AU4232700A - Regulation of repressor genes using nucleic acid molecules - Google Patents

Description

WO 00/61729 1 PCT/USOO/09721 DESCRIPTION REGULATION OF REPRESSOR GENES USING NUCLEIC ACID MOLECULES 5 Background of the Invention This invention relates to a novel method for the inhibition of repressor genes. Specifically, inhibition of these repressor genes allows for the increased expression of beneficially gene products. Increasing the expression of beneficial gene products may be useful as therapeutic treatments for a wide range of indications. 10 The following is a discussion of relevant art, none of which is admitted to be prior art to the present invention. RNA synthesis in a biological system involves a number of regulatory steps. For instance in a eukaryotic cell, RNA is synthesized from DNA genes via a process termed transcription. Transcription of RNA is an exquisitely regulated process. 15 Transcription may be positively regulated when the RNA synthesis is stimulated or negatively regulated when the RNA synthesis is inhibited. This level of RNA synthesis regulation is facilitated by the interaction of one or more protein factors that generally exert their effect on transcription by interacting with specific cis acting elements in the gene. While, positive regulation of gene expression is far 20 more prevalent in eukaryotic cells, negative regulation plays an important role for many genes. These protein factors involved in negative regulation ("repressors") generally bind to cis-acting elements, usually upstream to genes, and cause the down regulation of that gene's transcription into RNA ("repression"). Only when these repressors are released from their targets can unhindered gene expression take place. 25 Repressors can also function via other mechanisms such as interacting with protein factors involved in transcription thereby blocking transcription (e.g. protein-protein interaction; modification). A number of genes have been identified in eukaryotic systems that encode repressors. A few non-limiting examples of these repressor genes include: WO 00/61729 2 PCTUSOO/09721 GATA Transcription Factors: Currently 5 factors make up the human GATA family of transcription factors: hGATA-1 (also known as Eryfl, GF-1, or NF-E1) (Trainor et al., 1990, Nature 343, 92-96; Genbank Accession No. X17254); hGATA-2 (Dorfman et al., 1992, J. Biol. Chem. 167, 1279-1285; Genbank Accession No. 5 M77810); hGATA-3 (Joulin et al., 1991, EMBO J. 10, 1809-1816; Genbank Accession No. X58072); hGATA-4 (Genbank Accession No. L34357); and hGATA 6 (Huggon et al., 1997, Biochim. Biophys. Acta 1353, 98-102; Genbank Accession No.X95701). The GATA element or binding region for the GATA protein is present ~30bp upstream of the erythropoietin (Epo) gene. Transfection of QT6 cells 10 with hGATA-1, -2, and -3 have shown that all three factors were able to bind to the GATA element. In addition, all three factors were shown to down regulate the expression of Erythropoietin in Hep3B cells (Imagawa et al, 1996, Acta Haematol. 95, 248-256). EAR3/COUP-TF-1: EAR3/COJP-TF-1 (Miyajima et al., 1988, Nucleic Acids 15 Research 16, 11057-11074; Genbank Accession No.X12795) has been shown to bind to the promoter region of Erythropoietin gene and negatively regulate its expression. This transcription factor appears to compete with hepatic nuclear factor 4 (HNF-4) which is believed to positively regulate Epo expression (Galson et al., 1995, Mol. Cell Biol. 15, 2135-2144). 20 TR2 & TR2-11 Orphan Receptors: TR2 orphan receptor (Chang et al., 1989, Biochem. Biophys. Res. Commun. 165, 735-741; Genbank Accession Co. M29959) and TR2-11 orphan receptor (Chang et al., supra; Genbank Accession No. M29960) are another set of transcription factors believed to negatively regulate Epo expression. The isolated TR2 cDNA encodes for a 603 amino acid protein with a 25 mass of 67 kDa. This protein is believed to bind to a 3' enhancer region of the Epo gene and repress the expression of Epo (Lee et al., 1996, J. Biol. Chem. 271, 10405 10412). CCAAT Displacement Protein (CDP): CDP (Neufeld et al., 1992, Nature Genet. 1, 50-55; Genbank Accession No. M74099) is a 180-200 kDa protein that has been 30 shown to negatively regulate a number of genes including gamma-globin, NCAM, and gp9l-phox gene, neutrophil collagenase, neutrophil gelatinase, and granulocyte colony stimulating factor (G-CSF) (Khanna-Gupta et al., 1997, Blood 90, 2784- WO 00/61729 3 PCT/US00/09721 2795). Elevated levels of G-CSF would be beneficial for treatment during myelosuppressive chemotherapy, AIDS, and chronic neutropenia. Genesis: Also known as HNF-3/Forkhead, Genesis is a member of the winged helix transcriptional regulatory family and is believed to function as a repressor gene with 5 activity in embryonic differentiation in drosophilia (Sutton et al.,1996, J. Biol. Chem. 271, 23126-23133). Studies in 32D cells indicate that protein products of the Genesis gene may inhibit G-CSF gene expression (Xu et al., 1997, Leukemia 12, 207-212). A human homolog of this gene may have the same effect in human cells and is likely to regulate G-CSF gene expression. 10 Interferon regulatory Factor-2 (IRF-2): IRF-2 (Itoh et al., 1989, Nucleic Acids Research 17, 8372; Genbank Accession No. X15949) is a member of the interferon regulatory factors of which more than 10 members exist. IRF-2 is believed to play a role in the regulation of expression for interferon-beta, interferon-alpha, and MHC class I (Nguyen et. al., 1997, Cytokine & Growth Factor Reviews 8, 293-312). The 15 DNA binding domain of IRF-2 is located within the N-terminus of the protein. Imagawa et al., 1997, Blood 4, 1430-1439, describes the use an antisense phosphorothioate oligodeoxynucleotide having the sequence CGGGCGCCACCTCCATGGCCGGCCGGGCGG to inhibit hGATA-2 transcription factor expression in Hep3B cells. 20 Summary Of The Invention The invention features novel nucleic acid-based techniques (e.g., enzymatic nucleic acid molecules, antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups). In one aspect, the invention features use of one or more of the nucleic acid 25 based techniques to inhibit the expression of repressor genes. Inhibition of the repressor gene can then result in the increased expression of genes repressed by these repressor genes. By "repressor genes" is meant genes whose expression can directly or indirectly down regulate or repress or suppress the expression of other genes. 30 By "inhibit" it is meant that the activity of repressor genes or level of mRNAs or equivalent RNAs encoding repressor genes is reduced below that WO 00/61729 4 PCT/USOO/09721 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 attenuated nucleic acid molecule that is able to bind to the same site on the mRNA, but is unable to cleave that RNA. In another embodiment, inhibition 5 with nucleic acid molecules, including enzymatic nucleic acid and antisense molecules, is preferably greater than that observed in the presence of for example, an oligonucleotide with scrambled sequence or with mismatches. In another embodiment, inhibition of repressor genes with the nucleic acid molecule of the instant invention is greater than in the presence of the nucleic acid molecule than in 10 its absence. By "antisense nucleic acid" it is meant a non-enzymatic nucleic acid molecule that binds to target RNA by means of RNA-RNA or RNA-DNA or RNA PNA (protein nucleic acid; Egholm et al., 1993 Nature 365, 566) interactions and alters the activity of the target RNA (for a review see Stein and Cheng, 1993 Science 15 261, 1004). By "2-5A antisense chimera" it is meant, an antisense oligonucleotide containing a 5' phosphorylated 2'-5'-linked adenylate residues. These chimeras bind to target RNA in a sequence-specific manner and activate a cellular 2-5A-dependent ribonuclease which, in turn, cleaves the target RNA (Torrence et al., 1993 Proc. 20 Natl. Acad. Sci. USA 90, 1300). By "triplex DNA" it is meant an oligonucleotide that can bind to a double stranded DNA in a sequence-specific manner to form a triple-strand helix. Formation of such triple helix structure has been shown to inhibit transcription of the targeted gene (Duval-Valentin et al., 1992 Proc. Natl. A cad. Sci. USA 89, 504). 