GUU 4857 ACCAGAGAAACA X UUGAAU GUACAUUACCUGGUA 1673 AUAACC AGAA GGGU 4764 ACCCC GCU 4858 25 ACCAGAGAAACA X GGUUAU GUACAUUACCUGGUA 1759 UUUCGA AGAA GAAC 4765 GUUCA GUU 4859 ACCAGAGAAACA X UCGAAA GUACAUUACCUGGUA 30 1895 CACUGA AGAA GUUA 4766 UAACU GCC 4860 ACCAGAGAAACA X UCAGUG

GUACAUUACCUGGUA

WO 99/50403 PCTIUS99/06507 217 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 1973 GGGUUC AGAA GAAU 4767 AUUCA GAU 4861 ACCAGAGAAACA X GAACCC 5 GUACAUUACCUGGUA 1988 AAUAUG AGAA GUCU 4768 AGACA GCU 4862 ACCAGAGAAACA X CAUAUU GUACAUUACCUGGUA 2187 UGGAAG AGAA GUUU 4769 AAACA GCC 4863 10 ACCAGAGAAACA X CUUCCA GUACAUUACCUGGUA 2245 GUUGCA AGAA GUUU 4770 AAACU GAU 4864 ACCAGAGAAACA X UGCAAC GUACAUUACCUGGUA 15 2314 CAACUC AGAA GUUU 4771 AAACA GUU 4865 ACCAGAGAAACA X GAGUUG GUACAUUACCUGGUA 2351 CUCACA AGAA GCUU 4772 AAGCU GAC 4866 ACCAGAGAAACA X UGUGAG 20 GUACAUUACCUGGUA 2530 GAUAAA AGAA GUUC 4773 GAACU GCU 4867 ACCAGAGAAACA X UUUAUC GUACAUUACCUGGUA 2540 UCCCGA AGAA GAUA 4774 UAUCG GUC 4868 25 ACCAGAGAAACA X UCGGGA GUACAUUACCUGGUA 2585 GCCAAC AGAA GUAC 4775 GUACA GUU 4869 ACCAGAGAAACA X GUUGGC GUACAUUACCUGGUA 30 2917 UUAAGA AGAA GGUA 4776 UACCA GAC 4870 ACCAGAGAAACA X UCUUAA

GUACAUUACCUGGUA

WO 99/50403 PCT/US99/06507 218 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 2928 UCACGC AGAA GUUA 4777 UAACU GUA 4871 ACCAGAGAAACA X GCGUGA 5 GUACAUUACCUGGUA 2958 GCGGGC AGAA GAUG 4778 CAUCA GAU 4872 ACCAGAGAAACA X GCCCGC GUACAUUACCUGGUA 2965 CCCCGC AGAA GGCA 4779 UGCCC GCU 4873 10 ACCAGAGAAACA X GCGGGG GUACAUUACCUGGUA 3092 GGCAGC AGAA GUCA 4780 UGACU GCU 4874 ACCAGAGAAACA X GCUGCC GUACAUUACCUGGUA 15 3095 UUCGGC AGAA GCAG 4781 CUGCU GCU 4875 ACCAGAGAAACA X GCCGAA GUACAUUACCUGGUA 3098 AUUUUC AGAA GCAG 4782 CUGCU GCC 4876 ACCAGAGAAACA X GAAAAU 20 GUACAUUACCUGGUA 3164 CUGAGC AGAA GUCU 4783 AGACU GUA 4877 ACCAGAGAAACA X GCUCAG GUACAUUACCUGGUA 3172 CCCGAA AGAA GAGC 4784 GCUCA GUA 4878 25 ACCAGAGAAACA X UUCGGG GUACAUUACCUGGUA 3359 CUAUGC AGAA GAAG 4785 CUUCU GAU 4879 ACCAGAGAAACA X GCAUAG GUACAUUACCUGGUA 30 3581 UUUGGG AGAA GUGA 4786 UCACA GUA 4880 ACCAGAGAAACA X CCCAAA

GUACAUUACCUGGUA

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 4881 ACCAGAGAAACA X UUUUCC 5 IGUACAUUACCUGGUA 3633 GGAUUG AGAA GGCU 4788 AGCCU GCU 4882 ACCAGAGAAACA X CAAUCC GUACAUUACCUGGUA _ 3651 UCUGAA AGAA GUCC 4789 GGACU GAU 4883 10 ACCAGAGAAACA X UUCAGA GUACAUUACCUGGUA 3673 GGUUCG AGAA GUGU 4790 ACACA GUA 4884 ACCAGAGAAACA X CGAACC GUACAUUACCUGGUA 15 3686 AGUUAA AGAA GUAG 4791 CUACA GUU 4885 ACCAGAGAAACA X UUAACU GUACAUUACCUGGUA 3725 GUGCAA AGAA GGAG 4792 CUCCU GUU 4886 ACCAGAGAAACA X UUGCAC 20 GUACAUUACCUGGUA 3750 CAUUCC AGAA GUUU 4793 AAACU GUU 4887 ACCAGAGAAACA X GGAAUG GUACAUUACCUGGUA 3774 AAUUAC AGAA GUUA 4794 UAACU GCC 4888 25 ACCAGAGAAACA X GUAAUU GUACAUUACCUGGUA 3818 AUGUAA AGAA GCCA 4795 UGGCU GAC 4889 ACCAGAGAAACA X UUACAU GUACAUUACCUGGUA 30 3847 CAACUG AGAA GGCC 4796 GGCCU GCC 4890 ACCAGAGAAACA X CAGUUG GUACAUUACCUGGUA I WO 99/50403 PCT/US99/06507 220 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 3852 GAGUGC AGAA GGGC 4797 GCCCA GUU 4891 ACCAGAGAAACA X GCACUC 5 IGUACAUUACCUGGUA 3927 GGUUAG AGAA GCCA 4798 UGGCC GUC 4892 ACCAGAGAAACA X CUAACC GUACAUUACCUGGUA 3944 CUGCGC AGAA GGCC 4799 GGCCU GCU 4893 10 ACCAGAGAAACA X GCGCAG GUACAUUACCUGGUA 3952 AUGGAC AGAA GCGC 4800 GCGCA GAC 4894 ACCAGAGAAACA X GUCCAU GUACAUUACCUGGUA 15 3971 AUGUGG AGAA GCUA 4801 UAGCU GUC 4895 ACCAGAGAAACA X CCACAU GUACAUUACCUGGUA 4026 GUUUAA AGAA GCAC 4802 GUGCU GUC 4896 ACCAGAGAAACA X UUAAAC 20 GUACAUUACCUGGUA 4071 GGAAAA AGAA GUAG 4803 CUACC GUC 4897 ACCAGAGAAACA X UUUUCC GUACAUUACCUGGUA 4081 CUAGGA AGAA GGAA 4804 UUCCU GUU 4898 25 ACCAGAGAAACA X UCCUAG GUACAUUACCUGGUA 4104 GACGUG AGAA GGUA 4805 UACCU GCU 4899 ACCAGAGAAACA X CACGUC GUACAUUACCUGGUA 30 4165 AUUCAA AGAA GUUG 4806 CAACA GAC 4900 ACCAGAGAAACA X UUGAAU

GUACAUUACCUGGUA

WO 99/50403 PCT/US99/06507 221 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 4262 AGGGUA AGAA GGAG 4807 CUCCA GUU 4901 ACCAGAGAAACA X UACCCU 5 GUACAUUACCUGGUA 4426 GGUGGA AGAA GUCA 4808 UGACA GCC 4902 ACCAGAGAAACA X UCCACC GUACAUUACCUGGUA 4600 UGAGUA AGAA GCAC 4809 GUGCG GUU 4903 10 ACCAGAGAAACA X UACUCA GUACAUUACCUGGUA 4611 AUUUGC AGAA GUGA 4810 UCACU GCU 4904 ACCAGAGAAACA X GCAAAU GUACAUUACCUGGUA 15 4623 UGAAUA AGAA GUAU 4811 AUACU GUA 4905 ACCAGAGAAACA X UAUUCA GUACAUUACCUGGUA 4680 UACUGG AGAA GUUU 4812 AAACU GAU 4906 ACCAGAGAAACA X CCAGUA 20 GUACAUUACCUGGUA 4686 GUCUUA AGAA GGAU 4813 AUCCA GUA 4907 ACCAGAGAAACA X UAAGAC GUACAUUACCUGGUA 4769 UGGGAA AGAA GAUA 4814 UAUCU GUA 4908 25 ACCAGAGAAACA X UUCCCA GUACAUUACCUGGUA 4895 AAAAAA AGAA GCUU 4815 AAGCU GAU 4909 ACCAGAGAAACA X UUUUUU GUACAUUACCUGGUA 30 5015 ACUACA AGAA GUGU 4816 ACACA GUU 4910 ACCAGAGAAACA X UGUAGU

GUACAUUACCUGGUA

WO 99/50403 PCT/US99/06507 222 Seq. I.D. Seq. I.D. Position RZ No. Substrate No 5030 CAAAAC AGAA GUGG 4817 CCACU GUU 4911 ACCAGAGAAACA X GUUUUG 5 _GUACAUUACCUGGUA 5188 GCAAGA AGAA GAGA 4818 UCUCA GUU 4912 ACCAGAGAAACA X UCUUGC GUACAUUACCUGGUA 5259 CUAAAA AGAA GUCA 4819 UGACA GUU 4913 10 ACCAGAGAAACA X UUUUAG GUACAUUACCUGGUA 5399 AAUGCA AGAA GACC 4820 GGUCU GUU 4914 ACCAGAGAAACA X UGCAUU GUACAUUACCUGGUA 15 20 25 30 WO 99/50403 PCT/US99/06507 223 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 CGAA 4915 GAUGUGGUC 5702 ACCACAUC UUGCCCUC 5 19 UUGAGGGC CUGAUGAG X CGAA 4916 UGUGGUCUU 5703 AGACCACA GCCCUCAA 25 UACCUGUU CUGAUGAG X CGAA 4917 CUUGCCCUC 5704 AGGGCAAG AACAGGUA 33 AGACUACC CUGAUGAG X CGAA 4918 CAACAGGUA 5705 10 ACCUGUUG GGUAGUCU 37 CGGUAGAC CUGAUGAG X CGAA 4919 AGGUAGGUA 5706 ACCUACCU GUCUACCG 40 UUCCGGUA CUGAUGAG X CGAA 4920 UAGGUAGUC 5707 ACUACCUA UACCGGAA 15 42 UUUUCCGG CUGAUGAG X CGAA 4921 GGUAGUCUA 5708 AGACUACC CCGGAAAA 58 UCUUGCCU CUGAUGAG X CGAA 4922 ACCAAACUA 5709 AGUUUGGU AGGCAAGA 74 UAUUCACU CUGAUGAG X CGAA 4923 AAAAAAAUU 5710 20 AUUUUUUU AGUGAAUA 75 UUAUUCAC CUGAUGAG X CGAA 4924 AAAAAAUUA 5711 AAUUUUUU GUGAAUAA 82 UCCUUUAU CUGAUGAG X CGAA 4925 UAGUGAAUA 5712 AUUCACUA AUAAAGGA 25 85 CAGUCCUU CUGAUGAG X CGAA 4926 UGAAUAAUA 5713 AUUAUUCA AAGGACUG 101 CUUCUCUG CUGAUGAG X CGAA 4927 GAACCGGUU 5714 ACCGGUUC CAGAGAAG 102 CCUUCUCU CUGAUGAG X CGAA 4928 AACCGGUUC 5715 30 AACCGGUU AGAGAAGG 114 AUCUGCUG CUGAUGAG X CGAA 4929 GAAGGCAUU 5716 AUGCCUUC CAGCAGAU WO 99/50403 PCT/US99/06507 224 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 115 CAUCUGCU CUGAUGAG X CGAA 4930 AAGGCAUUC 5717 AAUGCCUU AGCAGAUG 5 125 GACUGGCA CUGAUGAG X CGAA 4931 GCAGAUGUU 5718 ACAUCUGC UGCCAGUC 126 UGACUGGC CUGAUGAG X CGAA 4932 CAGAUGUUU 5719 AACAUCUG GCCAGUCA 133 AUUCAUUU CUGAUGAG X CGAA 4933 UUGCCAGUC 5720 10 ACUGGCAA AAAUGAAU 142 CACACUUU CUGAUGAG X CGAA 4934 AAAUGAAUU 5721 AUUCAUUU AAAGUGUG 143 UCACACUU CUGAUGAG X CGAA 4935 AAUGAAUUA 5722 AAUUCAUU AAGUGUGA 15 164 ACUACCUC CUGAUGAG X CGAA 4936 AUGAAACUC 5723 AGUUUCAU GAGGUAGU 170 UCACCCAC CUGAUGAG X CGAA 4937 CUCGAGGUA 5724 ACCUCGAG GUGGGUGA 185 AUUCUUGG CUGAUGAG X CGAA 4938 GAAUGUGUC 5725 20 ACACAUUC CCAAGAAU 194 UUUCGCUG CUGAUGAG X CGAA 4939 CCAAGAAUC 5726 AUUCUUGG CAGCGAAA 209 UCCUGGGA CUGAUGAG X CGAA 4940 AACAGGGUC 5727 ACCCUGUU UCCCAGGA 25 211 CCUCCUGG CUGAUGAG X CGAA 4941 CAGGGUCUC 5728 AGACCCUG CCAGGAGG 235 CCUCUCCG CUGAUGAG X CGAA 4942 GGAAGGGUC 5729 ACCCUUCC CGGAGAGG 255 AAGGCCAG CUGAUGAG X CGAA 4943 CACAGGCUC 5730 30 AGCCUGUG CUGGCCUU 263 UGCUUAGA CUGAUGAG X CGAA 4944 CCUGGCCUU 5731 AGGCCAGG UCUAAGCA 264 GUGCUUAG CUGAUGAG X CGAA 4945 CUGGCCUUU 5732 AAGGCCAG CUAAGCAC WO 99/50403 PCTIUS99/06507 225 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 265 UGUGCUUA CUGAUGAG X CGAA 4946 UGGCCUUUC 5733 AAAGGCCA UAAGCACA 5 267 GGUGUGCU CUGAUGAG X CGAA 4947 GCCUUUCUA 5734 AGAAAGGC AGCACACC 287 GGGUCCGC CUGAUGAG X CGAA 4948 UGCCCAGUC 5735 ACUGGGCA GCGGACCC 337 CCCACGAG CUGAUGAG X CGAA 4949 AGGCGGGUC 5736 10 ACCCGCCU CUCGUGGG 340 UCGCCCAC CUGAUGAG X CGAA 4950 CGGGUCCUC 5737 AGGACCCG GUGGGCGA 378 UGGGAAAC CUGAUGAG X CGAA 4951 GGAGCAAUA 5738 AUUGCUCC GUUUCCCA 15 381 CGGUGGGA CUGAUGAG X CGAA 4952 GCAAUAGUU 5739 ACUAUUGC UCCCACCG 382 GCGGUGGG CUGAUGAG X CGAA 4953 CAAUAGUUU 5740 AACUAUUG CCCACCGC 383 AGCGGUGG CUGAUGAG X CGAA 4954 AAUAGUUUC 5741 20 AAACUAUU CCACCGCU 392 CUGAGAGG CUGAUGAG X CGAA 4955 CCACCGCUC 5742 AGCGGUGG CCUCUCAG 396 GCGCCUGA CUGAUGAG X CGAA 4956 CGCUCCCUC 5743 AGGGAGCG UCAGGCGC 25 398 CUGCGCCU CUGAUGAG X CGAA 4957 CUCCCUCUC 5744 AGAGGGAG AGGCGCAG 410 CUUCUCUA CUGAUGAG X CGAA 4958 CGCAGGGUC 5745 ACCCUGCG UAGAGAAG 412 CGCUUCUC CUGAUGAG X CGAA 4959 CAGGGUCUA 5746 30 AGACCCUG GAGAAGCG 430 CUUCUCUA CUGAUGAG X CGAA 4960 GAGGGGAUC 5747 AUCCCCUC UAGAGAAG 432 GGCUUCUC CUGAUGAG X CGAA 4961 GGGGAUCUA 5748 AGAUCCCC GAGAAGCC WO 99/50403 PCT/US99/06507 226 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 461 GGGCCGCG CUGAUGAG X CGAA 4962 GCGCGAGUC 5749 ACUCGCGC CGCGGCCC 5 477 UGGGACGC CUGAUGAG X CGAA 4963 CGCCCCGUU 5750 ACGGGGCG GCGUCCCA 482 GUGGGUGG CUGAUGAG X CGAA 4964 CGUUGCGUC 5751 ACGCAACG CCACCCAC 496 GGGGAGGG CUGAUGAG X CGAA 4965 CACCGCGUC 5752 10 ACGCGGUG CCCUCCCC 501 GGGGAGGG CUGAUGAG X CGAA 4966 CGUCCCCUC 5753 AGGGGACG CCCUCCCC 506 CGGGAGGG CUGAUGAG X CGAA 4967 CCUCCCCUC 5754 AGGGGAGG CCCUCCCG 15 511 CGCAGCGG CUGAUGAG X CGAA 4968 CCUCCCCUC 5755 AGGGGAGG CCGCUGCG 614 GUCGCCCA CUGAUGAG X CGAA 4969 CGGCCGCUC 5756 AGCGGCCG UGGGCGAC 653 CCUACGCC CUGAUGAG X CGAA 4970 GCGGGCGUU 5757 20 ACGCCCGC GGCGUAGG 659 UCACCUCC CUGAUGAG X CGAA 4971 GUUGGCGUA 5758 ACGCCAAC GGAGGUGA 676 CCGAGCCG CUGAUGAG X CGAA 4972 GUGAGGCUC 5759 AGCCUCAC CGGCUCGG 25 682 ACGCUGCC CUGAUGAG X CGAA 4973 CUCCGGCUC 5760 AGCCGGAG GGCAGCGU 691 GCAGCUGC CUGAUGAG X CGAA 4974 GGCAGCGUC 5761 ACGCUGCC GCAGCUGC 708 GGGGCGCA CUGAUGAG X CGAA 4975 CCCAGGAUC 5762 30 AUCCUGGG UGCGCCCC 720 CGCAACUU CUGAUGAG X CGAA 4976 GCCCCGGUC 5763 ACCGGGGC AAGUUGCG 725 AAGUCCGC CUGAUGAG X CGAA 4977 GGUCAAGUU 5764 ACUUGACC GCGGACUU WO 99/50403 PCT/US99/06507 227 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 733 CCGGCUCC CUGAUGAG X CGAA 4978 UGCGGACUU 5765 AGUCCGCA GGAGCCGG 5 760 GACGNGCG CUGAUGAG X CGAA 4979 GGACUGGUC 5766 ACCAGUCC CGCNCGUC 768 CCCACGCA CUGAUGAG X CGAA 4980 CCGCNCGUC 5767 ACGNGCGG UGCGUGGG 780 GACACGNG CUGAUGAG X CGAA 4981 GUGGGAAUN 5768 10 AUUCCCAC CNCGUGUC 788 CCAGCCAG CUGAUGAG X CGAA 4982 NCNCGUGUC 5769 ACACGNGN CUGGCUGG 803 CCGGNUCC CUGAUGAG X CGAA 4983 GGCNCGGUC 5770 ACCGNGCC GGANCCGG 15 825 GGGCCAGG CUGAUGAG X CGAA 4984 GGGNACCUU 5771 AGGUNCCC CCUGGCCC 826 CGGGCCAG CUGAUGAG X CGAA 4985 GGNACCUUC 5772 AAGGUNCC CUGGCCCG 877 UCUCGGAG CUGAUGAG X CGAA 4986 GAGCGGGUC 5773 20 ACCCGCUC CUCCGAGA 880 GCGUCUCG CUGAUGAG X CGAA 4987 CGGGUCCUC 5774 AGGACCCG CGAGACGC 898 GCCUGGCU CUGAUGAG X CGAA 4988 GAAGCCAUC 5775 AUGGCUUC AGCCAGGC 25 916 CGGCCGGG CUGAUGAG X CGAA 4989 GANNNCCUU 5776 AGGNNNUC CCCGGCCG 917 GCGGCCGG CUGAUGAG X CGAA 4990 ANNNCCUUC 5777 AAGGNNNU CCGGCCGC 954 GGCUCAGA CUGAUGAG X CGAA 4991 GGGCGCAUC 5778 30 AUGCGCCC UCUGAGCC 956 GGGGCUCA CUGAUGAG X CGAA 4992 GCGCAUCUC 5779 AGAUGCGC UGAGCCCC 970 CCCCGGGU CUGAUGAG X CGAA 4993 CCCGCGCUC 5780 AGCGCGGG ACCCGGGG WO 99/50403 PCT/US99/06507 228 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 989 NCACCCGC CUGAUGAG X CGAA 4994 GCGCGCGUC 5781 ACGCGCGC GCGGGUGN 5 999 CCGACCAG CUGAUGAG X CGAA 4995 CGGGUGNUC 5782 ANCACCCG CUGGUCGG 1005 CUUGGNCC CUGAUGAG X CGAA 4996 NUCCUGGUC 5783 ACCAGGAN GGNCCAAG 1048 ACCCCCGG CUGAUGAG X CGAA 4997 GUGGGGCUU 5784 10 AGCCCCAC CCGGGGGU 1049 AACCCCCG CUGAUGAG X CGAA 4998 UGGGGCUUC 5785 AAGCCCCA CGGGGGUU 1057 GCGGGAAC CUGAUGAG X CGAA 4999 CCGGGGGUU 5786 ACCCCCGG GUUCCCGC 15 1060 GGGGCGGG CUGAUGAG X CGAA 5000 GGGGUUGUU 5787 ACAACCCC CCCGCCCC 1061 AGGGGCGG CUGAUGAG X CGAA 5001 GGGUUGUUC 5788 AACAACCC CCGCCCCU 1070 CCUCUGCC CUGAUGAG X CGAA 5002 CCGCCCCUU 5789 20 AGGGGCGG GGCAGAGG 1089 CAGGAAGU CUGAUGAG X CGAA 5003 UGCCCUGUA 5790 ACAGGGCA ACUUCCUG 1093 CACCCAGG CUGAUGAG X CGAA 5004 CUGUAACUU 5791 AGUUACAG CCUGGGUG 25 1094 UCACCCAG CUGAUGAG X CGAA 5005 UGUAACUUC 5792 AAGUUACA CUGGGUGA 1123 GAAAUGUA CUGAUGAG X CGAA 5006 GCGCGGGUU 5793 ACCCGCGC UACAUUUC 1124 GGAAAUGU CUGAUGAG X CGAA 5007 CGCGGGUUU 5794 30 AACCCGCG ACAUUUCC 1125 GGGAAAUG CUGAUGAG X CGAA 5008 GCGGGUUUA 5795 AAACCCGC CAUUUCCC 1129 UGUGGGGA CUGAUGAG X CGAA 5009 GUUUACAUU 5796 AUGUAAAC UCCCCACA WO 99/50403 PCT/US99/06507 229 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1130 AUGUGGGG CUGAUGAG X CGAA 5010 UUUACAUUU 5797 AAUGUAAA CCCCACAU 5 1131 AAUGUGGG CUGAUGAG X CGAA 5011 UUACAUUUC 5798 AAAUGUAA CCCACAUU 1139 AAAUUGGA CUGAUGAG X CGAA 5012 CCCCACAUU 5799 AUGUGGGG UCCAAUUU 1140 GAAAUUGG CUGAUGAG X CGAA 5013 CCCACAUUU 5800 10 AAUGUGGG CCAAUUUC 1141 AGAAAUUG CUGAUGAG X CGAA 5014 CCACAUUUC 5801 AAAUGUGG CAAUUUCU 1146 ACAGGAGA CUGAUGAG X CGAA 5015 UUUCCAAUU 5802 AUUGGAAA UCUCCUGU 15 1147 AACAGGAG CUGAUGAG X CGAA 5016 UUCCAAUUU 5803 AAUUGGAA CUCCUGUU 1148 UAACAGGA CUGAUGAG X CGAA 5017 UCCAAUUUC 5804 AAAUUGGA UCCUGUUA 1150 CGUAACAG CUGAUGAG X CGAA 5018 CAAUUUCUC 5805 20 AGAAAUUG CUGUUACG 1155 GAAAGCGU CUGAUGAG X CGAA 5019 UCUCCUGUU 5806 ACAGGAGA ACGCUUUC 1156 AGAAAGCG CUGAUGAG X CGAA 5020 CUCCUGUUA 5807 AACAGGAG CGCUUUCU 25 1161 UCUGGAGA CUGAUGAG X CGAA 5021 GUUACGCUU 5808 AGCGUAAC UCUCCAGA 1162 UUCUGGAG CUGAUGAG X CGAA 5022 UUACGCUUU 5809 AAGCGUAA CUCCAGAA 1163 CUUCUGGA CUGAUGAG X CGAA 5023 UACGCUUUC 5810 30 AAAGCGUA UCCAGAAG 1165 ACCUUCUG CUGAUGAG X CGAA 5024 CGCUUUCUC 5811 AGAAAGCG CAGAAGGU 1174 AAAGAAAA CUGAUGAG X CGAA 5025 CAGAAGGUU 5812 ACCUUCUG UUUUCUUU WO 99/50403 PCT/US99/06507 230 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1175 GAAAGAAA CUGAUGAG X CGAA 5026 AGAAGGUUU 5813 AACCUUCU UUUCUUUC 5 1176 GGAAAGAA CUGAUGAG X CGAA 5027 GAAGGUUUU 5814 AAACCUUC UUCUUUCC 1177 AGGAAAGA CUGAUGAG X CGAA 5028 AAGGUUUUU 5815 AAAACCUU UCUUUCCU 1178 AAGGAAAG CUGAUGAG X CGAA 5029 AGGUUUUUU 5816 10 AAAAACCU CUUUCCUU 1179 AAAGGAAA CUGAUGAG X CGAA 5030 GGUUUUUUC 5817 AAAAAACC UUUCCUUU 1181 AAAAAGGA CUGAUGAG X CGAA 5031 UUUUUUCUU 5818 AGAAAAAA UCCUUUUU 15 1182 AAAAAAGG CUGAUGAG X CGAA 5032 UUUUUCUUU 5819 AAGAAAAA CCUUUUUU 1183 GAAAAAAG CUGAUGAG X CGAA 5033 UUUUCUUUC 5820 AAAGAAAA CUUUUUUC 1186 AAAGAAAA CUGAUGAG X CGAA 5034 UCUUUCCUU 5821 20 AGGAAAGA UUUUCUUU 1187 GAAAGAAA CUGAUGAG X CGAA 5035 CUUUCCUUU 5822 AAGGAAAG UUUCUUUC 1188 AGAAAGAA CUGAUGAG X CGAA 5036 UUUCCUUUU 5823 AAAGGAAA UUCUUUCU 25 1189 AAGAAAGA CUGAUGAG X CGAA 5037 UUCCUUUUU 5824 AAAAGGAA UCUUUCUU 1190 AAAGAAAG CUGAUGAG X CGAA 5038 UCCUUUUUU 5825 AAAAAGGA CUUUCUUU 1191 GAAAGAAA CUGAUGAG X CGAA 5039 CCUUUUUUC 5826 30 AAAAAAGG UUUCUUUC 1193 AAGAAAGA CUGAUGAG X CGAA 5040 UUUUUUCUU 5827 AGAAAAAA UCUUUCUU 1194 AAAGAAAG CUGAUGAG X CGAA 5041 UUUUUCUUU 5828 AAGAAAAA CUUUCUUU WO 99/50403 PCT/US99/06507 231 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1195 GAAAGAAA CUGAUGAG X CGAA 5042 UUUUCUUUC 5829 AAAGAAAA UUUCUUUC 5 1197 AAGAAAGA CUGAUGAG X CGAA 5043 UUCUUUCUU 5830 AGAAAGAA UCUUUCUU 1198 AAAGAAAG CUGAUGAG X CGAA 5044 UCUUUCUUU 5831 AAGAAAGA CUUUCUUU 1199 AAAAGAAA CUGAUGAG X CGAA 5045 CUUUCUUUC 5832 10 AAAGAAAG UUUCUUUU 1201 AAAAAAGA CUGAUGAG X CGAA 5046 UUCUUUCUU 5833 AGAAAGAA UCUUUUUU 1202 AAAAAAAG CUGAUGAG X CGAA 5047 UCUUUCUUU 5834 AAGAAAGA CUUUUUUU 15 1203 UAAAAAAA CUGAUGAG X CGAA 5048 CUUUCUUUC 5835 AAAGAAAG UUUUUUUA 1205 GGUAAAAA CUGAUGAG X CGAA 5049 UUCUUUCUU 5836 AGAAAGAA UUUUUACC 1206 AGGUAAAA CUGAUGAG X CGAA 5050 UCUUUCUUU 5837 20 AAGAAAGA UUUUACCU 1207 AAGGUAAA CUGAUGAG X CGAA 5051 CUUUCUUUU 5838 AAAGAAAG UUUACCUU 1208 GAAGGUAA CUGAUGAG X CGAA 5052 UUUCUUUUU 5839 AAAAGAAA UUACCUUC 25 1209 UGAAGGUA CUGAUGAG X CGAA 5053 UUCUUUUUU 5840 AAAAAGAA UACCUUCA 1210 UUGAAGGU CUGAUGAG X CGAA 5054 UCUUUUUUU 5841 AAAAAAGA ACCUUCAA 1211 GUUGAAGG CUGAUGAG X CGAA 5055 CUUUUUUUA 5842 30 AAAAAAAG CCUUCAAC 1215 GUAUGUUG CUGAUGAG X CGAA 5056 UUUUACCUU 5843 AGGUAAAA CAACAUAC 1216 AGUAUGUU CUGAUGAG X CGAA 5057 UUUACCUUC 5844 AAGGUAAA AACAUACU WO 99/50403 PCT/US99/06507 232 