25 By "gene" it is meant a nucleic acid that encodes an RNA. By "enzymatic nucleic acid" it is meant a nucleic acid molecule capable of catalyzing reactions including, but not limited to, site-specific cleavage and/or ligation of other nucleic acid molecules, cleavage of peptide and amide bonds, and trans-splicing. Such a molecule with endonuclease activity may have 30 complementarity in a substrate binding region to a specified gene target, and also has WO 00/61729 5 PCT/USOO/09721 an enzymatic activity that specifically cleaves RNA or DNA in that target. That is, the nucleic acid molecule with endonuclease activity is able to intramolecularly or intermolecularly cleave RNA or DNA and thereby inactivate a target RNA or DNA molecule. This complementarity functions to allow sufficient hybridization of the 5 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 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, 10 catalytic oligonucleotides, nucleozyme, DNAzyme, RNA enzyme, endoribonuclease, 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 limiting in the invention and those skilled in the art will recognize that all that is important in 15 an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target nucleic acid regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart a nucleic acid cleaving activity to the molecule (Cech et al., U.S. Patent No. 4,987,071; Cech et al., 1988, JAMA). 20 By "enzymatic portion" or "catalytic domain" is meant that portion/region of the ribozyme essential for cleavage of a nucleic acid substrate (for example see Figure 1). By "substrate binding arm" or "substrate binding domain" is meant that portion/region of a ribozyme which is complementary to (i.e., able to base-pair with) 25 a 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 and 3. That is, these arms contain sequences within a ribozyme which are intended to bring ribozyme and target RNA together through complementary base-pairing interactions. The ribozyme of the invention may have 30 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 four WO 00/61729 6 PCT/USOO/09721 nucleotides; specifically preferably 12-100 nucleotides; more preferably 14-24 nucleotides long. If two binding arms are chosen, the design is such that the length of the binding arms are symmetrical (i.e., each of the binding arms is of the same length; e.g., five and five nucleotides, six and six nucleotides or seven and seven 5 nucleotides long) or asymmetrical (i.e., the binding arms are of different length; e.g., six and three nucleotides; three and six nucleotides long; four and five nucleotides long; four and six nucleotides long; four and seven nucleotides long; and the like). In one of the preferred embodiments of the inventions herein, the enzymatic nucleic acid molecule is formed in a hammerhead or hairpin motif, but may also be 10 formed in the motif of a hepatitis 6 virus, group I intron, group II intron or RNase P RNA (in association with an RNA guide sequence), Neurospora VS RNA, DNAzymes, NCH cleaving motifs, or G-cleavers. Examples of such hammerhead motifs are described by Dreyfus, supra, Rossi et al., 1992, AIDS Research and Human Retroviruses 8, 183; of hairpin motifs by Hampel et al., EP0360257, Hampel 15 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; Chowrira & McSwiggen, US. Patent No. 5,631,359; of the hepatitis 6 virus motif is described by Perrotta and Been, 1992 Biochemistry 31, 16; of the RNase P motif by Guerrier-Takada et al., 1983 Cell 35, 849; Forster and Altman, 1990, 20 Science 249, 783; Li and Altman, 1996, Nucleic Acids Res. 24, 835; Neurospora VS RNA ribozyme motif is described by Collins (Saville and Collins, 1990 Cell 61, 685-696; Saville and Collins, 1991 Proc. Natl. Acad. Sci. USA 88, 8826-8830; Collins and Olive, 1993 Biochemistry 32, 2795-2799; Guo and Collins, 1995, EMBO. J. 14, 363); Group II introns are described by Griffin et al., 1995, Chem. 25 Biol. 2, 761; Michels and Pyle, 1995, Biochemistry 34, 2965; Pyle et al., International PCT Publication No. WO 96/22689; of the Group I intron by Cech et al., U.S. Patent 4,987,071 and of DNAzymes by Usman et al., International PCT Publication No. WO 95/11304; Chartrand et al., 1995, NAR 23, 4092; Breaker et al., 1995, Chem. Bio. 2, 655; Santoro et al., 1997, PNAS 94, 4262. NCH cleaving 30 motifs are described in Ludwig & Sproat, International PCT Publication No. WO 98/58058; and G-cleavers are described in Kore et al., 1998, Nucleic Acids Research 26, 4116-4120. These specific motifs are not limiting in the invention and those WO 00/61729 7 PCT/USOO/09721 skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart 5 an RNA cleaving activity to the molecule (Cech et al., U.S. Patent No. 4,987,071). In preferred embodiments of the present invention, a nucleic acid molecule, e.g., an antisense molecule, a triplex DNA, or a ribozyme, is 13 to 100 nucleotides in length, e.g., in specific embodiments 35, 36, 37, or 38 nucleotides in length (e.g., for particular ribozymes). In particular embodiments, the nucleic acid molecule is 15 10 100, 17-100, 20-100, 21-100, 23-100, 25-100, 27-100, 30-100, 32-100, 35-100, 40 100, 50-100, 60-100, 70-100, or 80-100 nucleotides in length. Instead of 100 nucleotides being the upper limit on the length ranges specified above, the upper limit of the length range can be, for example, 30, 40, 50, 60, 70, or 80 nucleotides. Thus, for any of the length ranges, the length range for particular embodiments has 15 lower limit as specified, with an upper limit as specified which is greater than the lower limit. For example, in a particular embodiment, the length range can be 35-50 nucleotides in length. All such ranges are expressly included. Also in particular embodiments, a nucleic acid molecule can have a length which is any of the lengths specified above, for example, 21 nucleotides in length. 20 By "equivalent" RNA to repressor genes is meant to include those naturally occurring RNA molecules having homology (partial or complete) to repressor genes or encoding for proteins with similar function as repressor genes in various animals, including human, rodent, primate, rabbit and pig. The equivalent RNA sequence also includes in addition to the coding region, regions such as 5'-untranslated region, 25 3'-untranslated region, introns, intron-exon junction and the like. By "complementarity" is meant that a nucleic acid can form hydrogen bond(s) with another RNA sequence by either traditional Watson-Crick or other non traditional types. In reference to the nucleic molecules of the present invention, the binding free energy for a nucleic acid molecule with its target or complementary 30 sequence is sufficient to allow the relevant function of the nucleic acid to proceed, e.g., ribozyme cleavage, antisense or triple helix inhibition. Determination of WO 00/61729 8 PCT/USO0/09721 binding free energies for nucleic acid molecules is well-known in the art (see, e.g., Turner et al., 1987, CSH Symp. Quant. Biol. LII pp.123-133; Frier et al., 1986, Proc. Nat. Acad. Sci. USA 83:9373-9377; Turner et al., 1987, J. Am. Chem. Soc. 109:3783-3785. A percent complementarity indicates the percentage of contiguous 5 residues in a nucleic acid molecule which can form hydrogen bonds (e.g., Watson Crick base pairing) with a second nucleic acid sequence (e.g., 5, 6, 7, 8, 9, 10 out of 10 being 50%, 60%, 70%, 80%, 90%, and 100% complementary). "Perfectly complementary" means that all the contiguous residues of a nucleic acid sequence will hydrogen bond with the same number of contiguous residues in a second nucleic 10 acid sequence. In preferred embodiments of the present invention, inhibition of expression of repressor genes is related to treatment of a disease or conditions. By "related" is meant that the inhibition of repressor gene RNAs and thus reduction in the respective levels of protein activity will relieve to some extent the symptoms of the 15 disease or condition. In another preferred embodiment, the invention features nucleic acid based techniques (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or 20 inhibit the expression of genes capable of repressing interferon-alpha (IFN-a). Repressors of IFN-c include, but are not limited to, IRF-2 (Lopez et al., 1997, J. Biol Chem 272, 22788-22799). In another preferred embodiment, the invention features nucleic acid techniques (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic 25 acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of genes capable of repressing Granulocyte colony stimulating factor (G-CSF). These repressor genes include, but are not limited to, CCAAT displacement protein (CDP) (Khanna-Gupta et al, 1997, Blood 90, 2784 30 2795) and Genesis (Xu et al, 1998, Leukemia, 12, 207-2012).

WO 00/61729 9 PCTUSOO/09721 In another preferred embodiment, the invention features the use of enzymatic nucleic acids (e.g. ribozymes) that cleave the RNAs encoded by repressor genes capable of repressing erythropoietin (Epo) expression. The list of genes capable of inhibiting Epo include, but are not limited to, TR2 Orphan Receptor (Lee et al., The 5 Journal of Biological Chemistry, 271, 10405-10412), EAR3/COUP-TF-1 (Galson et al., 1995, Molecular and Cellular Biology, 15, 2135-2144), and GATA Transcription Factors (Imagawa et al., 1997, Blood, 89, 1430-1439). The inhibition of one or more of these repressing factors would increase cellular production of Epo which would be beneficial for applications including but not limited to: adjuvant 10 therapy for chemotherapy and treatment during renal dialysis. In preferred embodiments, the ribozymes of the present invention have binding arms that are complementary to the target sequences in Tables III-VII (i.e., Tables III, IV, V, VI, and VII). Examples of such ribozymes are also shown in Tables III-VIII. Table III displays target sequences and ribozymes targeting GATA 15 transcription factors (1,2,3,4,6). Table IV displays target sequences and ribozymes targeting TR2 & TR2-11 Orphan Receptors, table V displays target sequences and ribozymes for EAR3/COJP-TF-1, table VI displays target sequences and ribozymes for IRF-2, and table VII displays target sequences and ribozymes for CDP. Examples of such ribozymes consist essentially of sequences defined in these 20 Tables. In yet another embodiment, the invention features antisense nucleic acid molecules and 2-5A chimera including sequences complementary to the target sequences shown in tables III-VII. Such nucleic acid molecules can include sequences as shown for the binding arms of the ribozymes in Tables III-VII (i.e., the 25 left-most and right-most sequence portions in the columns headed "RZ." Similarly, triplex molecules can be provided targeted to the corresponding DNA target regions, and containing the DNA equivalent of a target sequence or a sequence complementary to the specified target (substrate) sequence. Typically, antisense molecules will be complementary to a target sequence along a single contiguous 30 sequence of the antisense molecule. However, in certain embodiments, an antisense molecule may bind to substrate such that the substrate molecule forms a loop, and/or WO 00/61729 10 PCT/US0O/09721 an antisense molecule may bind such that the antisense molecule forms a loop. Thus, the antisense molecule may be complementary to two (or even more) non contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule may be complementary to a target sequence or 5 both. By "consists essentially of' in connection with ribozyme sequences is meant that the active ribozyme contains an enzymatic center, or core, equivalent to those in the examples, and binding arms able to bind RNA such that cleavage at the target site occurs. Other sequences may be present which do not significantly interfere 10 with such cleavage. Thus, a core region may, for example, include one or more loop or stem-loop structures which do not prevent enzymatic activity. "X" in the sequences in Tables III-VII can be such a loop. Thus, in one aspect, the invention features ribozymes that inhibit repressor gene expression. These chemically or enzymatically synthesized ribozyme molecules 15 contain substrate binding domains that bind to accessible regions of their target RNAs. The ribozymes also contain domains that catalyze the cleavage of target RNA. The enzymatic nucleic acid molecules are preferably ribozymes of the hammerhead or hammerhead-like motif (Kore et al., 1998, Nucleic Acids Research 26, 4116-4120; Ludwig & Sproat, International PCT Publication No. WO 98/58058 20 ) or hairpin motif. Alternatively, the ribozymes are DNAzymes. Chemically synthesized ribozyme molecules also include ribozymes assembled together from various fragments of nucleic acid using a chemical or an enzymatic ligation method. Upon binding, the ribozymes cleave the target RNAs, preventing translation and protein accumulation. The expression of genes repressed by repressor genes 25 ("repressed genes") may be elevated in the absence of or under reduced level of repressor genes. This elevated level of the repressed gene may be beneficial to the cell and target organism. In a preferred embodiment, ribozymes are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells. The nucleic acid or nucleic acid complexes can be locally 30 administered to relevant tissues ex vivo, or in vivo through injection, infusion pump or stent, with or without their incorporation in biopolymers. In another preferred WO 00/61729 11 PCT/USOO/09721 embodiment, the ribozyme is administered to the site of TR2 Orphan Receptor, TR2-11 Orphan Receptor, EAR3/COUP-TF-1, and GATA transcription factors, CDP, or IRF-2 expression (e.g. liver cells, cancer cells) in an appropriate liposomal vehicle. 5 In another aspect of the invention, ribozymes that cleave target molecules and TR2 Orphan Receptor, TR2-11 Orphan Receptor, EAR3/COUP-TF-1, and GATA transcription factors, CDP, or IRF-2 activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme expressing viral vectors could be constructed 10 based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the ribozymes are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of ribozymes. Such vectors might be repeatedly administered as necessary. Once expressed, the ribozymes 15 cleave the target RNA. Delivery of ribozyme expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that would allow for introduction into the desired target cell (for a review see Couture and Stinchcomb, 1996, TIG., 12, 510). In another aspect of the 20 invention, ribozymes that cleave target molecules and inhibit cell proliferation are expressed from transcription units inserted into DNA, RNA, or viral vectors. Preferably, the recombinant vectors capable of expressing the ribozymes are locally delivered as described above, and transiently persist in smooth muscle cells. However, other mammalian cell vectors that direct the expression of RNA may be 25 used for this purpose. By "patient" is meant an organism which is a donor or recipient of explanted cells or the cells themselves. "Patient" also refers to an organism to which enzymatic nucleic acid molecules can be administered. Preferably, a patient is a mammal or mammalian cells. More preferably, a patient is a human or human cells. 30 By "vectors" is meant any nucleic acid- and/or viral-based technique used to deliver a desired nucleic acid.