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1222 CGCAGGAG CUGAUGAG X CGAA 5058 UUCAACAUA 5845 AUGUUGAA CUCCUGCG 5 1225 CCCCGCAG CUGAUGAG X CGAA 5059 AACAUACUC 5846 AGUAUGUU CUGCGGGG 1235 UCCAAAAC CUGAUGAG X CGAA 5060 UGCGGGGUU 5847 ACCCCGCA GUUUUGGA 1238 UGCUCCAA CUGAUGAG X CGAA 5061 GGGGUUGUU 5848 10 ACAACCCC UUGGAGCA 1239 CUGCUCCA CUGAUGAG X CGAA 5062 GGGUUGUUU 5849 AACAACCC UGGAGCAG 1240 CCUGCUCC CUGAUGAG X CGAA 5063 GGUUGUUUU 5850 AAACAACC GGAGCAGG 15 1257 AGGAGGCA CUGAUGAG X CGAA 5064 AUGAGGCUU 5851 AGCCUCAU UGCCUCCU 1258 GAGGAGGC CUGAUGAG X CGAA 5065 UGAGGCUUU 5852 AAGCCUCA GCCUCCUC 1263 CACUGGAG CUGAUGAG X CGAA 5066 CUUUGCCUC 5853 20 AGGCAAAG CUCCAGUG 1266 GGACACUG CUGAUGAG X CGAA 5067 UGCCUCCUC 5854 AGGAGGCA CAGUGUCC 1273 CACCUGGG CUGAUGAG X CGAA 5068 UCCAGUGUC 5855 ACACUGGA CCCAGGUG 25 1294 UGGGAGCA CUGAUGAG X CGAA 5069 CGGUGCCUC 5856 AGGCACCG UGCUCCCA 1299 UGCCCUGG CUGAUGAG X CGAA 5070 CCUCUGCUC 5857 AGCAGAGG CCAGGGCA 1327 ACACUAGA CUGAUGAG X CGAA 5071 CGAAAAAUC 5858 30 AUUUUUCG UCUAGUGU 1329 AUACACUA CUGAUGAG X CGAA 5072 AAAAAUCUC 5859 AGAUUUUU UAGUGUAU 1331 GAAUACAC CUGAUGAG X CGAA 5073 AAAUCUCUA 5860 AGAGAUUU GUGUAUUC WO 99/50403 PCTIUS99/06507 233 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1336 UCCCCGAA CUGAUGAG X CGAA 5074 UCUAGUGUA 5861 ACACUAGA UUCGGGGA 5 1338 GUUCCCCG CUGAUGAG X CGAA 5075 UAGUGUAUU 5862 AUACACUA CGGGGAAC 1339 GGUUCCCC CUGAUGAG X CGAA 5076 AGUGUAUUC 5863 AAUACACU GGGGAACC 1359 GCCCAAGG CUGAUGAG X CGAA 5077 AAAAGGCUC 5864 10 AGCCUUUU CCUUGGGC 1363 ACCGGCCC CUGAUGAG X CGAA 5078 GGCUCCCUU 5865 AGGGAGCC GGGCCGGU 1377 AAGCCAAG CUGAUGAG X CGAA 5079 GGUGGGAUC 5866 AUCCCACC CUUGGCUU 15 1380 ACAAAGCC CUGAUGAG X CGAA 5080 GGGAUCCUU 5867 AGGAUCCC GGCUUUGU 1385 CAGAGACA CUGAUGAG X CGAA 5081 CCUUGGCUU 5868 AGCCAAGG UGUCUCUG 1386 CCAGAGAC CUGAUGAG X CGAA 5082 CUUGGCUUU 5869 20 AAGCCAAG GUCUCUGG 1389 CAGCCAGA CUGAUGAG X CGAA 5083 GGCUUUGUC 5870 ACAAAGCC UCUGGCUG 1391 AGCAGCCA CUGAUGAG X CGAA 5084 CUUUGUCUC 5871 AGACAAAG UGGCUGCU 25 1411 UGACGGCU CUGAUGAG X CGAA 5085 CACACCGUC 5872 ACGGUGUG AGCCGUCA 1418 AUUGCCCU CUGAUGAG X CGAA 5086 UCAGCCGUC 5873 ACGGCUGA AGGGCAAU 1427 CGAAUGCC CUGAUGAG X CGAA 5087 AGGGCAAUU 5874 30 AUUGCCCU GGCAUUCG 1433 AGAGGCCG CUGAUGAG X CGAA 5088 AUUGGCAUU 5875 AUGCCAAU CGGCCUCU 1434 AAGAGGCC CUGAUGAG X CGAA 5089 UUGGCAUUC 5876 AAUGCCAA GGCCUCUU WO 99/50403 PCT/US99/06507 234 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1440 GUACCAAA CUGAUGAG X CGAA 5090 UUCGGCCUC 5877 AGGCCGAA UUUGGUAC 5 1442 CAGUACCA CUGAUGAG X CGAA 5091 CGGCCUCUU 5878 AGAGGCCG UGGUACUG 1443 CCAGUACC CUGAUGAG X CGAA 5092 GGCCUCUUU 5879 AAGAGGCC GGUACUGG 1447 GUCCCCAG CUGAUGAG X CGAA 5093 UCUUUGGUA 5880 10 ACCAAAGA CUGGGGAC 1491 CGGGCAGC CUGAUGAG X CGAA 5094 CCCGGGGUU 5881 ACCCCGGG GCUGCCCG 1504 UCAGAGAG CUGAUGAG X CGAA 5095 CCCGUGGUC 5882 ACCACGGG CUCUCUGA 15 1507 GACUCAGA CUGAUGAG X CGAA 5096 GUGGUCCUC 5883 AGGACCAC UCUGAGUC 1509 AGGACUCA CUGAUGAG X CGAA 5097 GGUCCUCUC 5884 AGAGGACC UGAGUCCU 1515 UCACCAAG CUGAUGAG X CGAA 5098 CUCUGAGUC 5885 20 ACUCAGAG CUUGGUGA 1518 AAAUCACC CUGAUGAG X CGAA 5099 UGAGUCCUU 5886 AGGACUCA GGUGAUUU 1525 CCAGGCAA CUGAUGAG X CGAA 5100 UUGGUGAUU 5887 AUCACCAA UUGCCUGG 25 1526 CCCAGGCA CUGAUGAG X CGAA 5101 UGGUGAUUU 5888 AAUCACCA UGCCUGGG 1527 GCCCAGGC CUGAUGAG X CGAA 5102 GGUGAUUUU 5889 AAAUCACC GCCUGGGC 1554 CAGACCAG CUGAUGAG X CGAA 5103 CCCUGGCUC 5890 30 AGCCAGGG CUGGUCUG 1560 CCCCAGCA CUGAUGAG X CGAA 5104 CUCCUGGUC 5891 ACCAGGAG UGCUGGGG 1575 CUGAGGCA CUGAUGAG X CGAA 5105 GGCCGCCUC 5892 AGGCGGCC UGCCUCAG WO 99/50403 PCT/US99/06507 235 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1581 CAUCCUCU CUGAUGAG X CGAA 5106 CUCUGCCUC 5893 AGGCAGAG AGAGGAUG 5 1606 AAAAUACU CUGAUGAG X CGAA 5107 GUGCAUGUA 5894 ACAUGCAC AGUAUUUU 1610 AUUAAAAA CUGAUGAG X CGAA 5108 AUGUAAGUA 5895 ACUUACAU UUUUUAAU 1612 UUAUUAAA CUGAUGAG X CGAA 5109 GUAAGUAUU 5896 10 AUACUUAC UUUAAUAA 1613 UUUAUUAA CUGAUGAG X CGAA 5110 UAAGUAUUU 5897 AAUACUUA UUAAUAAA 1614 UUUUAUUA CUGAUGAG X CGAA 5111 AAGUAUUUU 5898 AAAUACUU UAAUAAAA 15 1615 UUUUUAUU CUGAUGAG X CGAA 5112 AGUAUUUUU 5899 AAAAUACU AAUAAAAA 1616 GUUUUUAU CUGAUGAG X CGAA 5113 GUAUUUUUA 5900 AAAAAUAC AUAAAAAC 1619 ACAGUUUU CUGAUGAG X CGAA 5114 UUUUUAAUA 5901 20 AUUAAAAA AAAACUGU 1628 ACGAGUAC CUGAUGAG X CGAA 5115 AAAACUGUA 5902 ACAGUUUU GUACUCGU 1631 UUUACGAG CUGAUGAG X CGAA 5116 ACUGUAGUA 5903 ACUACAGU CUCGUAAA 25 1634 UGUUUUAC CUGAUGAG X CGAA 5117 GUAGUACUC 5904 AGUACUAC GUAAAACA 1637 GAUUGUUU CUGAUGAG X CGAA 5118 GUACUCGUA 5905 ACGAGUAC AAACAAUC 1645 AGGGUGUA CUGAUGAG X CGAA 5119 AAAACAAUC 5906 30 AUUGUUUU UACACCCU 1647 GCAGGGUG CUGAUGAG X CGAA 5120 AACAAUCUA 5907 AGAUUGUU CACCCUGC 1665 AAAUAACA CUGAUGAG X CGAA 5121 GAAGGGAUU 5908 AUCCCUUC UGUUAUUU WO 99/50403 PCTIUS99/06507 236 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1666 AAAAUAAC CUGAUGAG X CGAA 5122 AAGGGAUUU 5909 AAUCCCUU GUUAUUUU 5 1669 AAUAAAAU CUGAUGAG X CGAA 5123 GGAUUUGUU 5910 ACAAAUCC AUUUUAUU 1670 AAAUAAAA CUGAUGAG X CGAA 5124 GAUUUGUUA 5911 AACAAAUC UUUUAUUU 1672 UAAAAUAA CUGAUGAG X CGAA 5125 UUUGUUAUU 5912 10 AUAACAAA UUAUUUUA 1673 AUAAAAUA CUGAUGAG X CGAA 5126 UUGUUAUUU 5913 AAUAACAA UAUUUUAU 1674 AAUAAAAU CUGAUGAG X CGAA 5127 UGUUAUUUU 5914 AAAUAACA AUUUUAUU 15 1675 UAAUAAAA CUGAUGAG X CGAA 5128 GUUAUUUUA 5915 AAAAUAAC UUUUAUUA 1677 AAUAAUAA CUGAUGAG X CGAA 5129 UAUUUUAUU 5916 AUAAAAUA UUAUUAUU 1678 AAAUAAUA CUGAUGAG X CGAA 5130 AUUUUAUUU 5917 20 AAUAAAAU UAUUAUUU 1679 UAAAUAAU CUGAUGAG X CGAA 5131 UUUUAUUUU 5918 AAAUAAAA AUUAUUUA 1680 AUAAAUAA CUGAUGAG X CGAA 5132 UUUAUUUUA 5919 AAAAUAAA UUAUUUAU 25 1682 AAAUAAAU CUGAUGAG X CGAA 5133 UAUUUUAUU 5920 AUAAAAUA AUUUAUUU 1683 UAAAUAAA CUGAUGAG X CGAA 5134 AUUUUAUUA 5921 AAUAAAAU UUUAUUUA 1685 AAUAAAUA CUGAUGAG X CGAA 5135 UUUAUUAUU 5922 30 AUAAUAAA UAUUUAUU 1686 AAAUAAAU CUGAUGAG X CGAA 5136 UUAUUAUUU 5923 AAUAAUAA AUUUAUUU 1687 UAAAUAAA CUGAUGAG X CGAA 5137 UAUUAUUUA 5924 AAAUAAUA UUUAUUUA WO 99/50403 PCT/US99/06507 237 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1689 AAUAAAUA CUGAUGAG X CGAA 5138 UUAUUUAUU 5925 AUAAAUAA UAUUUAUU 5 1690 AAAUAAAU CUGAUGAG X CGAA 5139 UAUUUAUUU 5926 AAUAAAUA AUUUAUUU 1691 UAAAUAAA CUGAUGAG X CGAA 5140 AUUUAUUUA 5927 AAAUAAAU UUUAUUUA 1693 AAUAAAUA CUGAUGAG X CGAA 5141 UUAUUUAUU 5928 10 AUAAAUAA UAUUUAUU 1694 AAAUAAAU CUGAUGAG X CGAA 5142 UAUUUAUUU 5929 AAUAAAUA AUUUAUUU 1695 UAAAUAAA CUGAUGAG X CGAA 5143 AUUUAUUUA 5930 AAAUAAAU UUUAUUUA 15 1697 AAUAAAUA CUGAUGAG X CGAA 5144 UUAUUUAUU 5931 AUAAAUAA UAUUUAUU 1698 AAAUAAAU CUGAUGAG X CGAA 5145 UAUUUAUUU 5932 AAUAAAUA AUUUAUUU 1699 AAAAUAAA CUGAUGAG X CGAA 5146 AUUUAUUUA 5933 20 AAAUAAAU UUUAUUUU 1701 CAAAAAUA CUGAUGAG X CGAA 5147 UUAUUUAUU 5934 AUAAAUAA UAUUUUUG 1702 UCAAAAAU CUGAUGAG X CGAA 5148 UAUUUAUUU 5935 AAUAAAUA AUUUUUGA 25 1703 CUCAAAAA CUGAUGAG X CGAA 5149 AUUUAUUUA 5936 AAAUAAAU UUUUUGAG 1705 GUCUCAAA CUGAUGAG X CGAA 5150 UUAUUUAUU 5937 AUAAAUAA UUUGAGAC 1706 CGUCUCAA CUGAUGAG X CGAA 5151 UAUUUAUUU 5938 30 AAUAAAUA UUGAGACG 1707 CCGUCUCA CUGAUGAG X CGAA 5152 AUUUAUUUU 5939 AAAUAAAU UGAGACGG 1708 UCCGUCUC CUGAUGAG X CGAA 5153 UUUAUUUUU 5940 AAAAUAAA GAGACGGA WO 99/50403 PCT/US99/06507 238 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1719 CAGAGCAA CUGAUGAG X CGAA 5154 GACGGAGUC 5941 ACUCCGUC UUGCUCUG 5 1721 GACAGAGC CUGAUGAG X CGAA 5155 CGGAGUCUU 5942 AGACUCCG GCUCUGUC 1725 GGGCGACA CUGAUGAG X CGAA 5156 GUCUUGCUC 5943 AGCAAGAC UGUCGCCC 1729 GCCUGGGC CUGAUGAG X CGAA 5157 UGCUCUGUC 5944 10 ACAGAGCA GCCCAGGC 1756 GAGCCGAG CUGAUGAG X CGAA 5158 UGGUGGGUU 5945 ACCCACCA CUCGGCUC 1757 UGAGCCGA CUGAUGAG X CGAA 5159 GGUGGGUUC 5946 AACCCACC UCGGCUCA 15 1759 AGUGAGCC CUGAUGAG X CGAA 5160 UGGGUUCUC 5947 AGAACCCA GGCUCACU 1764 GUUGCAGU CUGAUGAG X CGAA 5161 UCUCGGCUC 5948 AGCCGAGA ACUGCAAC 1774 GGAGGCAG CUGAUGAG X CGAA 5162 CUGCAACUU 5949 20 AGUUGCAG CUGCCUCC 1775 AGGAGGCA CUGAUGAG X CGAA 5163 UGCAACUUC 5950 AAGUUGCA UGCCUCCU 1781 AAACCCAG CUGAUGAG X CGAA 5164 UUCUGCCUC 5951 AGGCAGAA CUGGGUUU 25 1788 AUCGCUUA CUGAUGAG X CGAA 5165 UCCUGGGUU 5952 ACCCAGGA UAAGCGAU 1789 AAUCGCUU CUGAUGAG X CGAA 5166 CCUGGGUUU 5953 AACCCAGG AAGCGAUU 1790 GAAUCGCU CUGAUGAG X CGAA 5167 CUGGGUUUA 5954 30 AAACCCAG AGCGAUUC 1797 GCCAGAAG CUGAUGAG X CGAA 5168 UAAGCGAUU 5955 AUCGCUUA CUUCUGGC 1798 AGCCAGAA CUGAUGAG X CGAA 5169 AAGCGAUUC 5956 AAUCGCUU UUCUGGCU WO 99/50403 PCTIUS99/06507 239 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1800 UGAGCCAG CUGAUGAG X CGAA 5170 GCGAUUCUU 5957 AGAAUCGC CUGGCUCA 5 1801 CUGAGCCA CUGAUGAG X CGAA 5171 CGAUUCUUC 5958 AAGAAUCG UGGCUCAG 1807 GGGAGGCU CUGAUGAG X CGAA 5172 UUCUGGCUC 5959 AGCCAGAA AGCCUCCC 1813 CUACUCGG CUGAUGAG X CGAA 5173 CUCAGCCUC 5960 10 AGGCUGAG CCGAGUAG 1820 AUCCCAGC CUGAUGAG X CGAA 5174 UCCCGAGUA 5961 ACUCGGGA GCUGGGAU 1829 GCGCCUGU CUGAUGAG X CGAA 5175 GCUGGGAUU 5962 AUCCCAGC ACAGGCGC 15 1830 GGCGCCUG CUGAUGAG X CGAA 5176 CUGGGAUUA 5963 AAUCCCAG CAGGCGCC 1856 ACAAAAAU CUGAUGAG X CGAA 5177 GGCCGGCUA 5964 AGCCGGCC AUUUUUGU 1859 AAUACAAA CUGAUGAG X CGAA 5178 CGGCUAAUU 5965 20 AUUAGCCG UUUGUAUU 1860 AAAUACAA CUGAUGAG X CGAA 5179 GGCUAAUUU 5966 AAUUAGCC UUGUAUUU 1861 AAAAUACA CUGAUGAG X CGAA 5180 GCUAAUUUU 5967 AAAUUAGC UGUAUUUU 25 1862 AAAAAUAC CUGAUGAG X CGAA 5181 CUAAUUUUU 5968 AAAAUUAG GUAUUUUU 1865 ACUAAAAA CUGAUGAG X CGAA 5182 AUUUUUGUA 5969 ACAAAAAU UUUUUAGU 1867 CUACUAAA CUGAUGAG X CGAA 5183 UUUUGUAUU 5970 30 AUACAAAA UUUAGUAG 1868 UCUACUAA CUGAUGAG X CGAA 5184 UUUGUAUUU 5971 AAUACAAA UUAGUAGA 1869 CUCUACUA CUGAUGAG X CGAA 5185 UUGUAUUUU 5972 AAAUACAA UAGUAGAG WO 99/50403 PCTIUS99/06507 240 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1870 UCUCUACU CUGAUGAG X CGAA 5186 UGUAUUUUU 5973 AAAAUACA AGUAGAGA 5 1871 GUCUCUAC CUGAUGAG X CGAA 5187 GUAUUUUUA 5974 AAAAAUAC GUAGAGAC 1874 CGCGUCUC CUGAUGAG X CGAA 5188 UUUUUAGUA 5975 ACUAAAAA GAGACGCG 1885 CAUGGUGA CUGAUGAG X CGAA 5189 GACGCGGUU 5976 10 ACCGCGUC UCACCAUG 1886 ACAUGGUG CUGAUGAG X CGAA 5190 ACGCGGUUU 5977 AACCGCGU CACCAUGU 1887 AACAUGGU CUGAUGAG X CGAA 5191 CGCGGUUUC 5978 AAACCGCG ACCAUGUU 15 1895 GCCUGGCC CUGAUGAG X CGAA 5192 CACCAUGUU 5979 ACAUGGUG GGCCAGGC 1908 GAGCUCCA CUGAUGAG X CGAA 5193 AGGCUGGUC 5980 ACCAGCCU UGGAGCUC 1916 GAGGCCAG CUGAUGAG X CGAA 5194 CUGGAGCUC 5981 20 AGCUCCAG CUGGCCUC 1924 GAUCACUU CUGAUGAG X CGAA 5195 CCUGGCCUC 5982 AGGCCAGG AAGUGAUC 1932 GGUGGGCG CUGAUGAG X CGAA 5196 CAAGUGAUC 5983 AUCACUUG CGCCCACC 25 1942 GGGAGGCU CUGAUGAG X CGAA 5197 GCCCACCUC 5984 AGGUGGGC AGCCUCCC 1948 CACUUUGG CUGAUGAG X CGAA 5198 CUCAGCCUC 5985 AGGCUGAG CCAAAGUG 1965 CACGCCUG CUGAUGAG X CGAA 5199 CUGGGAAUA 5986 30 AUUCCCAG CAGGCGUG 1996 UUAAAAUA CUGAUGAG X CGAA 5200 GCCAGGAUU 5987 AUCCUGGC UAUUUUAA 1997 UUUAAAAU CUGAUGAG X CGAA 5201 CCAGGAUUU 5988 AAUCCUGG AUUUUAAA WO 99/50403 PCT/US99/06507 241 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 1998 UUUUAAAA CUGAUGAG X CGAA 5202 CAGGAUUUA 5989 AAAUCCUG UUUUAAAA 5 2000 CUUUUUAA CUGAUGAG X CGAA 5203 GGAUUUAUU 5990 AUAAAUCC UUAAAAAG 2001 CCUUUUUA CUGAUGAG X CGAA 5204 GAUUUAUUU 5991 AAUAAAUC UAAAAAGG 2002 CCCUUUUU CUGAUGAG X CGAA 