WO 00/61729 12 PCT/USOO/09721 In another aspect, the nucleic acid molecule of the present invention is administered individually or in combination or in conjunction with other drugs, can be used to treat diseases or conditions. For example, to treat a disease or condition associated with cancer, the patient may be treated, or other appropriate cells may be 5 treated, as is evident to those skilled in the art. By "comprising" is meant including, but not limited to, whatever follows the word "comprising". Thus, use of the term "comprising" indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present. By "consisting of' is meant including, and limited to, whatever 10 follows the phrase "consisting of'. Thus, the phrase "consisting of' indicates that the listed elements are required or mandatory, and that no other elements may be present. By "consisting essentially of' is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the 15 phrase "consisting essentially of' indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they affect the activity or action of the listed elements. Other features and advantages of the invention will be apparent from the 20 following description of the preferred embodiments thereof, and from the claims. Description Of The Preferred Embodiments The drawings will first briefly be described. Figure 1 shows the secondary structure model for seven different classes of enzymatic nucleic acid molecules. Arrow indicates the site of cleavage. --------- indicate 25 the target sequence. Lines interspersed with dots are meant to indicate tertiary interactions. - is meant to indicate base-paired interaction. Group I Intron: P1-P9.0 represent various stem-loop structures (Cech et al., 1994, Nature Struc. Bio., 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 WO 00/61729 13 PCT/USOO/09721 means 5' splice site; 3'SS means 3'-splice site; IBS means intron binding site; EBS means exon binding site (Pyle et al., 1994, Biochemistry, 33, 2716). VS RNA: I-VI are meant to indicate six stem-loop structures; shaded regions are meant to indicate tertiary interaction (Collins, International PCT Publication No. WO 96/19577). HDV 5 Ribozyme: : I-IV are meant to indicate four stem-loop structures (Been et al., US Patent No. 5,625,047). Hammerhead Ribozyme: : I-III are meant to indicate three stem-loop structures; stems I-III can be of any length and may be symmetrical or asymmetrical (Usman et al., 1996, Curr. Op. Struct. Bio., 1, 527). Hairpin Ribozyme: Helix 1, 4 and 5 can be of any length; Helix 2 is between 3 and 8 base-pairs long; Y is a pyrimidine; Helix 10 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 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 - 20 base pairs) to stabilize the ribozyme structure, and preferably is a protein binding site. In each 15 instance, each N and N' independently is any normal or modified base and each dash represents a potential base-pairing interaction. These nucleotides may be modified at the sugar, base or phosphate. Complete base-pairing is not required in the helices, but is preferred. Helix 1 and 4 can be of any size (i.e., o and p is each independently from 0 to any number, e.g., 20) as long as some base-pairing is maintained. Essential bases are 20 shown as specific bases in the structure, but those in the art will recognize that one or more may be modified chemically (abasic, base, sugar and/or phosphate modifications) or replaced with another base without significant effect. Helix 4 can be formed from two separate molecules, i.e., without a connecting loop. The connecting loop when present may be a ribonucleotide with or without modifications to its base, sugar or phosphate. 25 "q" is 2 bases. The connecting loop can also be replaced with a non-nucleotide linker molecule. H refers to bases A, U, or C. Y refers to pyrimidine bases. " " refers to a covalent bond. (Burke et al., 1996, Nucleic Acids & Mol. Biol., 10, 129; Chowrira et al., US Patent No. 5,631,359). Figure 2 is an example of the secondary structure of a hammerhead ribozyme 30 targeting hGATA-2 which has the sequence contained in Seq. I.D. No. 281.