5205 AUUUAUUUU 5992 10 AAAUAAAU AAAAAGGG 2003 UCCCUUUU CUGAUGAG X CGAA 5206 UUUAUUUUA 5993 AAAAUAAA AAAAGGGA 2016 UAUCAACA CUGAUGAG X CGAA 5207 GGGAAGAUU 5994 AUCUUCCC UGUUGAUA 15 2017 UUAUCAAC CUGAUGAG X CGAA 5208 GGAAGAUUU 5995 AAUCUUCC GUUGAUAA 2020 AAUUUAUC CUGAUGAG X CGAA 5209 AGAUUUGUU 5996 ACAAAUCU GAUAAAUU 2024 AGUGAAUU CUGAUGAG X CGAA 5210 UUGUUGAUA 5997 20 AUCAACAA AAUUCACU 2028 UUGAAGUG CUGAUGAG X CGAA 5211 UGAUAAAUU 5998 AUUUAUCA CACUUCAA 2029 UUUGAAGU CUGAUGAG X CGAA 5212 GAUAAAUUC 5999 AAUUUAUC ACUUCAAA 25 2033 UAUCUUUG CUGAUGAG X CGAA 5213 AAUUCACUU 6000 AGUGAAUU CAAAGAUA 2034 UUAUCUUU CUGAUGAG X CGAA 5214 AUUCACUUC 6001 AAGUGAAU AAAGAUAA 2041 GAAUAGUU CUGAUGAG X CGAA 5215 UCAAAGAUA 6002 30 AUCUUUGA AACUAUUC 2046 UUUUCGAA CUGAUGAG X CGAA 5216 GAUAAACUA 6003 AGUUUAUC UUCGAAAA 2048 UAUUUUCG CUGAUGAG X CGAA 5217 UAAACUAUU 6004 AUAGUUUA CGAAAAUA WO 99/50403 PCTIUS99/06507 242 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2049 GUAUUUUC CUGAUGAG X CGAA 5218 AAACUAUUC 6005 AAUAGUUU GAAAAUAC 5 2056 CACUAAAG CUGAUGAG X CGAA 5219 UCGAAAAUA 6006 AUUUUCGA CUUUAGUG 2059 AAUCACUA CUGAUGAG X CGAA 5220 AAAAUACUU 6007 AGUAUUUU UAGUGAUU 2060 GAAUCACU CUGAUGAG X CGAA 5221 AAAUACUUU 6008 10 AAGUAUUU AGUGAUUC 2061 GGAAUCAC CUGAUGAG X CGAA 5222 AAUACUUUA 6009 AAAGUAUU GUGAUUCC 2067 UUGACGGG CUGAUGAG X CGAA 5223 UUAGUGAUU 6010 AUCACUAA CCCGUCAA 15 2068 CUUGACGG CUGAUGAG X CGAA 5224 UAGUGAUUC 6011 AAUCACUA CCGUCAAG 2073 AGAGUCUU CUGAUGAG X CGAA 5225 AUUCCCGUC 6012 ACGGGAAU AAGACUCU 2080 ACACAGAA CUGAUGAG X CGAA 5226 UCAAGACUC 6013 20 AGUCUUGA UUCUGUGU 2082 AUACACAG CUGAUGAG X CGAA 5227 AAGACUCUU 6014 AGAGUCUU CUGUGUAU 2083 CAUACACA CUGAUGAG X CGAA 5228 AGACUCUUC 6015 AAGAGUCU UGUGUAUG 25 2089 UCUAUACA CUGAUGAG X CGAA 5229 UUCUGUGUA 6016 ACACAGAA UGUAUAGA 2093 UACGUCUA CUGAUGAG X CGAA 5230 GUGUAUGUA 6017 ACAUACAC UAGACGUA 2095 UAUACGUC CUGAUGAG X CGAA 5231 GUAUGUAUA 6018 30 AUACAUAC GACGUAUA 2101 AUGAGUUA CUGAUGAG X CGAA 5232 AUAGACGUA 6019 ACGUCUAU UAACUCAU 2103 GAAUGAGU CUGAUGAG X CGAA 5233 AGACGUAUA 6020 AUACGUCU ACUCAUUC WO 99/50403 PCTIUS99/06507 243 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2107 UCCAGAAU CUGAUGAG X CGAA 5234 GUAUAACUC 6021 AGUUAUAC AUUCUGGA 5 2110 CUGUCCAG CUGAUGAG X CGAA 5235 UAACUCAUU 6022 AUGAGUUA CUGGACAG 2111 CCUGUCCA CUGAUGAG X CGAA 5236 AACUCAUUC 6023 AAUGAGUU UGGACAGG 2128 AAAAAAGA CUGAUGAG X CGAA 5237 GCAAGGAUA 6024 10 AUCCUUGC UCUUUUUU 2130 CAAAAAAA CUGAUGAG X CGAA 5238 AAGGAUAUC 6025 AUAUCCUU UUUUUUUG 2132 AACAAAAA CUGAUGAG X CGAA 5239 GGAUAUCUU 6026 AGAUAUCC UUUUUGUU 15 2133 AAACAAAA CUGAUGAG X CGAA 5240 GAUAUCUUU 6027 AAGAUAUC UUUUGUUU 2134 CAAACAAA CUGAUGAG X CGAA 5241 AUAUCUUUU 6028 AAAGAUAU UUUGUUUG 2135 ACAAACAA CUGAUGAG X CGAA 5242 UAUCUUUUU 6029 20 AAAAGAUA UUGUUUGU 2136 AACAAACA CUGAUGAG X CGAA 5243 AUCUUUUUU 6030 AAAAAGAU UGUUUGUU 2137 AAACAAAC CUGAUGAG X CGAA 5244 UCUUUUUUU 6031 AAAAAAGA GUUUGUUU 25 2140 AACAAACA CUGAUGAG X CGAA 5245 UUUUUUGUU 6032 ACAAAAAA UGUUUGUU 2141 AAACAAAC CUGAUGAG X CGAA 5246 UUUUUGUUU 6033 AACAAAAA GUUUGUUU 2144 AACAAACA CUGAUGAG X CGAA 5247 UUGUUUGUU 6034 30 ACAAACAA UGUUUGUU 2145 AAACAAAC CUGAUGAG X CGAA 5248 UGUUUGUUU 6035 AACAAACA GUUUGUUU 2148 UCAAAACA CUGAUGAG X CGAA 5249 UUGUUUGUU 6036 ACAAACAA UGUUUUGA WO 99/50403 PCT/US99/06507 244 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2149 CUCAAAAC CUGAUGAG X CGAA 5250 UGUUUGUUU 6037 AACAAACA GUUUUGAG 5 2152 CAUCUCAA CUGAUGAG X CGAA 5251 UUGUUUGUU 6038 ACAAACAA UUGAGAUG 2153 CCAUCUCA CUGAUGAG X CGAA 5252 UGUUUGUUU 6039 AACAAACA UGAGAUGG 2154 UCCAUCUC CUGAUGAG X CGAA 5253 GUUUGUUUU 6040 10 AAACAAAC GAGAUGGA 2165 GACAGCGA CUGAUGAG X CGAA 5254 GAUGGACUC 6041 AGUCCAUC UCGCUGUC 2167 GCGACAGC CUGAUGAG X CGAA 5255 UGGACUCUC 6042 AGAGUCCA GCUGUCGC 15 2173 AGCCUGGC CUGAUGAG X CGAA 5256 CUCGCUGUC 6043 ACAGCGAG GCCAGGCU 2182 CUGCACUC CUGAUGAG X CGAA 5257 GCCAGGCUA 6044 AGCCUGGC GAGUGCAG 2200 UGAGCUGA CUGAUGAG X CGAA 5258 GGCGCGAUU 6045 20 AUCGCGCC UCAGCUCA 2201 GUGAGCUG CUGAUGAG X CGAA 5259 GCGCGAUUU 6046 AAUCGCGC CAGCUCAC 2202 AGUGAGCU CUGAUGAG X CGAA 5260 CGCGAUUUC 6047 AAAUCGCG AGCUCACU 25 2207 GUUGCAGU CUGAUGAG X CGAA 5261 UUUCAGCUC 6048 AGCUGAAA ACUGCAAC 2218 GGGAAGCG CUGAUGAG X CGAA 5262 UGCAACCUC 6049 AGGUUGCA CGCUUCCC 2223 AACCCGGG CUGAUGAG X CGAA 5263 CCUCCGCUU 6050 30 AGCGGAGG CCCGGGUU 2224 GAACCCGG CUGAUGAG X CGAA 5264 CUCCGCUUC 6051 AAGCGGAG CCGGGUUC 2231 AUCGCUUG CUGAUGAG X CGAA 5265 UCCCGGGUU 6052 ACCCGGGA CAAGCGAU WO 99/50403 PCTIUS99/06507 245 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2232 AAUCGCUU CUGAUGAG X CGAA 5266 CCCGGGUUC 6053 AACCCGGG AAGCGAUU 5 2240 GGCAGGAG CUGAUGAG X CGAA 5267 CAAGCGAUU 6054 AUCGCUUG CUCCUGCC 2241 AGGCAGGA CUGAUGAG X CGAA 5268 AAGCGAUUC 6055 AAUCGCUU UCCUGCCU 2243 UGAGGCAG CUGAUGAG X CGAA 5269 GCGAUUCUC 6056 10 AGAAUCGC CUGCCUCA 2250 GGGAGGCU CUGAUGAG X CGAA 5270 UCCUGCCUC 6057 AGGCAGGA AGCCUCCC 2256 CUACUCGG CUGAUGAG X CGAA 5271 CUCAGCCUC 6058 AGGCUGAG CCGAGUAG 15 2263 AUCCCAGC CUGAUGAG X CGAA 5272 UCCCGAGUA 6059 ACUCGGGA GCUGGGAU 2272 GUGCCUGU CUGAUGAG X CGAA 5273 GCUGGGAUU 6060 AUCCCAGC ACAGGCAC 2273 CGUGCCUG CUGAUGAG X CGAA 5274 CUGGGAUUA 6061 20 AAUCCCAG CAGGCACG 2296 AAAAUUAG CUGAUGAG X CGAA 5275 CACGCCCUA 6062 AGGGCGUG CUAAUUUU 2299 UCAAAAAU CUGAUGAG X CGAA 5276 GCCCUACUA 6063 AGUAGGGC AUUUUUGA 25 2302 AAAUCAAA CUGAUGAG X CGAA 5277 CUACUAAUU 6064 AUUAGUAG UUUGAUUU 2303 AAAAUCAA CUGAUGAG X CGAA 5278 UACUAAUUU 6065 AAUUAGUA UUGAUUUU 2304 AAAAAUCA CUGAUGAG X CGAA 5279 ACUAAUUUU 6066 30 AAAUUAGU UGAUUUUU 2305 UAAAAAUC CUGAUGAG X CGAA 5280 CUAAUUUUU 6067 AAAAUUAG GAUUUUUA 2309 CUACUAAA CUGAUGAG X CGAA 5281 UUUUUGAUU 6068 AUCAAAAA UUUAGUAG WO 99/50403 PCTIUS99/06507 246 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2310 UCUACUAA CUGAUGAG X CGAA 5282 UUUUGAUUU 6069 AAUCAAAA UUAGUAGA 5 2311 CUCUACUA CUGAUGAG X CGAA 5283 UUUGAUUUU 6070 AAAUCAAA UAGUAGAG 2312 UCUCUACU CUGAUGAG X CGAA 5284 UUGAUUUUU 6071 AAAAUCAA AGUAGAGA 2313 GUCUCUAC CUGAUGAG X CGAA 5285 UGAUUUUUA 6072 10 AAAAAUCA GUAGAGAC 2316 CCCGUCUC CUGAUGAG X CGAA 5286 UUUUUAGUA 6073 ACUAAAAA GAGACGGG 2327 CAUGGGGA CUGAUGAG X CGAA 5287 GACGGGAUU 6074 AUCCCGUC UCCCCAUG 15 2328 ACAUGGGG CUGAUGAG X CGAA 5288 ACGGGAUUU 6075 AAUCCCGU CCCCAUGU 2329 AACAUGGG CUGAUGAG X CGAA 5289 CGGGAUUUC 6076 AAAUCCCG CCCAUGUU 2337 UCCUGGCC CUGAUGAG X CGAA 5290 CCCCAUGUU 6077 20 ACAUGGGG GGCCAGGA 2350 GAGAUCGA CUGAUGAG X CGAA 5291 AGGAUGAUC 6078 AUCAUCCU UCGAUCUC 2352 AAGAGAUC CUGAUGAG X CGAA 5292 GAUGAUCUC 6079 AGAUCAUC GAUCUCUU 25 2356 GGUCAAGA CUGAUGAG X CGAA 5293 AUCUCGAUC 6080 AUCGAGAU UCUUGACC 2358 GGGGUCAA CUGAUGAG X CGAA 5294 CUCGAUCUC 6081 AGAUCGAG UUGACCCC 2360 ACGGGGUC CUGAUGAG X CGAA 5295 CGAUCUCUU 6082 30 AGAGAUCG GACCCCGU 2372 GGCAGGCU CUGAUGAG X CGAA 5296 CCCGUGAUC 6083 AUCACGGG AGCCUGCC 2382 GGGAGGCC CUGAUGAG X CGAA 5297 GCCUGCCUU 6084 AGGCAGGC GGCCUCCC WO 99/50403 PCT/US99/06507 247 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2388 CACUUUGG CUGAUGAG X CGAA 5298 CUUGGCCUC 6085 AGGCCAAG CCAAAGUG 5 2404 ACGCCUGU CUGAUGAG X CGAA 5299 GCUGGGAUU 6086 AUCCCAGC ACAGGCGU 2405 CACGCCUG CUGAUGAG X CGAA 5300 CUGGGAUUA 6087 AAUCCCAG CAGGCGUG 2437 CUUCAAGA CUGAUGAG X CGAA 5301 CCAAGGGUA 6088 10 ACCCUUGG UCUUGAAG 2439 UCCUUCAA CUGAUGAG X CGAA 5302 AAGGGUAUC 6089 AUACCCUU UUGAAGGA 2441 CCUCCUUC CUGAUGAG X CGAA 5303 GGGUAUCUU 6090 AGAUACCC GAAGGAGG 15 2453 UCAACUGU CUGAUGAG X CGAA 5304 GGAGGGAUU 6091 AUCCCUCC ACAGUUGA 2454 AUCAACUG CUGAUGAG X CGAA 5305 GAGGGAUUA 6092 AAUCCCUC CAGUUGAU 2459 UACAUAUC CUGAUGAG X CGAA 5306 AUUACAGUU 6093 20 ACUGUAAU GAUAUGUA 2463 CCUCUACA CUGAUGAG X CGAA 5307 CAGUUGAUA 6094 AUCAACUG UGUAGAGG 2467 UAUUCCUC CUGAUGAG X CGAA 5308 UGAUAUGUA 6095 ACAUAUCA GAGGAAUA 25 2475 CACUGCAA CUGAUGAG X CGAA 5309 AGAGGAAUA 6096 AUUCCUCU UUGCAGUG 2477 ACCACUGC CUGAUGAG X CGAA 5310 AGGAAUAUU 6097 AUAUUCCU GCAGUGGU 2486 GCAGCAAU CUGAUGAG X CGAA 5311 GCAGUGGUU 6098 30 ACCACUGC AUUGCUGC 2487 UGCAGCAA CUGAUGAG X CGAA 5312 CAGUGGUUA 6099 AACCACUG UUGCUGCA 2489 AAUGCAGC CUGAUGAG X CGAA 5313 GUGGUUAUU 6100 AUAACCAC GCUGCAUU WO 99/50403 PCT/US99/06507 248 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2497 ACAUAGGA CUGAUGAG X CGAA 5314 UGCUGCAUU 6101 AUGCAGCA UCCUAUGU 5 2498 CACAUAGG CUGAUGAG X CGAA 5315 GCUGCAUUU 6102 AAUGCAGC CCUAUGUG 2499 UCACAUAG CUGAUGAG X CGAA 5316 CUGCAUUUC 6103 AAAUGCAG CUAUGUGA 2502 CAGUCACA CUGAUGAG X CGAA 5317 CAUUUCCUA 6104 10 AGGAAAUG UGUGACUG 2516 AUCUGUUU CUGAUGAG X CGAA 5318 CUGGGACUA 6105 AGUCCCAG AAACAGAU 2525 UAUCAGCU CUGAUGAG X CGAA 5319 AAACAGAUC 6106 AUCUGUUU AGCUGAUA 15 2533 GCUAACAC CUGAUGAG X CGAA 5320 CAGCUGAUA 6107 AUCAGCUG GUGUUAGC 2538 UGCACGCU CUGAUGAG X CGAA 5321 GAUAGUGUU 6108 ACACUAUC AGCGUGCA 2539 CUGCACGC CUGAUGAG X CGAA 5322 AUAGUGUUA 6109 20 AACACUAU GCGUGCAG 2556 AGUCAUCA CUGAUGAG X CGAA 5323 UGAGCAGUC 6110 ACUGCUCA UGAUGACU 2565 CUGUGUCA CUGAUGAG X CGAA 5324 UGAUGACUA 6111 AGUCAUCA UGACACAG 25 2578 GAGAUUCU CUGAUGAG X CGAA 5325 ACAGAAAUA 6112 AUUUCUGU AGAAUCUC 2584 AUGCUGGA CUGAUGAG X CGAA 5326 AUAAGAAUC 6113 AUUCUUAU UCCAGCAU 2586 GAAUGCUG CUGAUGAG X CGAA 5327 AAGAAUCUC 6114 30 AGAUUCUU CAGCAUUC 2593 CAGGGCAG CUGAUGAG X CGAA 5328 UCCAGCAUU 6115 AUGCUGGA CUGCCCUG 2594 CCAGGGCA CUGAUGAG X CGAA 5329 CCAGCAUUC 6116 AAUGCUGG UGCCCUGG WO 99/50403 PCT/US99/06507 249 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2617 UCUGACCC CUGAUGAG X CGAA 5330 UGGAGCCUU 6117 AGGCUCCA GGGUCAGA 5 2622 CAGCAUCU CUGAUGAG X CGAA 5331 CCUUGGGUC 6118 ACCCAAGG AGAUGCUG 2637 GGCAUCAA CUGAUGAG X CGAA 5332 UGCUGGCUA 6119 AGCCAGCA UUGAUGCC 2639 CCGGCAUC CUGAUGAG X CGAA 5333 CUGGCUAUU 6120 10 AUAGCCAG GAUGCCGG 2660 CCCUGGUG CUGAUGAG X CGAA 5334 GGAGAAAUC 6121 AUUUCUCC CACCAGGG 2674 UUUUUACU CUGAUGAG X CGAA 5335 GGGCAACUC 6122 AGUUGCCC AGUAAAAA 15 2678 UUAUUUUU CUGAUGAG X CGAA 5336 AACUCAGUA 6123 ACUGAGUU AAAAAUAA 2685 UAUUUAUU CUGAUGAG X CGAA 5337 UAAAAAAUA 6124 AUUUUUUA AAUAAAUA 2689 UAUUUAUU CUGAUGAG X CGAA 5338 AAAUAAAUA 6125 20 AUUUAUUU AAUAAAUA 2693 UAUUUAUU CUGAUGAG X CGAA 5339 AAAUAAAUA 6126 AUUUAUUU AAUAAAUA 2697 UAUUUAUU CUGAUGAG X CGAA 5340 AAAUAAAUA 6127 AUUUAUUU AAUAAAUA 25 2701 UAUUUAUU CUGAUGAG X CGAA 5341 AAAUAAAUA 6128 AUUUAUUU AAUAAAUA 2705 UAUUUAUU CUGAUGAG X CGAA 5342 AAAUAAAUA 6129 AUUUAUUU AAUAAAUA 2709 UAAUUAUU CUGAUGAG X CGAA 5343 AAAUAAAUA 6130 30 AUUUAUUU AAUAAUUA 2713 UUUUUAAU CUGAUGAG X CGAA 5344 AAAUAAAUA 6131 AUUUAUUU AUUAAAAA 2716 CUUUUUUU CUGAUGAG X CGAA 5345 UAAAUAAUU 6132 AUUAUUUA AAAAAAAG WO 99/50403 PCT/US99/06507 250 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2717 CCUUUUUU CUGAUGAG X CGAA 5346 AAAUAAUUA 6133 AAUUAUUU AAAAAAGG 5 2728 GACAAGGA CUGAUGAG X CGAA 5347 AAAAGGGUA 6134 ACCCUUUU UCCUUGUC 2730 AGGACAAG CUGAUGAG X CGAA 5348 AAGGGUAUC 6135 AUACCCUU CUUGUCCU 2733 GACAGGAC CUGAUGAG X CGAA 5349 GGUAUCCUU 6136 10 AGGAUACC GUCCUGUC 2736 CUGGACAG CUGAUGAG X CGAA 5350 AUCCUUGUC 6137 ACAAGGAU CUGUCCAG 2741 UCAUCCUG CUGAUGAG X CGAA 5351 UGUCCUGUC 6138 ACAGGACA CAGGAUGA 15 2756 AUGGAAGC CUGAUGAG X CGAA 5352 GAGAUGCUU 6139 AGCAUCUC GCUUCCAU 2760 GUGCAUGG CUGAUGAG X CGAA 5353 