WO 00/61729 14 PCT/USOO/09721 Figure 3 is a schematic diagram indicating the mechanism of action by the nucleic acid molecules of the present invention. The regulation of transcription initiation can occur by one or more transcription factors working together. When more than one factor is involved the transcription factors can be present as 5 homodimers or heterodimers. In some cases, the formation of heterodimers would result in repression of transcription, while homodimers would form inactive transcription complexes. By blocking the expression of one subunit of the heterodimer, the equilibrium would shift towards formation of more homodimers resulting in a reduced formation of active repressors and enhanced transcription. 10 Figure 4 is a graph demonstrating increased erythropoietin synthesis in Hep3B cells following cobalt induction and administration of ribozymes targeting GATA transcription factor 2, TR2 orphan receptor and EAR3/COUP-TR1 compared to the irrelevant controls (IR1 and IR2). Figure 5 is a graph demonstrating increased erythropoietin synthesis in 15 Hep3B cells without cobalt induction and administration of ribozymes targeting GATA transcription factor 2, TR2 orphan receptor and EAR3/COUP-TR1 compared to the irrelevant controls (IR1 and IR2). Figure 6 is a bar graph demonstrating increased Epo expression compared to irrelevant controls in Hep3B cells following continuous delivery of ribozymes 20 targeting hGATA-2 transcription factor RNA. Figure 7 is a bar graph demonstrating increased Epo expression compared to irrelevant controls in Hep3B cells following continuous delivery of ribozymes targeting EAR3/Coup-TR1 RNA. Figure 8 is a bar graph demonstrating increased Epo expression compared to 25 irrelevant controls in Hep3B cells following pulsed delivery of ribozymes targeting hGATA-2 transcription factor RNA. Figure 9 is a bar graph demonstrating increased Epo expression compared to irrelevant controls in Hep3B cells following pulsed delivery of ribozymes targeting EAR3/Coup-TR1 RNA.