UGCUUGCUU 6140 AGCAAGCA CCAUGCAC 2761 AGUGCAUG CUGAUGAG X CGAA 5354 GCUUGCUUC 6141 20 AAGCAAGC CAUGCACU 2770 AUUGUCGU CUGAUGAG X CGAA 5355 CAUGCACUU 6142 AGUGCAUG ACGACAAU 2771 AAUUGUCG CUGAUGAG X CGAA 5356 AUGCACUUA 6143 AAGUGCAU CGACAAUU 25 2779 ACAGCAAA CUGAUGAG X CGAA 5357 ACGACAAUU 6144 AUUGUCGU UUUGCUGU 2780 GACAGCAA CUGAUGAG X CGAA 5358 CGACAAUUU 6145 AAUUGUCG UUGCUGUC 2781 UGACAGCA CUGAUGAG X CGAA 5359 GACAAUUUU 6146 30 AAAUUGUC UGCUGUCA 2782 AUGACAGC CUGAUGAG X CGAA 5360 ACAAUUUUU 6147 AAAAUUGU GCUGUCAU 2788 UUUUUAAU CUGAUGAG X CGAA 5361 UUUGCUGUC 6148 ACAGCAAA AUUAAAAA WO 99/50403 PCT/US99/06507 251 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2791 AAUUUUUU CUGAUGAG X CGAA 5362 GCUGUCAUU 6149 AUGACAGC AAAAAAUU 5 2792 AAAUUUUU CUGAUGAG X CGAA 5363 CUGUCAUUA 6150 AAUGACAG AAAAAUUU 2799 AAUGUGAA CUGAUGAG X CGAA 5364 UAAAAAAUU 6151 AUUUUUUA UUCACAUU 2800 GAAUGUGA CUGAUGAG X CGAA 5365 AAAAAAUUU 6152 10 AAUUUUUU UCACAUUC 2801 UGAAUGUG CUGAUGAG X CGAA 5366 AAAAAUUUU 6153 AAAUUUUU CACAUUCA 2802 GUGAAUGU CUGAUGAG X CGAA 5367 AAAAUUUUC 6154 AAAAUUUU ACAUUCAC 15 2807 AGACUGUG CUGAUGAG X CGAA 5368 UUUCACAUU 6155 AUGUGAAA CACAGUCU 2808 AAGACUGU CUGAUGAG X CGAA 5369 UUCACAUUC 6156 AAUGUGAA ACAGUCUU 2814 AUUUAGAA CUGAUGAG X CGAA 5370 UUCACAGUC 6157 20 ACUGUGAA UUCUAAAU 2816 GAAUUUAG CUGAUGAG X CGAA 5371 CACAGUCUU 6158 AGACUGUG CUAAAUUC 2817 UGAAUUUA CUGAUGAG X CGAA 5372 ACAGUCUUC 6159 AAGACUGU UAAAUUCA 25 2819 AGUGAAUU CUGAUGAG X CGAA 5373 AGUCUUCUA 6160 AGAAGACU AAUUCACU 2823 CCAAAGUG CUGAUGAG X CGAA 5374 UUCUAAAUU 6161 AUUUAGAA CACUUUGG 2824 UCCAAAGU CUGAUGAG X CGAA 5375 UCUAAAUUC 6162 30 AAUUUAGA ACUUUGGA 2828 ACACUCCA CUGAUGAG X CGAA 5376 AAUUCACUU 6163 AGUGAAUU UGGAGUGU 2829 UACACUCC CUGAUGAG X CGAA 5377 AUUCACUUU 6164 AAGUGAAU GGAGUGUA WO 99/50403 PCT/US99/06507 252 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2837 GAAUCCAA CUGAUGAG X CGAA 5378 UGGAGUGUA 6165 ACACUCCA UUGGAUUC 5 2839 UGGAAUCC CUGAUGAG X CGAA 5379 GAGUGUAUU 6166 AUACACUC GGAUUCCA 2844 UGCAGUGG CUGAUGAG X CGAA 5380 UAUUGGAUU 6167 AUCCAAUA CCACUGCA 2845 AUGCAGUG CUGAUGAG X CGAA 5381 AUUGGAUUC 6168 10 AAUCCAAU CACUGCAU 2854 CGUAUGUC CUGAUGAG X CGAA 5382 CACUGCAUU 6169 AUGCAGUG GACAUACG 2860 AACUUACG CUGAUGAG X CGAA 5383 AUUGACAUA 6170 AUGUCAAU CGUAAGUU 15 2864 UGCAAACU CUGAUGAG X CGAA 5384 ACAUACGUA 6171 ACGUAUGU AGUUUGCA 2868 UUAAUGCA CUGAUGAG X CGAA 5385 ACGUAAGUU 6172 ACUUACGU UGCAUUAA 2869 UUUAAUGC CUGAUGAG X CGAA 5386 CGUAAGUUU 6173 20 AACUUACG GCAUUAAA 2874 GAUCUUUU CUGAUGAG X CGAA 5387 GUUUGCAUU 6174 AUGCAAAC AAAAGAUC 2875 GGAUCUUU CUGAUGAG X CGAA 5388 UUUGCAUUA 6175 AAUGCAAA AAAGAUCC 25 2882 UCUUAAAG CUGAUGAG X CGAA 5389 UAAAAGAUC 6176 AUCUUUUA CUUUAAGA 2885 AUAUCUUA CUGAUGAG X CGAA 5390 AAGAUCCUU 6177 AGGAUCUU UAAGAUAU 2886 GAUAUCUU CUGAUGAG X CGAA 5391 AGAUCCUUU 6178 30 AAGGAUCU AAGAUAUC 2887 AGAUAUCU CUGAUGAG X CGAA 5392 GAUCCUUUA 6179 AAAGGAUC AGAUAUCU 2892 UGACCAGA CUGAUGAG X CGAA 5393 UUUAAGAUA 6180 AUCUUAAA UCUGGUCA WO 99/50403 PCT/US99/06507 253 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 2894 CCUGACCA CUGAUGAG X CGAA 5394 UAAGAUAUC 6181 AUAUCUUA UGGUCAGG 5 2899 CCGUGCCU CUGAUGAG X CGAA 5395 UAUCUGGUC 6182 ACCAGAUA AGGCACGG 2913 ACAGGCGU CUGAUGAG X CGAA 5396 CGGUGGCUC 6183 AGCCACCG ACGCCUGU 2922 GCUGGGAU CUGAUGAG X CGAA 5397 ACGCCUGUA 6184 10 ACAGGCGU AUCCCAGC 2925 AGUGCUGG CUGAUGAG X CGAA 5398 CCUGUAAUC 6185 AUUACAGG CCAGCACU 2934 ACUUCCCA CUGAUGAG X CGAA 5399 CCAGCACUU 6186 AGUGCUGG UGGGAAGU 15 2935 CACUUCCC CUGAUGAG X CGAA 5400 CAGCACUUU 6187 AAGUGCUG GGGAAGUG 2949 AAUCCUUC CUGAUGAG X CGAA 5401 GUGGAGGUA 6188 ACCUCCAC GAAGGAUU 2957 GCUCAAGC CUGAUGAG X CGAA 5402 AGAAGGAUU 6189 20 AUCCUUCU GCUUGAGC 2961 CUGGGCUC CUGAUGAG X CGAA 5403 GGAUUGCUU 6190 AGCAAUCC GAGCCCAG 2974 UGGUCUCG CUGAUGAG X CGAA 5404 CCAGGAGUU 6191 ACUCCUGG CGAGACCA 25 2975 CUGGUCUC CUGAUGAG X CGAA 5405 CAGGAGUUC 6192 AACUCCUG GAGACCAG 2986 UGUUGCCC CUGAUGAG X CGAA 5406 GACCAGCUU 6193 AGCUGGUC GGGCAACA 2996 GGUCUCAC CUGAUGAG X CGAA 5407 GGCAACAUA 6194 30 AUGUUGCC GUGAGACC 3006 GUAGAGAU CUGAUGAG X CGAA 5408 UGAGACCUA 6195 AGGUCUCA AUCUCUAC 3009 UUAGUAGA CUGAUGAG X CGAA 5409 GACCUAAUC 6196 AUUAGGUC UCUACUAA WO 99/50403 PCT/US99/06507 254 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3011 UUUUAGUA CUGAUGAG X CGAA 5410 CCUAAUCUC 6197 AGAUUAGG UACUAAAA 5 3013 AUUUUUAG CUGAUGAG X CGAA 5411 UAAUCUCUA 6198 AGAGAUUA CUAAAAAU 3016 UUAAUUUU CUGAUGAG X CGAA 5412 UCUCUACUA 6199 AGUAGAGA AAAAUUAA 3022 UUUUUUUU CUGAUGAG X CGAA 5413 CUAAAAAUU 6200 10 AUUUUUAG AAAAAAAA 3023 UUUUUUUU CUGAUGAG X CGAA 5414 UAAAAAUUA 6201 AAUUUUUA AAAAAAAA 3033 CGCCUAAG CUGAUGAG X CGAA 5415 AAAAAAAUC 6202 AUUUUUUU CUUAGGCG 15 3036 GAUCGCCU CUGAUGAG X CGAA 5416 AAAAUCCUU 6203 AGGAUUUU AGGCGAUC 3037 AGAUCGCC CUGAUGAG X CGAA 5417 AAAUCCUUA 6204 AAGGAUUU GGCGAUCU 3044 UGUGAACA CUGAUGAG X CGAA 5418 UAGGCGAUC 6205 20 AUCGCCUA UGUUCACA 3048 AAUCUGUG CUGAUGAG X CGAA 5419 CGAUCUGUU 6206 ACAGAUCG CACAGAUU 3049 UAAUCUGU CUGAUGAG X CGAA 5420 GAUCUGUUC 6207 AACAGAUC ACAGAUUA 25 3056 ACAAGAUU CUGAUGAG X CGAA 5421 UCACAGAUU 6208 AUCUGUGA AAUCUUGU 3057 CACAAGAU CUGAUGAG X CGAA 5422 CACAGAUUA 6209 AAUCUGUG AUCUUGUG 3060 AAUCACAA CUGAUGAG X CGAA 5423 AGAUUAAUC 6210 30 AUUAAUCU UUGUGAUU 3062 CCAAUCAC CUGAUGAG X CGAA 5424 AUUAAUCUU 6211 AGAUUAAU GUGAUUGG 3068 AUCGCCCC CUGAUGAG X CGAA 5425 CUUGUGAUU 6212 AUCACAAG GGGGCGAU WO 99/50403 PCT/US99/06507 255 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3077 ACUUCUGG CUGAUGAG X CGAA 5426 GGGGCGAUU 6213 AUCGCCCC CCAGAAGU 5 3078 CACUUCUG CUGAUGAG X CGAA 5427 GGGCGAUUC 6214 AAUCGCCC CAGAAGUG 3096 CUCAGCAC CUGAUGAG X CGAA 5428 UGAUGGGUU 6215 ACCCAUCA GUGCUGAG 3107 UGUGGGGC CUGAUGAG X CGAA 5429 GCUGAGCUA 6216 10 AGCUCAGC GCCCCACA 3118 CUCAGAGA CUGAUGAG X CGAA 5430 CCCACACUC 6217 AGUGUGGG UCUCUGAG 3120 UUCUCAGA CUGAUGAG X CGAA 5431 CACACUCUC 6218 AGAGUGUG UCUGAGAA 15 3122 GCUUCUCA CUGAUGAG X CGAA 5432 CACUCUCUC 6219 AGAGAGUG UGAGAAGC 3136 CACUACUG CUGAUGAG X CGAA 5433 AGCAGUGUA 6220 ACACUGCU CAGUAGUG 3141 UUAAACAC CUGAUGAG X CGAA 5434 UGUACAGUA 6221 20 ACUGUACA GUGUUUAA 3146 UGCCCUUA CUGAUGAG X CGAA 5435 AGUAGUGUU 6222 ACACUACU UAAGGGCA 3147 CUGCCCUU CUGAUGAG X CGAA 5436 GUAGUGUUU 6223 AACACUAC AAGGGCAG 25 3148 CCUGCCCU CUGAUGAG X CGAA 5437 UAGUGUUUA 6224 AAACACUA AGGGCAGG 3161 UGACUUUA CUGAUGAG X CGAA 5438 CAGGGGCUC 6225 AGCCCCUG UAAAGUCA 3163 UCUGACUU CUGAUGAG X CGAA 5439 GGGGCUCUA 6226 30 AGAGCCCC AAGUCAGA 3168 GGAAGUCU CUGAUGAG X CGAA 5440 UCUAAAGUC 6227 ACUUUAGA AGACUUCC 3174 UACUCUGG CUGAUGAG X CGAA 5441 GUCAGACUU 6228 AGUCUGAC CCAGAGUA WO 99/50403 PCT/US99/06507 256 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3175 UUACUCUG CUGAUGAG X CGAA 5442 UCAGACUUC 6229 AAGUCUGA CAGAGUAA 5 3182 GGGGGUAU CUGAUGAG X CGAA 5443 UCCAGAGUA 6230 ACUCUGGA AUACCCCC 3185 GGGGGGGG CUGAUGAG X CGAA 5444 AGAGUAAUA 6231 AUUACUCU CCCCCCCC 3203 UGAUUUGU CUGAUGAG X CGAA 5445 CCCAACCUC 6232 10 AGGUUGGG ACAAAUCA 3210 UAGAAACU CUGAUGAG X CGAA 5446 UCACAAAUC 6233 AUUUGUGA AGUUUCUA 3214 AUAGUAGA CUGAUGAG X CGAA 5447 AAAUCAGUU 6234 ACUGAUUU UCUACUAU 15 3215 UAUAGUAG CUGAUGAG X CGAA 5448 AAUCAGUUU 6235 AACUGAUU CUACUAUA 3216 AUAUAGUA CUGAUGAG X CGAA 5449 AUCAGUUUC 6236 AAACUGAU UACUAUAU 3218 AAAUAUAG CUGAUGAG X CGAA 5450 CAGUUUCUA 6237 20 AGAAACUG CUAUAUUU 3221 UAUAAAUA CUGAUGAG X CGAA 5451 UUUCUACUA 6238 AGUAGAAA UAUUUAUA 3223 GAUAUAAA CUGAUGAG X CGAA 5452 UCUACUAUA 6239 AUAGUAGA UUUAUAUC 25 3225 CAGAUAUA CUGAUGAG X CGAA 5453 UACUAUAUU 6240 AUAUAGUA UAUAUCUG 3226 GCAGAUAU CUGAUGAG X CGAA 5454 ACUAUAUUU 6241 AAUAUAGU AUAUCUGC 3227 GGCAGAUA CUGAUGAG X CGAA 5455 CUAUAUUUA 6242 30 AAAUAUAG UAUCUGCC 3229 AUGGCAGA CUGAUGAG X CGAA 5456 AUAUUUAUA 6243 AUAAAUAU UCUGCCAU 3231 GGAUGGCA CUGAUGAG X CGAA 5457 AUUUAUAUC 6244 AUAUAAAU UGCCAUCC WO 99/50403 PCTIUS99/06507 257 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3238 AACACUGG CUGAUGAG X CGAA 5458 UCUGCCAUC 6245 AUGGCAGA CCAGUGUU 5 3246 CUACCACC CUGAUGAG X CGAA 5459 CCCAGUGUU 6246 ACACUGGG GGUGGUAG 3253 GAAGACCC CUGAUGAG X CGAA 5460 UUGGUGGUA 6247 ACCACCAA GGGUCUUC 3258 GAUCUGAA CUGAUGAG X CGAA 5461 GGUAGGGUC 6248 10 ACCCUACC UUCAGAUC 3260 GGGAUCUG CUGAUGAG X CGAA 5462 UAGGGUCUU 6249 AGACCCUA CAGAUCCC 3261 AGGGAUCU CUGAUGAG X CGAA 5463 AGGGUCUUC 6250 AAGACCCU AGAUCCCU 15 3266 UCCCCAGG CUGAUGAG X CGAA 5464 CUUCAGAUC 6251 AUCUGAAG CCUGGGGA 3296 AACUCUCC CUGAUGAG X CGAA 5465 AUGAGAGUA 6252 ACUCUCAU GGAGAGUU 3304 CCCAACAC CUGAUGAG X CGAA 5466 AGGAGAGUU 6253 20 ACUCUCCU GUGUUGGG 3309 GGAGUCCC CUGAUGAG X CGAA 5467 AGUUGUGUU 6254 ACACAACU GGGACUCC 3316 AACACUUG CUGAUGAG X CGAA 5468 UUGGGACUC 6255 AGUCCCAA CAAGUGUU 25 3324 GCCCCUUC CUGAUGAG X CGAA 5469 CCAAGUGUU 6256 ACACUUGG GAAGGGGC 3362 UCUGGGAC CUGAUGAG X CGAA 5470 AGAGAGGUU 6257 ACCUCUCU GUCCCAGA 3365 UACUCUGG CUGAUGAG X CGAA 5471 GAGGUUGUC 6258 30 ACAACCUC CCAGAGUA 3373 GACUCCGC CUGAUGAG X CGAA 5472 CCCAGAGUA 6259 ACUCUGGG GCGGAGUC 3381 CCAAAGCA CUGAUGAG X CGAA 5473 AGCGGAGUC 6260 ACUCCGCU UGCUUUGG WO 99/50403 PCT/US99/06507 258 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3386 UCUCCCCA CUGAUGAG X CGAA 5474 AGUCUGCUU 6261 AGCAGACU UGGGGAGA 5 3387 UUCUCCCC CUGAUGAG X CGAA 5475 GUCUGCUUU 6262 AAGCAGAC GGGGAGAA 3403 CCUCAGUC CUGAUGAG X CGAA 5476 AGAGAGAUU 6263 AUCUCUCU GACUGAGG 3414 CUUGAUGC CUGAUGAG X CGAA 5477 CUGAGGAUA 6264 10 AUCCUCAG GCAUCAAG 3419 AAAAACUU CUGAUGAG X CGAA 5478 GAUAGCAUC 6265 AUGCUAUC AAGUUUUU 3424 AAAUAAAA CUGAUGAG X CGAA 5479 CAUCAAGUU 6266 ACUUGAUG UUUUAUUU 15 3425 AAAAUAAA CUGAUGAG X CGAA 5480 AUCAAGUUU 6267 AACUUGAU UUUAUUUU 3426 UAAAAUAA CUGAUGAG X CGAA 5481 UCAAGUUUU 6268 AAACUUGA UUAUUUUA 3427 AUAAAAUA CUGAUGAG X CGAA 5482 CAAGUUUUU 6269 20 AAAACUUG UAUUUUAU 3428 CAUAAAAU CUGAUGAG X CGAA 5483 AAGUUUUUU 6270 AAAAACUU AUUUUAUG 3429 ACAUAAAA CUGAUGAG X CGAA 5484 AGUUUUUUA 6271 AAAAAACU UUUUAUGU 25 3431 GUACAUAA CUGAUGAG X CGAA 5485 UUUUUUAUU 6272 AUAAAAAA UUAUGUAC 3432 UGUACAUA CUGAUGAG X CGAA 5486 UUUUUAUUU 6273 AAUAAAAA UAUGUACA 3433 UUGUACAU CUGAUGAG X CGAA 5487 UUUUAUUUU 6274 30 AAAUAAAA AUGUACAA 3434 UUUGUACA CUGAUGAG X CGAA 5488 UUUAUUUUA 6275 AAAAUAAA UGUACAAA 3438 CAUCUUUG CUGAUGAG X CGAA 5489 UUUUAUGUA 6276 ACAUAAAA CAAAGAUG WO 99/50403 PCT/US99/06507 259 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3449 GCUAAAAA CUGAUGAG X CGAA 5490 AAGAUGAUC 6277 AUCAUCUU UUUUUAGC 5 3451 AAGCUAAA CUGAUGAG X CGAA 5491 GAUGAUCUU 6278 AGAUCAUC UUUAGCUU 3452 GAAGCUAA CUGAUGAG X CGAA 5492 AUGAUCUUU 6279 AAGAUCAU UUAGCUUC 3453 UGAAGCUA CUGAUGAG X CGAA 5493 UGAUCUUUU 6280 10 AAAGAUCA UAGCUUCA 3454 GUGAAGCU CUGAUGAG X CGAA 5494 GAUCUUUUU 6281 AAAAGAUC AGCUUCAC 3455 GGUGAAGC CUGAUGAG X CGAA 5495 AUCUUUUUA 6282 AAAAAGAU GCUUCACC 15 3459 CCUGGGUG CUGAUGAG X CGAA 5496 UUUUAGCUU 6283 AGCUAAAA CACCCAGG 3460 UCCUGGGU CUGAUGAG X CGAA 5497 UUUAGCUUC 6284 AAGCUAAA ACCCAGGA 3472 AAAACCCA CUGAUGAG X CGAA 5498 CAGGAAGUA 6285 20 ACUUCCUG UGGGUUUU 3478 AGACACAA CUGAUGAG X CGAA 5499 GUAUGGGUU 6286 ACCCAUAC UUGUGUCU 3479 AAGACACA CUGAUGAG X CGAA 5500 UAUGGGUUU 6287 AACCCAUA UGUGUCUU 25 3480 GAAGACAC CUGAUGAG X CGAA 5501 AUGGGUUUU 6288 AAACCCAU GUGUCUUC 3485 ACGAGGAA CUGAUGAG X CGAA 5502 UUUUGUGUC 6289 ACACAAAA UUCCUCGU 3487 ACACGAGG CUGAUGAG X CGAA 5503 UUGUGUCUU 6290 30 AGACACAA CCUCGUGU 3488 AACACGAG CUGAUGAG X CGAA 5504 UGUGUCUUC 6291 AAGACACA CUCGUGUU 3491 CUAAACAC CUGAUGAG X CGAA 5505 GUCUUCCUC 6292 AGGAAGAC GUGUUUAG WO 99/50403 PCT/US99/06507 260 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3496 AAAACCUA CUGAUGAG X CGAA 5506 CCUCGUGUU 6293 ACACGAGG UAGGUUUU 5 3497 AAAAACCU CUGAUGAG X CGAA 5507 CUCGUGUUU 6294 AACACGAG AGGUUUUU 3498 UAAAAACC CUGAUGAG X CGAA 5508 UCGUGUUUA 6295 AAACACGA GGUUUUUA 3502 AGAAUAAA CUGAUGAG X CGAA 5509 GUUUAGGUU 6296 10 ACCUAAAC UUUAUUCU 3503 CAGAAUAA CUGAUGAG X CGAA 5510 UUUAGGUUU 6297 AACCUAAA UUAUUCUG 3504 UCAGAAUA CUGAUGAG X CGAA 5511 UUAGGUUUU 6298 AAACCUAA UAUUCUGA 15 3505 GUCAGAAU CUGAUGAG X CGAA 5512 UAGGUUUUU 6299 AAAACCUA AUUCUGAC 3506 GGUCAGAA CUGAUGAG X CGAA 5513 AGGUUUUUA 6300 AAAAACCU UUCUGACC 3508 UAGGUCAG CUGAUGAG X CGAA 5514 GUUUUUAUU 6301 20 AUAAAAAC CUGACCUA 3509 UUAGGUCA CUGAUGAG X CGAA 5515 UUUUUAUUC 6302 AAUAAAAA UGACCUAA 3516 GACCUAAU CUGAUGAG X CGAA 5516 UCUGACCUA 6303 AGGUCAGA AUUAGGUC 25 3519 UUAGACCU CUGAUGAG X CGAA 5517 GACCUAAUU 6304 AUUAGGUC AGGUCUAA 3520 CUUAGACC CUGAUGAG X CGAA 5518 ACCUAAUUA 6305 AAUUAGGU GGUCUAAG 3524 UCAGCUUA CUGAUGAG X CGAA 5519 AAUUAGGUC 6306 30 ACCUAAUU UAAGCUGA 3526 CCUCAGCU CUGAUGAG X CGAA 5520 UUAGGUCUA 6307 AGACCUAA AGCUGAGG 3539 AGAGAAAU CUGAUGAG X CGAA 5521 GAGGUGCUU 6308 AGCACCUC AUUUCUCU WO 99/50403 PCTIUS99/06507 261 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3540 AAGAGAAA CUGAUGAG X CGAA 5522 AGGUGCUUA 6309 AAGCACCU UUUCUCUU 5 3542 AGAAGAGA CUGAUGAG X CGAA 5523 GUGCUUAUU 6310 AUAAGCAC UCUCUUCU 3543 CAGAAGAG' CUGAUGAG X CGAA 5524 UGCUUAUUU 6311 AAUAAGCA CUCUUCUG 3544 CCAGAAGA CUGAUGAG X CGAA 5525 GCUUAUUUC 6312 10 AAAUAAGC UCUUCUGG 3546 CUCCAGAA CUGAUGAG X CGAA 5526 UUAUUUCUC 6313 AGAAAUAA UUCUGGAG 3548 AACUCCAG CUGAUGAG X CGAA 5527 AUUUCUCUU 6314 AGAGAAAU CUGGAGUU 15 3549 AAACUCCA CUGAUGAG X CGAA 5528 UUUCUCUUC 6315 AAGAGAAA UGGAGUUU 3556 AGGAUAUA CUGAUGAG X CGAA 5529 UCUGGAGUU 6316 ACUCCAGA UAUAUCCU 3557 UAGGAUAU CUGAUGAG X CGAA 5530 CUGGAGUUU 6317 20 AACUCCAG AUAUCCUA 3558 CUAGGAUA CUGAUGAG X CGAA 5531 UGGAGUUUA 6318 AAACUCCA UAUCCUAG 3560 UUCUAGGA CUGAUGAG X CGAA 5532 GAGUUUAUA 6319 AUAAACUC UCCUAGAA 25 3562 GCUUCUAG CUGAUGAG X CGAA 5533 GUUUAUAUC 6320 AUAUAAAC CUAGAAGC 3565 AGAGCUUC CUGAUGAG X CGAA 5534 UAUAUCCUA 6321 AGGAUAUA GAAGCUCU 3572 CGAUUGGA CUGAUGAG X CGAA 5535 UAGAAGCUC 6322 30 AGCUUCUA UCCAAUCG 3574 UUCGAUUG CUGAUGAG X CGAA 5536 GAAGCUCUC 6323 AGAGCUUC CAAUCGAA 3579 AGGGCUUC CUGAUGAG X CGAA 5537 UCUCCAAUC 6324 AUUGGAGA GAAGCCCU WO 99/50403 PCT/US99/06507 262 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3588 UACCUGCA CUGAUGAG X CGAA 5538 GAAGCCCUC 6325 AGGGCUUC UGCAGGUA 5 3596 CCUGAGGA CUGAUGAG X CGAA 5539 CUGCAGGUA 6326 ACCUGCAG UCCUCAGG 3598 GACCUGAG CUGAUGAG X CGAA 5540 GCAGGUAUC 6327 AUACCUGC CUCAGGUC 3601 CAGGACCU CUGAUGAG X CGAA 5541 GGUAUCCUC 6328 10 AGGAUACC AGGUCCUG 3606 UUCUCCAG CUGAUGAG X CGAA 5542 CCUCAGGUC 6329 ACCUGAGG CUGGAGAA 3631 AAGCCAAC CUGAUGAG X CGAA 5543 GGAAGGCUU 6330 AGCCUUCC GUUGGCUU 15 3634 CCGAAGCC CUGAUGAG X CGAA 5544 AGGCUUGUU 6331 ACAAGCCU GGCUUCGG 3639 CCUUUCCG CUGAUGAG X CGAA 5545 UGUUGGCUU 6332 AGCCAACA CGGAAAGG 3640 CCCUUUCC CUGAUGAG X CGAA 5546 GUUGGCUUC 6333 20 AAGCCAAC GGAAAGGG 3655 UUAAACCA CUGAUGAG X CGAA 5547 GGAGGGCUA 6334 AGCCCUCC UGGUUUAA 3660 UGGCUUUA CUGAUGAG X CGAA 5548 GCUAUGGUU 6335 ACCAUAGC UAAAGCCA 25 3661 CUGGCUUU CUGAUGAG X CGAA 5549 CUAUGGUUU 6336 AACCAUAG AAAGCCAG 3662 ACUGGCUU CUGAUGAG X CGAA 5550 UAUGGUUUA 6337 AAACCAUA AAGCCAGU 3671 CCACAUCU CUGAUGAG X CGAA 5551 AAGCCAGUA 6338 30 ACUGGCUU AGAUGUGG 3682 AAGAAUCA CUGAUGAG X CGAA 5552 AUGUGGGUU 6339 ACCCACAU UGAUUCUU 3683 CAAGAAUC CUGAUGAG X CGAA 5553 UGUGGGUUU 6340 AACCCACA GAUUCUUG WO 99/50403 PCT/US99/06507 263 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3687 AAGUCAAG CUGAUGAG X CGAA 5554 GGUUUGAUU 6341 AUCAAACC CUUGACUU 5 3688 AAAGUCAA CUGAUGAG X CGAA 5555 GUUUGAUUC 6342 AAUCAAAC UUGACUUU 3690 ACAAAGUC CUGAUGAG X CGAA 5556 UUGAUUCUU 6343 AGAAUCAA GACUUUGU 3695 AGGAGACA CUGAUGAG X CGAA 5557 UCUUGACUU 6344 10 AGUCAAGA UGUCUCCU 3696 CAGGAGAC CUGAUGAG X CGAA 5558 CUUGACUUU 6345 AAGUCAAG GUCUCCUG 3699 CUACAGGA CUGAUGAG X CGAA 5559 GACUUUGUC 6346 ACAAAGUC UCCUGUAG 15 3701 GCCUACAG CUGAUGAG X CGAA 5560 CUUUGUCUC 6347 AGACAAAG CUGUAGGC 3706 ACACAGCC CUGAUGAG X CGAA 5561 UCUCCUGUA 6348 ACAGGAGA GGCUGUGU 3720 ACUUAUUU CUGAUGAG X CGAA 5562 UGUGGCCUU 6349 20 AGGCCACA AAAUAAGU 3721 AACUUAUU CUGAUGAG X CGAA 5563 GUGGCCUUA 6350 AAGGCCAC AAUAAGUU 3725 AGGUAACU CUGAUGAG X CGAA 5564 CCUUAAAUA 6351 AUUUAAGG AGUUACCU 25 3729 GAUUAGGU CUGAUGAG X CGAA 5565 AAAUAAGUU 6352 ACUUAUUU ACCUAAUC 3730 AGAUUAGG CUGAUGAG X CGAA 5566 AAUAAGUUA 6353 AACUUAUU CCUAAUCU 3734 CAAGAGAU CUGAUGAG X CGAA 5567 AGUUACCUA 6354 30 AGGUAACU AUCUCUUG 3737 ACUCAAGA CUGAUGAG X CGAA 5568 UACCUAAUC 6355 AUUAGGUA UCUUGAGU 3739 GGACUCAA CUGAUGAG X CGAA 5569 CCUAAUCUC 6356 AGAUUAGG UUGAGUCC WO 99/50403 PCT/US99/06507 264 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3741 GAGGACUC CUGAUGAG X CGAA 5570 UAAUCUCUU 6357 AGAGAUUA GAGUCCUC 5 3746 AAACUGAG CUGAUGAG X CGAA 5571 UCUUGAGUC 6358 ACUCAAGA CUCAGUUU 3749 AGGAAACU CUGAUGAG X CGAA 5572 UGAGUCCUC 6359 AGGACUCA AGUUUCCU 3753 AAUGAGGA CUGAUGAG X CGAA 5573 UCCUCAGUU 6360 10 ACUGAGGA UCCUCAUU 3754 AAAUGAGG CUGAUGAG X CGAA 5574 CCUCAGUUU 6361 AACUGAGG CCUCAUUU 3755 CAAAUGAG CUGAUGAG X CGAA 5575 CUCAGUUUC 6362 AAACUGAG CUCAUUUG 15 3758 UUACAAAU CUGAUGAG X CGAA 5576 AGUUUCCUC 6363 AGGAAACU AUUUGUAA 3761 GCCUUACA CUGAUGAG X CGAA 5577 UUCCUCAUU 6364 AUGAGGAA UGUAAGGC 3762 UGCCUUAC CUGAUGAG X CGAA 5578 UCCUCAUUU 6365 20 AAUGAGGA GUAAGGCA 3765 CUCUGCCU CUGAUGAG X CGAA 5579 UCAUUUGUA 6366 ACAAAUGA AGGCAGAG 3786 CAUAAUCA CUGAUGAG X CGAA 5580 CAAUGCCUA 6367 AGGCAUUG UGAUUAUG 25 3791 AUCAGCAU CUGAUGAG X CGAA 5581 CCUAUGAUU 6368 AUCAUAGG AUGCUGAU 3792 AAUCAGCA CUGAUGAG X CGAA 5582 CUAUGAUUA 6369 AAUCAUAG UGCUGAUU 3800 UUUCAUUU CUGAUGAG X CGAA 5583 AUGCUGAUU 6370 30 AUCAGCAU AAAUGAAA 3801 GUUUCAUU CUGAUGAG X CGAA 5584 UGCUGAUUA 6371 AAUCAGCA AAUGAAAC 3823 UAAACACU CUGAUGAG X CGAA 5585 CACAAAAUA 6372 AUUUUGUG AGUGUUUA WO 99/50403 PCT/US99/06507 265 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3829 AUUCAUUA CUGAUGAG X CGAA 5586 AUAAGUGUU 6373 ACACUUAU UAAUGAAU 5 3830 CAUUCAUU CUGAUGAG X CGAA 5587 UAAGUGUUU 6374 AACACUUA AAUGAAUG 3831 UCAUUCAU CUGAUGAG X CGAA 5588 AAGUGUUUA 6375 AAACACUU AUGAAUGA 3845 GACAAUAG CUGAUGAG X CGAA 5589 UGACAACUA 6376 10 AGUUGUCA CUAUUGUC 3848 AAUGACAA CUGAUGAG X CGAA 5590 CAACUACUA 6377 AGUAGUUG UUGUCAUU 3850 AUAAUGAC CUGAUGAG X CGAA 5591 ACUACUAUU 6378 AUAGUAGU GUCAUUAU 15 3853 AGAAUAAU CUGAUGAG X CGAA 5592 ACUAUUGUC 6379 ACAAUAGU AUUAUUCU 3856 GGAAGAAU CUGAUGAG X CGAA 5593 AUUGUCAUU 6380 AUGACAAU AUUCUUCC 3857 AGGAAGAA CUGAUGAG X CGAA 5594 UUGUCAUUA 6381 20 AAUGACAA UUCUUCCU 3859 AUAGGAAG CUGAUGAG X CGAA 5595 GUCAUUAUU 6382 AUAAUGAC CUUCCUAU 3860 GAUAGGAA CUGAUGAG X CGAA 5596 UCAUUAUUC 6383 AAUAAUGA UUCCUAUC 25 3862 UGGAUAGG CUGAUGAG X CGAA 5597 AUUAUUCUU 6384 AGAAUAAU CCUAUCCA 3863 AUGGAUAG CUGAUGAG X CGAA 5598 UUAUUCUUC 6385 AAGAAUAA CUAUCCAU 3866 AGCAUGGA CUGAUGAG X CGAA 5599 UUCUUCCUA 6386 30 AGGAAGAA UCCAUGCU 3868 AUAGCAUG CUGAUGAG X CGAA 5600 CUUCCUAUC 6387 AUAGGAAG CAUGCUAU 3875 AUGGCAGA CUGAUGAG X CGAA 5601 UCCAUGCUA 6388 AGCAUGGA UCUGCCAU WO 99/50403 PCT/US99/06507 266 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3877 ACAUGGCA CUGAUGAG X CGAA 5602 CAUGCUAUC 6389 AUAGCAUG UGCCAUGU 5 3886 GCCUCCAA CUGAUGAG X CGAA 5603 UGCCAUGUA 6390 ACAUGGCA UUGGAGGC 3888 UUGCCUCC CUGAUGAG X CGAA 5604 CCAUGUAUU 6391 AUACAUGG GGAGGCAA 3904 GAAGUAGU CUGAUGAG X CGAA 5605 AAAGCUGUU 6392 10 ACAGCUUU ACUACUUC 3905 UGAAGUAG CUGAUGAG X CGAA 5606 AAGCUGUUA 6393 AACAGCUU CUACUUCA 3908 GCAUGAAG CUGAUGAG X CGAA 5607 CUGUUACUA 6394 AGUAACAG CUUCAUGC 15 3911 UAUGCAUG CUGAUGAG X CGAA 5608 UUACUACUU 6395 AGUAGUAA CAUGCAUA 3912 AUAUGCAU CUGAUGAG X CGAA 5609 UACUACUUC 6396 AAGUAGUA AUGCAUAU 3919 AUAGCGCA CUGAUGAG X CGAA 5610 UCAUGCAUA 6397 20 AUGCAUGA UGCGCUAU 3926 AGCCUGCA CUGAUGAG X CGAA 5611 UAUGCGCUA 6398 AGCGCAUA UGCAGGCU 3935 CAUUCUGG CUGAUGAG X CGAA 5612 UGCAGGCUU 6399 AGCCUGCA CCAGAAUG 25 3936 UCAUUCUG CUGAUGAG X CGAA 5613 GCAGGCUUC 6400 AAGCCUGC CAGAAUGA 3957 GGGAAAGG CUGAUGAG X CGAA 5614 GAUGGGGUC 6401 ACCCCAUC CCUUUCCC 3961 GUGGGGGA CUGAUGAG X CGAA 5615 GGGUCCCUU 6402 30 AGGGACCC UCCCCCAC 3962 UGUGGGGG CUGAUGAG X CGAA 5616 GGUCCCUUU 6403 AAGGGACC CCCCCACA 3963 AUGUGGGG CUGAUGAG X CGAA 5617 GUCCCUUUC 6404 AAAGGGAC CCCCACAU WO 99/50403 PCTIUS99/06507 267 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 3972 CUCUCACA CUGAUGAG X CGAA 5618 CCCCACAUA 6405 AUGUGGGG UGUGAGAG 5 3986 AUAAGAGG CUGAUGAG X CGAA 5619 GAGGGGGUC 6406 ACCCCCUC CCUCUUAU 3990 UGAAAUAA CUGAUGAG X CGAA 5620 GGGUCCCUC 6407 AGGGACCC UUAUUUCA 3992 GUUGAAAU CUGAUGAG X CGAA 5621 GUCCCUCUU 6408 10 AGAGGGAC AUUUCAAC 3993 AGUUGAAA CUGAUGAG X CGAA 5622 UCCCUCUUA 6409 AAGAGGGA UUUCAACU 3995 CGAGUUGA CUGAUGAG X CGAA 5623 CCUCUUAUU 6410 AUAAGAGG UCAACUCG 15 3996 ACGAGUUG CUGAUGAG X CGAA 5624 CUCUUAUUU 6411 AAUAAGAG CAACUCGU 3997 AACGAGUU CUGAUGAG X CGAA 5625 UCUUAUUUC 6412 AAAUAAGA AACUCGUU 4002 UGAGGAAC CUGAUGAG X CGAA 5626 UUUCAACUC 6413 20 AGUUGAAA GUUCCUCA 4005 CAAUGAGG CUGAUGAG X CGAA 5627 CAACUCGUU 6414 ACGAGUUG CCUCAUUG 4006 GCAAUGAG CUGAUGAG X CGAA 5628 AACUCGUUC 6415 AACGAGUU CUCAUUGC 25 4009 CCAGCAAU CUGAUGAG X CGAA 5629 UCGUUCCUC 6416 AGGAACGA AUUGCUGG 4012 AAACCAGC CUGAUGAG X CGAA 5630 UUCCUCAUU 6417 AUGAGGAA GCUGGUUU 4019 AUAUGCCA CUGAUGAG X CGAA 5631 UUGCUGGUU 6418 30 ACCAGCAA UGGCAUAU 4020 GAUAUGCC CUGAUGAG X CGAA 5632 UGCUGGUUU 6419 AACCAGCA GGCAUAUC 4026 AGCUGAGA CUGAUGAG X CGAA 5633 UUUGGCAUA 6420 AUGCCAAA UCUCAGCU WO 99/50403 PCTIUS99/06507 268 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 4028 GUAGCUGA CUGAUGAG X CGAA 5634 UGGCAUAUC 6421 AUAUGCCA UCAGCUAC 5 4030 GAGUAGCU CUGAUGAG X CGAA 5635 GCAUAUCUC 6422 AGAUAUGC AGCUACUC 4035 GGUUAGAG CUGAUGAG X CGAA 5636 UCUCAGCUA 6423 AGCUGAGA CUCUAACC 4038 CCGGGUUA CUGAUGAG X CGAA 5637 CAGCUACUC 6424 10 AGUAGCUG UAACCCGG 4040 UGCCGGGU CUGAUGAG X CGAA 5638 GCUACUCUA 6425 AGAGUAGC ACCCGGCA 4054 CUUCUGUG CUGAUGAG X CGAA 5639 GCAAGAAUC 6426 AUUCUUGC CACAGAAG 15 4084 AAAUGUAU CUGAUGAG X CGAA 5640 AAAAGGCUU 6427 AGCCUUUU AUACAUUU 4085 CAAAUGUA CUGAUGAG X CGAA 5641 AAAGGCUUA 6428 AAGCCUUU UACAUUUG 4087 AGCAAAUG CUGAUGAG X CGAA 5642 AGGCUUAUA 6429 20 AUAAGCCU CAUUUGCU 4091 GUAAAGCA CUGAUGAG X CGAA 5643 UUAUACAUU 6430 AUGUAUAA UGCUUUAC 4092 GGUAAAGC CUGAUGAG X CGAA 5644 UAUACAUUU 6431 AAUGUAUA GCUUUACC 25 4096 UAUGGGUA CUGAUGAG X CGAA 5645 CAUUUGCUU 6432 AGCAAAUG UACCCAUA 4097 UUAUGGGU CUGAUGAG X CGAA 5646 AUUUGCUUU 6433 AAGCAAAU ACCCAUAA 4098 CUUAUGGG CUGAUGAG X CGAA 5647 UUUGCUUUA 6434 30 AAAGCAAA CCCAUAAG 4104 GGUUUUCU CUGAUGAG X CGAA 5648 UUACCCAUA 6435 AUGGGUAA AGAAAACC 4114 CAGGGCUU CUGAUGAG X CGAA 5649 GAAAACCUC 6436 AGGUUUUC