WO 00/61729 15 PCT/USOO/09721 Eukaryotic Gene Repression For the transcription of genes, a number of transcription factors are required for gene expression and its modulation. The most prevalent type of regulator genes within eukaryotes appear to be those that function to aid RNA polymerase in the 5 initiation of gene expression, however, many examples exist of genes under negative control. This important class of factors is known as negative regulators or repressors. These trans-acting protein factors (repressor proteins) generally modulate the rates of transcription by binding to a specific site on a gene. The binding site is typically a cis-element upstream to the target gene, often within the promoter and is in many 10 cases less than 10 nucleotides in length. Genes under negative control are those that are generally constitutively expressed unless turned off by repressor protein(s). In certain situations, the expression of repressed genes become highly desirable. Therefore stimulating the expression of repressed genes by inhibiting the expression of repressor genes would have a beneficial effect in treating a variety of 15 diseases. A number of proteins and/or peptides exist which would have such beneficial effects on cells or patients. Several non-limiting examples are described below. Those of ordinary skill in the art will recognize that other genes exist which an organism would benefit from their increased expression. Erythropoietin: Erythropoetin is a 30.4 kDA glycoprotein hormone which is 20 produced in the kidney and fetal liver as a response hypoxia (Galson et al., supra). The hormone regulates erythrocyte production and functions as a survival factor for the precursors of erythrocytes in bone marrow (Maxwell & Radcliffe, 1998, Curr. Opin. in Hematol. 5, 166-170). It is believed that a hemoglobin like sensor which is present within cells producing Epo, acts as a receptor for oxygen molecules 25 (Goldberg et al., 1988, Science 242, 1412-1415). When the level of oxygen falls below tightly regulated parameter, Erythropoietin synthesis is induced. A number of indications may be treated using Epo. For example, patients with renal disease may develop anemia which is defined as an absence of erythrocytes within blood. Treatment with recombinant Epo can significantly enhance the 30 production of these red blood cells (Maxwell & Radcliffe, supra). By inhibiting the WO 00/61729 16 PCTUSOO/09721 production of Epo repressors, the kidneys or liver and other parts of the body may be induced to synthesize erythropoietin to counter anemia. Another application of the present invention is as an adjuvant for chemotherapy. During chemotherapy, the patient may lose a large quantity of red blood cells. By inhibiting a repressor gene 5 for erythropoietin, the Epo protein could be expressed in elevated quantities in the kidneys or liver which would in turn stimulate the production of more erythrocytes. Granulocyte Colony Stimulating Factor (G-CSF): Granulocyte colony stimulating factor (G-CSF) is a hematopoietic growth factor that regulates the production and function of neutrophils from committed progenitor cells. It is 10 produced in vivo by monocytes, fibroblasts and endothelial cells. Recombinant G CSF is given clinically to decrease neutropenia associated with chemotherapy as well as treatment for congenital diseases such as severe chronic neutropenia . An alternative to exogenous addition of G-CSF would be to produce more endogenous G-CSF, thus potentially avoiding the limitations and complications associated with 15 injection of therapeutic proteins. There are several potential molecular targets that may act as indirect or direct repressors of G-CSF production or activity. CDP or CCAAT displacement protein is a known transcription repressor that binds to a negative regulatory element to block gene expression. It has extensive homology to the Drosophila cut protein. Reports indicate that CDP binds to the Lactoferrin gene 20 and suppresses basal promoter activity. Overexpression of CDP blocks G-CSF induced neutrophil maturation in cultured myeloid stem cells (Blood 90, 2784-95, 1997). Another potential target is Genesis, a transcriptional repressor which blocks granulocytic differentiation of myeloid cells (Leukemia 12, 207-212, 1998). Genesis is a member of the "winged-helix" transcription factor regulatory family. 32D 25 myeloid cells that are over-expressing Genesis fail to mature when stimulated with G-CSF. Genesis is expressed almost exclusively in embryonic stem cells and embryonal carcinoma cells. Both CDP and Genesis appear to be involved in the regulation of development and down-regulation of these could relieve a blockage in stem cell maturation. 30 Interferon-alpha: Interferon exhibits multiple biological effects through the induction of over 30 genes encoding proteins that have antiviral, antiproliferative, immunomodulatory and cytokine stimulation functions. Alpha interferon (IFN-A) is WO 00/61729 17 PCT/US0O/09721 a critical immune system modulator. IFN-A is encoded by a large family of structurally related genes. Interferon therapy is used for cell proliferation disorders (cancer) and viral infection (HBV, HCV). Interferon-alpha differential gene expression is accomplished by a complex interaction between cis-acting DNA 5 regulatory regions and the corresponding trans-acting factors. One potential limitation for expression of the interferon-alpha genes is the repressor transcription factor IRF-2 (JBC 272, 22788-99, 1997). There are also other negative regulatory regions for which the trans-acting repressors have not yet been identified, but which could be additional targets inhibition by nucleic acid molecules of the present 10 invention. Inhibiting expression of this transcriptional repressor could allow increased levels of endogenous interferon-alpha to be produced. There are also other negative regulatory regions for which the trans-acting repressors have not yet been identified, but which could be additional targets for inhibition by nucleic acid molecules of the present invention. An advantage of this approach would be the 15 avoidance of the production of antibodies to exogenous interferon as well as the avoidance of the autoimmune complications often seen with exogenous interferon alpha administration. Mechanism of action of Nucleic Acid Molecules of the Invention 20 Antisense: Antisense molecules may be modified or unmodified RNA, DNA, or mixed polymer oligonucleotides and primarily function by specifically binding to matching sequences resulting in inhibition of peptide synthesis (Wu-Pong, Nov 1994, BioPharm, 20-33). The antisense oligonucleotide binds to target RNA by Watson Crick base-pairing and blocks gene expression by preventing ribosomal 25 translation of the bound sequences either by steric blocking or by activating RNase H enzyme. Antisense molecules may also alter protein synthesis by interfering with RNA processing or transport from the nucleus into the cytoplasm (Mukhopadhyay & Roth, 1996, Crit. Rev. in Oncogenesis 7, 151-190). In addition, binding of single stranded DNA to RNA may result in nuclease 30 degradation of the heteroduplex (Wu-Pong, supra; Crooke, supra). To date, the only backbone modified DNA chemistry which will act as substrates for RNase H are WO 00/61729 18 PCTUSOO/09721 phosphorothioates and phosphorodithioates. Recently it has been reported that 2' arabino and 2'-fluoro arabino- containing oligos can also activate RNase H activity. A number of antisense molecules have been described that utilize novel configurations of chemically modified nucleotides, secondary structure, and/or 5 RNase H substrate domains (Woolf et al., International PCT Publication No. WO 98/13526; Thompson et al., USSN 60/082,404 which was filed on April 20, 1998; Hartmann et al., USSN 60/101,174 which was filed on September 21, 1998) all of these are incorporated by reference herein in their entirety. Triplex Forming Oligonucleotides (TFO): Single stranded DNA may be 10 designed to bind to genomic DNA in a sequence specific manner. TFOs are comprised of pyrimidine-rich oligonucleotides which bind DNA helices through Hoogsteen Base-pairing (Wu-Pong, supra)The resulting triple helix composed of the DNA sense, DNA antisense, and TFO disrupts RNA synthesis by RNA polymerase. The TFO mechanism may result in gene expression or cell death since binding may 15 be irreversible (Mukhopadhyay & Roth, supra) 2-5A Antisense Chimera: The 2-5A system is an interferon mediated mechanism for RNA degradation found in higher vertebrates (Mitra et al., 1996, Proc Nat Acad Sci USA 93, 6780-6785). Two types of enzymes, 2-5A synthetase and RNase L, are required for RNA cleavage. The 2-5A synthetases require double 20 stranded RNA to form 2'-5' oligoadenylates (2-5A). 2-5A then acts as an allosteric effector for utilizing RNase L which has the ability to cleave single stranded RNA. The ability to form 2-5A structures with double stranded RNA makes this system particularly useful for inhibition of viral replication. (2'-5') oligoadenylate structures may be covalently linked to antisense 25 molecules to form chimeric oligonucleotides capable of RNA cleavage (Torrence, supra). These molecules putatively bind and activate a 2-5A dependent RNase, the oligonucleotide/enzyme complex then binds to a target RNA molecule which can then be cleaved by the RNase enzyme. Enzymatic Nucleic Acid: Seven basic varieties of naturally-occurring 30 enzymatic RNAs are known presently. In addition, several in vitro selection (evolution) strategies (Orgel, 1979, Proc. R. Soc. London, B 205, 435) have been WO 00/61729 19 PCT/USOO/09721 used to evolve new nucleic acid catalysts capable of catalyzing cleavage and ligation of phosphodiester linkages (Joyce, 1989, Gene, 82, 83-87; Beaudry et al., 1992, Science 257, 635-641; Joyce, 1992, Scientific American 267, 90-97; Breaker et al., 1994, TIBTECH 12, 268; Bartel et al.,1993, Science 261:1411-1418; Szostak, 1993, 5 TIBS 17, 89-93; Kumar et al., 1995, FASEB J., 9, 1183; Breaker, 1996, Curr. Op. Biotech., 7, 442; Santoro et al., 1997, Proc. Natl. Acad. Sci., 94, 4262; Tang et al., 1997, RNA 3, 914; Nakamaye & Eckstein, 1994, supra; Long & Uhlenbeck, 1994, supra; Ishizaka et al., 1995, supra; Vaish et al., 1997, Biochemistry 36, 6495; all of these are incorporated by reference herein). Each can catalyze a series of reactions 10 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 RNA. Such binding occurs through the target binding portion of an enzymatic nucleic acid which is held in close proximity to an 15 enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has 20 bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets. The enzymatic nature of a ribozyme has significant advantages, such as the concentration of ribozyme necessary to affect a therapeutic treatment is lower. This advantage reflects the ability of the ribozyme to act enzymatically. Thus, a single 25 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 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 30 ribozyme.