AAGCCCUG WO 99/50403 PCT/US99/06507 269 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 4124 UUUUCAGA CUGAUGAG X CGAA 5650 AGCCCUGUA 6437 ACAGGGCU UCUGAAAA 5 4126 UUUUUUCA CUGAUGAG X CGAA 5651 CCCUGUAUC 6438 AUACAGGG UGAAAAAA 4144 GAUCCUUU CUGAUGAG X CGAA 5652 AGGAAGAUA 6439 AUCUUCCU AAAGGAUC 4152 GUCUUAUA CUGAUGAG X CGAA 5653 AAAAGGAUC 6440 10 AUCCUUUU UAUAAGAC 4154 AAGUCUUA CUGAUGAG X CGAA 5654 AAGGAUCUA 6441 AGAUCCUU UAAGACUU 4156 UGAAGUCU CUGAUGAG X CGAA 5655 GGAUCUAUA 6442 AUAGAUCC AGACUUCA 15 4162 GGAACUUG CUGAUGAG X CGAA 5656 AUAAGACUU 6443 AGUCUUAU CAAGUUCC 4163 UGGAACUU CUGAUGAG X CGAA 5657 UAAGACUUC 6444 AAGUCUUA AAGUUCCA 4168 UCUCAUGG CUGAUGAG X CGAA 5658 CUUCAAGUU 6445 20 ACUUGAAG CCAUGAGA 4169 UUCUCAUG CUGAUGAG X CGAA 5659 UUCAAGUUC 6446 AACUUGAA CAUGAGAA 4189 ACAAAAUA CUGAUGAG X CGAA 5660 GGACAUGUC 6447 ACAUGUCC UAUUUUGU 25 4191 GAACAAAA CUGAUGAG X CGAA 5661 ACAUGUCUA 6448 AGACAUGU UUUUGUUC 4193 UUGAACAA CUGAUGAG X CGAA 5662 AUGUCUAUU 6449 AUAGACAU UUGUUCAA 4194 AUUGAACA CUGAUGAG X CGAA 5663 UGUCUAUUU 6450 30 AAUAGACA UGUUCAAU 4195 UAUUGAAC CUGAUGAG X CGAA 5664 GUCUAUUUU 6451 AAAUAGAC GUUCAAUA 4198 GAGUAUUG CUGAUGAG X CGAA 5665 UAUUUUGUU 6452 ACAAAAUA CAAUACUC WO 99/50403 PCT/US99/06507 270 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 4199 AGAGUAUU CUGAUGAG X CGAA 5666 AUUUUGUUC 6453 AACAAAAU AAUACUCU 5 4203 GCAUAGAG CUGAUGAG X CGAA 5667 UGUUCAAUA 6454 AUUGAACA CUCUAUGC 4206 UGGGCAUA CUGAUGAG X CGAA 5668 UCAAUACUC 6455 AGUAUUGA UAUGCCCA 4208 AGUGGGCA CUGAUGAG X CGAA 5669 AAUACUCUA 6456 10 AGAGUAUU UGCCCACU 4228 UUGCUGCC CUGAUGAG X CGAA 5670 UGGCACAUA 6457 AUGUGCCA GGCAGCAA 4244 UCCACAGA CUGAUGAG X CGAA 5671 AAACAAAUA 6458 AUUUGUUU UCUGUGGA 15 4246 AUUCCACA CUGAUGAG X CGAA 5672 ACAAAUAUC 6459 AUAUUUGU UGUGGAAU 4258 CCUUUACA CUGAUGAG X CGAA 5673 GGAAUGCUA 6460 AGCAUUCC UGUAAAGG 4262 GAUGCCUU CUGAUGAG X CGAA 5674 UGCUAUGUA 6461 20 ACAUAGCA AAGGCAUC 4270 CAUCUAUA CUGAUGAG X CGAA 5675 AAAGGCAUC 6462 AUGCCUUU UAUAGAUG 4272 AUCAUCUA CUGAUGAG X CGAA 5676 AGGCAUCUA 6463 AGAUGCCU UAGAUGAU 25 4274 ACAUCAUC CUGAUGAG X CGAA 5677 GCAUCUAUA 6464 AUAGAUGC GAUGAUGU 4287 CUUAAAGG CUGAUGAG X CGAA 5678 AUGUGCCUC 6465 AGGCACAU CCUUUAAG 4291 GUUUCUUA CUGAUGAG X CGAA 5679 GCCUCCCUU 6466 30 AGGGAGGC UAAGAAAC 4292 GGUUUCUU CUGAUGAG X CGAA 5680 CCUCCCUUU 6467 AAGGGAGG AAGAAACC 4293 GGGUUUCU CUGAUGAG X CGAA 5681 CUCCCUUUA 6468 AAAGGGAG AGAAACCC WO 99/50403 PCT/US99/06507 271 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 4305 UAUUCAAA CUGAUGAG X CGAA 5682 AACCCAAUA 6469 AUUGGGUU UUUGAAUA 5 4307 AAUAUUCA CUGAUGAG X CGAA 5683 CCCAAUAUU 6470 AUAUUGGG UGAAUAUU 4308 AAAUAUUC CUGAUGAG X CGAA 5684 CCAAUAUUU 6471 AAUAUUGG GAAUAUUU 4313 AGUGCAAA CUGAUGAG X CGAA 5685 AUUUGAAUA 6472 10 AUUCAAAU UUUGCACU 4315 UGAGUGCA CUGAUGAG X CGAA 5686 UUGAAUAUU 6473 AUAUUCAA UGCACUCA 4316 AUGAGUGC CUGAUGAG X CGAA 5687 UGAAUAUUU 6474 AAUAUUCA GCACUCAU 15 4322 GUAUGAAU CUGAUGAG X CGAA 5688 UUUGCACUC 6475 AGUGCAAA AUUCAUAC 4325 CUUGUAUG CUGAUGAG X CGAA 5689 GCACUCAUU 6476 AUGAGUGC CAUACAAG 4326 UCUUGUAU CUGAUGAG X CGAA 5690 CACUCAUUC 6477 20 AAUGAGUG AUACAAGA 4329 GGAUCUUG CUGAUGAG X CGAA 5691 UCAUUCAUA 6478 AUGAAUGA CAAGAUCC 4336 CACUUGAG CUGAUGAG X CGAA 5692 UACAAGAUC 6479 AUCUUGUA CUCAAGUG 25 4339 GAGCACUU CUGAUGAG X CGAA 5693 AAGAUCCUC 6480 AGGAUCUU AAGUGCUC 4347 UCCAAACG CUGAUGAG X CGAA 5694 CAAGUGCUC 6481 AGCACUUG CGUUUGGA 4351 AUUAUCCA CUGAUGAG X CGAA 5695 UGCUCCGUU 6482 30 ACGGAGCA UGGAUAAU 4352 GAUUAUCC CUGAUGAG X CGAA 5696 GCUCCGUUU 6483 AACGGAGC GGAUAAUC 4357 CUCCAGAU CUGAUGAG X CGAA 5697 GUUUGGAUA 6484 AUCCAAAC AUCUGGAG WO 99/50403 PCT/US99/06507 272 Posi- Seq. I.D. Seq. I.D. tion RZ No. Substrate No. 4360 ACCCUCCA CUGAUGAG X CGAA 5698 UGGAUAAUC 6485 AUUAUCCA UGGAGGGU 5 4369 UGUUUUCA CUGAUGAG X CGAA 5699 UGGAGGGUA 6486 ACCCUCCA UGAAAACA 4379 AUCUUGGC CUGAUGAG X CGAA 5700 GAAAACAUA 6487 AUGUUUUC GCCAAGAU 4388 GAAUUCAU CUGAUGAG X CGAA 5701 GCCAAGAUC 6488 10 AUCUUGGC AUGAAUUC 15 20 25 30 WO 99/50403 PCTIUS99/06507 273 TABLE X: HAIRPIN RIBOZYME AND TARGET SEQUENCES FOR INTEGRIN SUBUNIT BETA 3 Seq. Seq. Position RZ I.D. No. Substrate I.D. No. 98 UCUCUG AGAA GGUU ACCAGAGAAACA 6489 AACCG GUU 6569 X GUACAUUACCUGGUA CAGAGA 5 119 GCAAAC AGAA GCUG ACCAGAGAAACA 6490 CAGCA GAU 6570 X GUACAUUACCUGGUA GUUUGC 284 GUCCGC AGAA GGGC ACCAGAGAAACA 6491 GCCCA GUC 6571 X GUACAUUACCUGGUA GCGGAC 290 CCGGGG AGAA GCGA ACCAGAGAAACA 6492 UCGCG GAC 6572 10 X GUACAUUACCUGGUA CCCCGG 313 CGGGUC AGAA GCGC ACCAGAGAAACA 6493 GCGCU GAC 6573 X GUACAUUACCUGGUA GACCCG 322 CCUGCC AGAA GGGU ACCAGAGAAACA 6494 ACCCG GCU 6574 X GUACAUUACCUGGUA GGCAGG 15 388 GAGGG AGAA GUGG ACCAGAGAAACA 6495 CCACC GCU 6575 X GUACAUUACCUGGUA CCCUCU 465 GGGGCG AGAA GCGG ACCAGAGAAACA 6496 CCGCG GCC 6576 X GUACAUUACCUGGUA CGCCCC 469 CAACGG AGAA GGCC ACCAGAGAAACA 6497 GGCCC GCC 6577 20X GUACAUUACCUGGUA CCGUUG 474 GGACGC AGAA GGGC ACCAGAGAAACA 6498 GCCCC GUU 6578 X GUACAUUACCUGGUA GCGUCC 513 UUCCGC AGAA GGAG ACCAGAGAAACA 6499 CUCCC GCU 6579 X GUACAUUACCUGGUA GCGGAA 25 527 GCCCGC AGAA GCUU ACCAGAGAAACA 6500 AAGCG GCC 6580 X GUACAUUACCUGGUA GCGGGC 578 CAUCUC AGAA GCCU ACCAGAGAAACA 6501 AGGCG GAC 6581 X GUACAUUACCUGGUA GAGAUG 595 GGCCGC AGAA GCGC ACCAGAGAAACA 6502 GCGCG GCC 6582 30 X GUACAUUACCUGGUA GCGGCC 601 GGCCGG AGAA GCGG ACCAGAGAAACA 6503 CCGCG GCC 6583 X GUACAUUACCUGGUA CCGGCC WO 99/50403 PCT/US99/06507 274 Seq. Seq. Position RZ I.D. No. Substrate I.D. No. 607 CAGAGC AGAA GGGG ACCAGAGAAACA 6504 CCCCG GCC 6584 X GUACAUUACCUGGUA GCUCUG 5 610 GCCCAG AGAA GCCG ACCAGAGAAACA 6505 CGGCC GCU 6585 X GUACAUUACCUGGUA CUGGGC 678 CUGCCG AGAA GGAG ACCAGAGAAACA 6506 CUCCG GCU 6586 X GUACAUUACCUGGUA CGGCAG 694 UGGGGC AGAA GCGA ACCAGAGAAACA 6507 UCGCA GCU 6587 10 X GUACAUUACCUGGUA GCCCCA 697 UCCUGG AGAA GCUG ACCAGAGAAACA 6508 CAGCU GCC 6588 X GUACAUUACCUGGUA CCAGGA 728 CUCCAA AGAA GCAA ACCAGAGAAACA 6509 UUGCG GAC 6589 X GUACAUUACCUGGUA UUGGAG 15 800 GGUCC AGAA GGC ACCAGAGAAACA X 6510 GCNCG GUC 6590 GUACAUUACCUGGUA GGANCC 920 CGCGGC AGAA GGGA ACCAGAGAAACA 6511 UCCCG GCC 6591 X GUACAUUACCUGGUA GCCGCG 923 CGCCGC AGAA GCCG ACCAGAGAAACA 6512 CGGCC GCC 6592 20 X GUACAUUACCUGGUA GCGGCG 1006 UCCUUG AGAA GACC ACCAGAGAAACA 6513 GGUCG GNC 6593 X GUACAUUACCUGGUA CAAGGA 1020 UUCCUG AGAA GUCG ACCAGAGAAACA 6514 CGACU GCC 6594 X GUACAUUACCUGGUA CAGGAA 25 1063 CCAAGG AGAA GGAA ACCAGAGAAACA 6515 UUCCC GCC 6595 X GUACAUUACCUGGUA CCUUGG 1295 CCUGGG AGAA GAGG ACCAGAGAAACA 6516 CCUCU GCU 6596 X GUACAUUACCUGGUA CCCAGG 1307 UGCAGG AGAA GCCC ACCAGAGAAACA 6517 GGGCA GAC 6597 30 X GUACAUUACCUGGUA CCUGCA 1396 GUGCGC AGAA GCCA ACCAGAGAAACA 6518 UGGCU GCU 6598 X GUACAUUACCUGGUA GCGCAC 1412 CCUGAC AGAA GACG ACCAGAGAAACA 6519 CGUCA GCC 6599 X GUACAUUACCUGGUA GUCAGG WO 99/50403 PCTIUS99/06507 275 Seq. Seq. Position RZ I.D. No. Substrate I.D. No. 1435 CAAAGA AGAA GAAU ACCAGAGAAACA 6520 AUUCG GCC 6600 X GUACAUUACCUGGUA UCUUUG 5 1481 ACCCCG AGAA GUGC ACCAGAGAAACA 6521 GCACA GCC 6601 X GUACAUUACCUGGUA CGGGGU 1494 ACCACG AGAA GCAA ACCAGAGAAACA 6522 UUGCU GCC 6602 X GUACAUUACCUGGUA CGUGGU 1561 GGCCCC AGAA GACC ACCAGAGAAACA 6523 GGUCU GCU 6603 10 X GUACAUUACCUGGUA GGGGCC 1570 GGCAGA AGAA GCCC ACCAGAGAAACA 6524 GGGCC GCC 6604 X GUACAUUACCUGGUA UCUGCC 1576 CUCUGA AGAA GAGG ACCAGAGAAACA 6525 CCUCU GCC 6605 X GUACAUUACCUGGUA UCAGAG 15 1625 GAGUAC AGAA GUUU ACCAGAGAAACA 6526 AAACU GUA 6606 X GUACAUUACCUGGUA GUACUC 1726 CUGGGC AGAA GAGC ACCAGAGAAACA 6527 GCUCU GUC 6607 X GUACAUUACCUGGUA GCCCAG 1760 GCAGUG AGAA GAGA ACCAGAGAAACA 6528 UCUCG GCU 6608 20 X GUACAUUACCUGGUA CACUGC 1776 CCAGGA AGAA GAAG ACCAGAGAAACA 6529 CUUCU GCC 6609 X GUACAUUACCUGGUA UCCUGG 1808 UCGGGA AGAA GAGC ACCAGAGAAACA 6530 GCUCA GCC 6610 X GUACAUUACCUGGUA UCCCGA 25 1848 UUAGCC AGAA GUGG ACCAGAGAAACA 6531 CCACG GCC 6611 X GUACAUUACCUGGUA GGCUAA 1882 UGGUGA AGAA GCGU ACCAGAGAAACA 6532 ACGCG GUU 6612 X GUACAUUACCUGGUA UCACCA 1933 GAGGUG AGAA GAUC ACCAGAGAAACA 6533 GAUCC GCC 6613 30 X GUACAUUACCUGGUA CACCUC 1943 UUGGGA AGAA GAGG ACCAGAGAAACA 6534 CCUCA GCC 6614 X GUACAUUACCUGGUA UCCCAA 2170 CCUGGC AGAA GCGA ACCAGAGAAACA 6535 UCGCU GUC 6615 X GUACAUUACCUGGUA GCCAGG WO 99/50403 PCTIUS99/06507 276 Seq. Seq. Position RZ I.D. No. Substrate I.D. No. 2203 GCAGUG AGAA GAAA ACCAGAGAAACA 6536 UUUCA GCU 6616 X GUACAUUACCUGGUA CACUGC 5 2219 CCGGGA AGAA GAGG ACCAGAGAAACA 6537 CCUCC GCU 6617 X GUACAUUACCUGGUA UCCCGG 2245 GGCUGA AGAA GGAG ACCAGAGAAACA 6538 CUCCU GCC 6618 X GUACAUUACCUGGUA UCAGCC 2251 UCGGGA AGAA GAGG ACCAGAGAAACA 6539 CCUCA GCC 6619 10 X GUACAUUACCUGGUA UCCCGA 2373 AAGGCA AGAA GAUC ACCAGAGAAACA 6540 GAUCA GCC 6620 X GUACAUUACCUGGUA UGCCUU 2377 GGCCAA AGAA GGCU ACCAGAGAAACA 6541 AGCCU GCC 6621 X GUACAUUACCUGGUA UUGGCC 15 2456 CAUAUC AGAA GUAA ACCAGAGAAACA 6542 UUACA GUU 6622 X GUACAUUACCUGGUA GAUAUG 2521 CAGCUG AGAA GUUU ACCAGAGAAACA 6543 AAACA GAU 6623 X GUACAUUACCUGGUA CAGCUG 2526 ACUAUC AGAA GAUC ACCAGAGAAACA 6544 GAUCA GCU 6624 20 X GUACAUUACCUGGUA GAUAGU 2553 UCAUCA AGAA GCUC ACCAGAGAAACA 6545 GAGCA GUC 6625 X GUACAUUACCUGGUA UGAUGA 2557 AUAGUC AGAA GACU ACCAGAGAAACA 6546 AGUCU GAU 6626 X GUACAUUACCUGGUA GACUAU 25 2595 UCCCAG AGAA GAAU ACCAGAGAAACA 6547 AUUCU GCC 6627 X GUACAUUACCUGGUA CUGGGA 2623 AGCAGC AGAA GACC ACCAGAGAAACA 6548 GGUCA GAU 6628 X GUACAUUACCUGGUA GCUGCU 2629 AUAGCC AGAA GCAU ACCAGAGAAACA 6549 AUGCU GCU 6629 30 X GUACAUUACCUGGUA GGCUAU 2738 AUCCUG AGAA GGAC ACCAGAGAAACA 6550 GUCCU GUC 6630 X GUACAUUACCUGGUA CAGGAU 2811 UUAGAA AGAA GUGA ACCAGAGAAACA 6551 UCACA GUC 6631 X GUACAUUACCUGGUA UUCUAA WO 99/50403 PCT/US99/06507 277 Seq. Seq. Position RZ I.D. No. Substrate I.D. No. 2982 UGCCCA AGAA GGUC ACCAGAGAAACA 6552 GACCA GCU 6632 X GUACAUUACCUGGUA UGGGCA 5 3045 UCUGUG AGAA GAUC ACCAGAGAAACA 6553 GAUCU GUU 6633 X GUACAUUACCUGGUA CACAGA 3052 AGAUUA AGAA GUGA ACCAGAGAAACA 6554 UCACA GAU 6634 X GUACAUUACCUGGUA UAAUCU 3138 AAACAC AGAA GUAC ACCAGAGAAACA 6555 GUACA GUA 6635 10 X GUACAUUACCUGGUA GUGUUU 3169 CUGGAA AGAA GACU ACCAGAGAAACA 6556 AGUCA GAC 6636 X GUACAUUACCUGGUA UUCCAG 3211 AGUAGA AGAA GAUU ACCAGAGAAACA 6557 AAUCA GUU 6637 X GUACAUUACCUGGUA UCUACU 15 3262 CCAGGG AGAA GAAG ACCAGAGAAACA 6558 CUUCA GAU 6638 X GUACAUUACCUGGUA CCCUGG 3278 CCCACC AGAA GCUU ACCAGAGAAACA 6559 AAGCA GAU 6639 X GUACAUUACCUGGUA GGUGGG 3382 CCCCAA AGAA GACU ACCAGAGAAACA 6560 AGUCU GCU 6640 20 X GUACAUUACCUGGUA UUGGGG 3510 AAUUAG AGAA GAAU ACCAGAGAAACA 6561 AUUCU GAC 6641 X GUACAUUACCUGGUA CUAAUU 3703 ACAGCC AGAA GGAG ACCAGAGAAACA 6562 CUCCU GUA 6642 X GUACAUUACCUGGUA GGCUGU 25 3750 UGAGGA AGAA GAGG ACCAGAGAAACA 6563 CCUCA GUU 6643 X GUACAUUACCUGGUA UCCUCA 3796 CAUUUA AGAA GCAU ACCAGAGAAACA 6564 AUGCU GAU 6644 X GUACAUUACCUGGUA UAAAUG 3948 GACCCC AGAA GUUU ACCAGAGAAACA 6565 AAACU GAU 6645 30 X GUACAUUACCUGGUA GGGGUC 4121 UUCAGA AGAA GGGC ACCAGAGAAACA 6566 GCCCU GUA 6646 X GUACAUUACCUGGUA UCUGAA 4216 GUGCCA AGAA GUGG ACCAGAGAAACA 6567 CCACU GCC 6647 X GUACAUUACCUGGUA UGGCAC WO 99/50403 PCT/US99/06507 278 Seq. Seq. Position RZ I.D. No. Substrate I.D. No. 4348 UAUCCA AGAA GAGC ACCAGAGAAACA 6568 GCUCC GUU 6648 X GUACAUUACCUGGUA UGGAUA 5 10 15 20 25 30