WO 00/61729 20 PCT/USOO/09721 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 efficient cleavage achieved in vitro (Zaug et al., 324, 5 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; 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 10 as therapeutic agents for human disease (Usman & McSwiggen, 1995 Ann. Rep. Med. Chem. 30, 285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38, 2023 2037). Ribozymes can be designed to cleave specific RNA targets within the background of cellular RNA. Such a cleavage event renders the RNA non functional and abrogates protein expression from that RNA. In this manner, 15 synthesis of a protein associated with a disease state can be selectively inhibited. Synthesis of Nucleic acid Molecules Synthesis of nucleic acids greater than 100 nucleotides in length is difficult using automated methods, and the therapeutic cost of such molecules is prohibitive. In this invention, small nucleic acid motifs ("small refers to nucleic acid motifs no 20 more than 100 nucleotides in length, preferably no more than 80 nucleotides in length, and most preferably no more than 50 nucleotides in length; e.g., antisense oligonucleotides, hammerhead or the hairpin ribozymes) are preferably used for exogenous delivery. The simple structure of these molecules increases the ability of the nucleic acid to invade targeted regions of RNA structure. Exemplary molecules 25 of the instant invention were chemically synthesized, and others can similarly be synthesized. Oligodeoxyribonucleotides were synthesized using standard protocols as described in Caruthers et al., 1992, Methods in Enzymology 211,3-19, and is incorporated by reference. The method of synthesis used for normal RNA including certain 30 enzymatic nucleic acid molecules follows the procedure as described in Usman et WO 00/61729 21 PCT/USO0/09721 al., 1987 J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990 Nucleic Acids Res., 18, 5433; and Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684 and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. In a non-limiting example, small 5 scale syntheses were conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 pmol scale protocol with a 7.75 min coupling step for alkylsilyl protected nucleotides and a 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. Alternatively, syntheses at the 0.2 imol scale can be done on a 96-well plate 10 synthesizer, such as the instrument produced by Protogene (Palo Alto, CA) with minimal modification to the cycle. A 15-fold excess (31 gL of 0.1 M = 3.1 pmol) of phosphoramidite and a 38.7-fold excess of S-ethyl tetrazole (31 pL of 0.25 M = 7.75 pmol) relative to polymer-bound 5'-hydroxyl was used in each coupling cycle. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, 15 determined by colorimetric quantitation of the trityl fractions, were 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer; detritylation solution was 3% TCA in methylene chloride (ABI); capping was performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); oxidation solution was 16.9 mM 12, 49 20 mM pyridine, 9% water in THF (PERSEPTIVE

TM

). Burdick & Jackson Synthesis Grade acetonitrile was used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) was made up from the solid obtained from American International Chemical, Inc. Deprotection of the RNA was performed using either a two-pot or one-pot 25 protocol. For the two-pot protocol, the polymer-bound trityl-on oligoribonucleotide was transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65 'C for 10 min. After cooling to -20 'C, the supernatant was removed from the polymer support. The support was washed three times with 1.0 mL of EtOH:MeCN:H20/3:1:1, vortexed and the supernatant was 30 then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, were dried to a white powder. The base deprotected oligoribonucleotide was resuspended in anhydrous TEA/HF/NMP solution (300 pL WO 00/61729 22 PCT/USOO/09721 of a solution of 1.5 mL N-methylpyrrolidinone, 750 ptL TEA and 1 mL TEA-3HF to provide a 1.4 M HF concentration) and heated to 65 'C. After 1.5 h, the oligomer was quenched with 1.5 M NH 4

HCO

3 . Alternatively, for the one-pot protocol, the polymer-bound trityl-on 5 oligoribonucleotide was transferred to a 4 mL glass screw top vial and suspended in a solution of 33% ethanolic methylamine/DMSO:1/1 (0.8 mL) at 65 'C for 15 min. The vial was brought to r.t. TEA-3HF (0.1 mL) was added and the vial was heated at 65 'C for 15 min. The sample was cooled at -20 'C and then quenched with 1.5 M