Claims (59)

1. An enzymatic nucleic acid molecule with RNA cleaving activity, wherein said enzymatic nucleic acid molecule specifically cleaves RNA encoded by an aryl 5 hydrocarbon nuclear transporter (ARNT) gene.

2. An enzymatic nucleic acid molecule with RNA cleaving activity, wherein said enzymatic nucleic acid molecules specifically cleaves RNA encoded by an integrin subunit beta

3 (P3) gene. 10 3. An enzymatic nucleic acid molecule with RNA cleaving activity, wherein said enzymatic nucleic acid molecules cleaves RNA encoded by a integrin subunit alpha 6 (cx6) gene.

4. An enzymatic nucleic acid molecule with RNA 15 cleaving activity, wherein said enzymatic nucleic acid molecules cleaves RNA encoded by a Tie-2 gene.

5. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid molecule is in a hammerhead configuration. 20

6. The enzymatic nucleic acid molecule of claim 5, wherein said enzymatic nucleic acid molecule comprises a stem II region of length greater than or equal to 2 base pairs.

7. The enzymatic nucleic acid molecule of any of 25 claims 1-4, wherein said enzymatic nucleic acid molecule is in a hairpin configuration. WO 99/50403 PCTIUS99/06507 280

8. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid is in a hepatitis delta virus, group I intron, group II intron, VS nucleic acid or RNase P nucleic acid configuration. 5

9. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic molecule is a DNAzyme.

10. The enzymatic nucleic acid of claim 7, wherein said enzymatic nucleic acid molecule comprises a stem II 10 region of length between three and seven base-pairs.

11. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid molecule comprises between 12 and 100 bases complementary to said RNA. 15

12. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid molecule comprises between 14 and 24 bases complementary to said mRNA.

13. The enzymatic nucleic acid molecule of claim 5 20 wherein said enzymatic nucleic acid molecule consists essentially of any sequence defined as Seq. I.D. Nos 1 393, 911-1611, 2449-3587, and 4915-5701.

14 The enzymatic nucleic acid molecule of claim 7, wherein said enzymatic nucleic acid molecule consists 25 essentially of any sequence defined as Seq. ID 787-848,

2313-2380, 4727-4820 and 6489-6568.

15. A mammalian cell including an enzymatic nucleic acid molecule of any of claims 1-4. WO 99/50403 PCTIUS99/06507 281

16. The mammalian cell of claim 15, wherein said mammalian cell is a human cell.

17. An expression vector comprising nucleic acid sequence encoding at least one enzymatic nucleic acid 5 molecule of any of claims 1-4 in a manner which allows expression of that enzymatic nucleic acid molecule.

18. A mammalian cell including an expression vector of claim 17.

19. The mammalian cell of claim 18, wherein said 10 mammalian cell is a human cell.

20. A method for treatment of cancer, diabetic retinopathy, age related macular degeneration (ARMD), inflammation, and arthritis comprising the step of administering to a patient an enzymatic nucleic acid 15 molecule of any of claims 1-4.

21. A method for treatment of cancer comprising the step of administering to a patient, an expression vector of claim 17.

22. A method for the treatment of cancer, diabetic 20 retinopathy, age related macular degeneration (ARMD), inflammation, and arthritis comprising the step of administering to a patient an expression vector of claim 17.

23. A method for treatment of cancer comprising the 25 steps of: a) isolating cells from a patient; b) administering to said cells an enzymatic nucleic acid molecule of any of claims 1-4; and c) introducing said cells back into said patient. WO 99/50403 PCT/US99/06507 282

24. A pharmaceutical composition comprising the enzymatic nucleic acid molecule of any of claims 1-4.

25. A method of treatment of a patient having a condition associated with an elevated level of aryl 5 hydrocarbon nuclear transporter (ARNT), comprising the step of administration to said patient an enzymatic nucleic acid molecule of claim 1.

26. A method of treatment of a patient having a condition associated with the level of Tie-2 comprising 10 the step of administration to said patient an enzymatic nucleic acid molecule of claim 2.

27. A method of treatment of a patient having a condition associated with the level of integrin subunit alpha 6, comprising the step of administration to said 15 patient an enzymatic nucleic acid molecule of claim 3.

28. A method of treatment of a patient having a condition associated with the level of integrin subunit beta 3 comprising the step of administration to said patient an enzymatic nucleic acid molecule of claim 4. 20

29. A method of treatment of a patient having a condition associated with the level of aryl hydrocarbon nuclear transporter (ARNT), comprising the steps of: (a)contacting cells of said patient with an enzymatic nucleic acid molecule of claim 1; and (b) administering 25 to said patient one or more additional drugs.

30. A method of treatment of a patient having a condition associated with the level of Tie-2, comprising the steps of: (a)contacting cells of said patient with an enzymatic nucleic acid molecule of claim 2; and (b) WO 99/50403 PCTIUS99/06507 283 administering to said patient one or more additional drugs.

31. A method of treatment of a patient having a condition associated with the level of integrin subunit 5 alpha 6, comprising the steps of: (a)contacting cells of said patient with an enzymatic nucleic acid molecule of claim 3; and (b) administering to said patient one or more additional drugs.

32. A method of treatment of a patient having a 10 condition associated with the level of integrin subunit beta 3, comprising the steps of: (a)contacting cells of said patient with an enzymatic nucleic acid molecule of claim 4; and (b) administering to said patient one or more additional drugs. 15

33. The enzymatic nucleic acid molecule of claim 5, wherein said enzymatic nucleic acid molecule comprises at least five ribose residues, phosphorothioate linkages in at least three of the 5' terminal nucleotides, a 2'-C allyl modification at position No. 4 of said nucleic acid, 20 at least ten 2'-O-methyl modifications, and a 3'- end modification.

34. The enzymatic nucleic acid of claim 33, wherein said enzymatic nucleic acid comprises a 3'-3' linked inverted ribose moiety at said 3' end. 25

35. The enzymatic nucleic acid molecule of claim 5, wherein said enzymatic nucleic acid molecule comprises at least five ribose residues; phosphorothioate linkages at least three of the 5' terminal nucleotides 2'-amino modification at position No. 4 and/or at position No. 7 of WO 99/50403 PCT/US99/06507 284 said enzymatic nucleic acid molecule; at least ten 2'-0 methyl modifications; and a 3'- end modification.

36. The enzymatic nucleic acid molecule of claim 5, wherein said enzymatic nucleic acid molecule comprises at 5 least five ribose residues; phosphorothioate linkages at least three of the 5' terminal nucleotides, abasic substitution at position No. 4 and/or at position No. 7 of said enzymatic nucleic acid molecule; at least ten 2'-0 methyl modifications; comprises a 3'-end modification. 10

37. The enzymatic nucleic acid molecule of claim 5, wherein said enzymatic nucleic acid molecule comprises of at least five ribose residues; phosphorothioate linkages at least three of the 5' terminal nucleotides; a 6-methyl uridine substitution at position No. 4 and/or at position 15 No. 7 of said enzymatic nucleic acid molecule; at least ten 2'-O-methyl modifications; and comprises a 3' end modification.

38. A method for modulating expression of ARNT gene in a mammalian cell comprising the step of administering 20 to said cell an enzymatic nucleic acid molecule of claim 1.

39. A method for modulating expression of integrin subunit beta 3 in a mammalian cell comprising the step of administering to said cell an enzymatic nucleic acid 25 molecule of claim 2.

40. A method for modulating expression of integrin subunit alpha 6 in a mammalian cell comprising the step of administering to said cell an enzymatic nucleic acid molecule of claim 3. WO 99/50403 PCT/US99/06507 285

41. A method for modulating expression of Tie-2 in a mammalian cell comprising the step of administering to said cell an enzymatic nucleic acid molecule of claim 4.

42. A method of cleaving an ARNT RNA molecule 5 comprising the step of, contacting the enzymatic nucleic acid molecule of claim 1 with said ARNT RNA molecule under conditions suitable for the cleavage of said ARNT RNA molecule.

43. A method of cleaving a integrin subunit beta 3 10 RNA molecule comprising the step of, contacting the enzymatic nucleic acid molecule of claim 2 with said integrin subunit beta 3 RNA molecule under conditions suitable for the cleavage of said integrin subunit beta 3 RNA molecule. 15

44. A method of cleaving a integrin subunit alpha 6 RNA molecule comprising the step of, contacting the enzymatic nucleic acid molecule of claim 3 with said integrin subunit alpha 6 RNA molecule under conditions suitable for the cleavage of said integrin subunit alpha 6 20 RNA molecule.

45. A method of cleaving a Tie-2 RNA molecule comprising the step of, contacting the enzymatic nucleic acid molecule of claim 4 with said Tie-2 RNA molecule under conditions suitable for the cleavage of said Tie-2 25 RNA molecule.

46. The method of any of claims 42-45, wherein said cleavage is carried out in the presence of a divalent cation. WO 99/50403 PCT/US99/06507 286

47. The method of claim 46, wherein said divalent cation is Mg 2 +.

48. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid molecule 5 is chemically synthesized.

49. The expression vector of claim 17, wherein said expression vector comprises: a) a transcription initiation region; b) a transcription termination region; 10 c) a gene encoding at least one said nucleic acid molecule; 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 15 acid molecule.

50. The expression vector of claim 17, wherein said expression vector comprises: a) a transcription initiation region; b) a transcription termination region; 20 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 25 initiation region, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

51. The expression vector of claim 17, wherein said expression vector comprises: 30 a) a transcription initiation region; b) a transcription termination region; WO 99/50403 PCT/US99/06507 287 c) an intron; d) a gene encoding at least one said nucleic acid molecule; and wherein said gene is operably linked to said 5 initiation region, said intron and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

52. The expression vector of claim 18, wherein said vector comprises: 10 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 15 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 intron, said open reading frame and said termination region, in a manner which allows 20 expression and/or delivery of said nucleic acid molecule.

53. The enzymatic nucleic acid molecule of claim 1, wherein said enzymatic nucleic acid comprises sequences that are complementary to any of sequences defined as Seq ID Nos 394-786 and 849-910. 25

54. The enzymatic nucleic acid molecule of claim 2, wherein said enzymatic nucleic acid comprises sequences that are complementary to any of sequences defined as Seq ID Nos 5702-6488 and 6569-6648.

55. The enzymatic nucleic acid molecule of claim 3, 30 wherein said enzymatic nucleic acid comprises sequences WO 99/50403 PCT/US99/06507 288 that are complementary to any of sequences defined as Seq ID Nos 3588-4726 and 4821-4914.

56. The enzymatic nucleic acid molecule of claim 4, wherein said enzymatic nucleic acid comprises sequences 5 that are complementary to any of sequences defined as Seq ID Nos 1612-2312 and 2381-2448.

57. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid comprises at least one 2'-sugar modification. 10

58. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid comprises at least one nucleic acid base modification.

59. The enzymatic nucleic acid molecule of any of claims 1-4, wherein said enzymatic nucleic acid comprises 15 at least one phosphorothioate modification.