NH

4

HCO

3 10 For purification of the trityl-on oligomers, the quenched NH 4

HCO

3 solution was loaded onto a C-18 containing cartridge that had been prewashed with acetonitrile followed by 50 mM TEAA. After washing the loaded cartridge with water, the RNA was detritylated with 0.5% TFA for 13 min. The cartridge was then washed again with water, salt exchanged with 1 M NaCl and washed with water 15 again. The oligonucleotide was then eluted with 30% acetonitrile. Inactive hammerhead ribozymes or binding attenuated control (BAC) oligonucleotides) 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). The average stepwise coupling yields were >98% (Wincott et al., 1995 20 Nucleic Acids Res. 23, 2677-2684). Those of ordinary skill in the art will recognize that the scale of synthesis can be adapted to be larger or smaller than the example described above including but not limited to 96 well format, all that is important is the ratio of chemicals used in the reaction. Alternatively, the nucleic acid molecules of the present invention can 25 be synthesized separately and joined together by ligation (Moore et al., 1992, Science 256, 9923; Draper et al., International PCT publication No. WO 93/23569; Shabarova et al., 1991, Nucleic Acids Research 19, 4247) Administration of Nucleic Acid Molecules WO 00/61729 23 PCT/USOO/09721 Methods for the delivery of nucleic acid molecules is described in Akhtar et al., 1992, Trends Cell Bio., 2, 139; and Delivery Strategies for Antisense Oligonucleotide Therapeutics, ed. Akhtar, 1995 which are both incorporated herein by reference. Sullivan et al., PCT WO 94/02595, further describes the general methods for delivery of 5 enzymatic RNA molecules . These protocols may be utilized for the delivery of virtually any nucleic acid molecule. Nucleic acid molecules may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive 10 microspheres. For some indications, nucleic acid molecules may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the nucleic acid/vehicle combination is locally delivered by direct injection or by use of a catheter, infusion pump or stent. Other routes of delivery include, but are not limited to, intravascular, intramuscular, subcutaneous or joint injection, aerosol inhalation, oral 15 (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery. More detailed descriptions of nucleic acid 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 pharmaceutical agents. 20 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 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 25 composition. When it is desired to use a liposome delivery mechanism, standard protocols for 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 the like. 30 The present invention also includes pharmaceutically acceptable formulations of the compounds described. These formulations include salts of the above WO 00/61729 24 PCT/USOO/09721 compounds, e.g., acid addition salts, for example, salts of hydrochloric, hydrobromic, acetic acid, and benzene sulfonic acid. A pharmacological composition or formulation refers to a composition or formulation in a form suitable for administration, e.g., systemic administration, into 5 a cell or patient, preferably a human. Suitable forms, in part, depend upon the use or the route of entry, for example oral, transdermal, or by injection. Such forms should not prevent the composition or formulation to reach a target cell (i.e., a cell to which the negatively charged polymer is desired to be delivered to). For example, pharmacological compositions injected into the blood stream should be soluble. 10 Other factors are known in the art, and include considerations such as toxicity and forms which prevent the composition or formulation from exerting its effect. By "systemic administration" is meant in vivo systemic absorption or accumulation of drugs in the blood stream followed by distribution throughout the entire body. Administration routes which lead to systemic absorption include, 15 without limitations: intravenous, subcutaneous, intraperitoneal, inhalation, oral, intrapulmonary and intramuscular. Each of these administration routes expose the desired negatively charged polymers, e.g., nucleic acids, to an accessible diseased tissue. The rate of entry of a drug into the circulation has been shown to be a function of molecular weight or size. The use of a liposome or other drug carrier 20 comprising the compounds of the instant invention can potentially localize the drug, for example, in certain tissue types, such as the tissues of the reticular endothelial system (RES). A liposome formulation which can facilitate the association of drug with the surface of cells, such as, lymphocytes and macrophages is also useful. This approach may provide enhanced delivery of the drug to target cells by taking 25 advantage of the specificity of macrophage and lymphocyte immune recognition of abnormal cells, such as the cancer cells. The invention also features the use of a composition comprising surface modified liposomes containing poly (ethylene glycol) lipids (PEG-modified, or long circulating liposomes or stealth liposomes). These formulations offer an method for 30 increasing the accumulation of drugs in target tissues. This class of drug carriers resists opsonization and elimination by the mononuclear phagocytic system (MPS or WO 00/61729 25 PCT/USOO/09721 RES), thereby enabling longer blood circulation times and enhanced tissue exposure for the encapsulated drug (Lasic et al. Chem. Rev. 1995, 95, 2601-2627; Ishiwata et al., Chem. Pharm. Bull. 1995, 43, 1005-1011). Such liposomes have been shown to accumulate selectively in tumors, presumably by extravasation and capture in the 5 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 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; 10 Choi et al., International PCT Publication No. WO 96/10391; Ansell et al., International PCT Publication No. WO 96/10390; Holland et al., International PCT Publication No. WO 96/10392; all of these are incorporated by reference herein). Long-circulating liposomes are also likely to protect drugs from nuclease degradation to a greater extent compared to cationic liposomes, based on their ability 15 to avoid accumulation in metabolically aggressive MPS tissues such as the liver and spleen. All of these references are incorporated by reference herein. The present invention also includes compositions prepared for storage or administration which include a pharmaceutically effective amount of the desired compounds in a pharmaceutically acceptable carrier or diluent. Acceptable carriers 20 or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A.R. Gennaro edit. 1985) hereby incorporated by reference herein. For example, preservatives, stabilizers, dyes and flavoring agents may be provided. Id. at 1449. These include sodium benzoate, sorbic acid and esters ofp-hydroxybenzoic 25 acid. In addition, antioxidants and suspending agents may be used. Id. A pharmaceutically effective dose is that dose required to prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) of a disease state. The pharmaceutically effective dose depends on the type of disease, the composition used, the route of administration, the type of 30 mammal being treated, the physical characteristics of the specific mammal under consideration, concurrent medication, and other factors which those skilled in the WO 00/61729 26 PCT/USOO/09721 medical arts will recognize. Generally, an amount between 0.1 mg/kg and 100 mg/kg body weight/day of active ingredients is administered dependent upon potency of the negatively charged polymer. The nucleic acid molecules of the present invention may also be administered 5 to a patient in combination with other therapeutic compounds to increase the overall therapeutic effect. The use of multiple compounds to treat an indication may increase the beneficial effects while reducing the presence of side effects. Alternatively, the nucleic acid molecules of the instant invention (e.g. ribozyme and antisense molecules) can be expressed within cells from eukaryotic 10 promoters (e.g., Izant and Weintraub, 1985 Science 229, 345; McGarry and Lindquist, 1986 Proc. Natl. Acad. Sci. USA 83, 399; Scanlon et al., 1991, Proc. Nati. Acad. Sci. USA, 88, 10591-5; Kashani-Sabet et al., 1992 Antisense Res. Dev., 2, 3-15; Dropulic et al., 1992 J. Virol, 66, 1432-41; Weerasinghe et al., 1991 J Virol, 65, 5531-4; Ojwang et al., 1992 Proc. Natl. Acad. Sci. USA 89, 10802-6; 15 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; Good et al., 1997, Gene Therapy, 4, 45; all of the references are hereby incorporated in their totality by reference herein). Those skilled in the art realize that any nucleic acid can be expressed in eukaryotic cells from the appropriate DNA/RNA vector. The activity 20 of such nucleic acids can be augmented by their release from the primary transcript by a ribozyme (Draper et al., PCT WO 93/23569, and Sullivan et al., PCT WO 94/02595; Ohkawa et al., 1992 Nucleic Acids Symp. Ser., 27, 15-6; Taira et al., 1991, Nucleic Acids Res., 19, 5125-30; Ventura et al., 1993 Nucleic Acids Res., 21, 3249-55; Chowrira et al., 1994 J. Biol. Chem. 269, 25856; all of the references are 25 hereby incorporated in their totality by reference herein). In another aspect of the invention, enzymatic nucleic acid molecules that cleave target molecules are expressed from transcription units (see for example Couture et al., 1996, TIG., 12, 510) inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme 30 expressing viral vectors could be constructed based on, but not limited to, adeno associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant WO 00/61729 27 PCT/USOO/09721 vectors capable of expressing the ribozymes are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of ribozymes. Such vectors might be repeatedly administered as necessary. Once expressed, the ribozymes cleave the target RNA. The active 5 ribozyme contains an enzymatic center or core equivalent to those in the examples, and binding arms able to bind target nucleic acid molecules such that cleavage at the target site occurs. Other sequences may be present which do not interfere with such cleavage. Delivery of ribozyme expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex 10 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 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 molecules (ribozyme, 15 antisense) of the instant invention is disclosed. The nucleic acid sequence encoding the nucleic acid molecule of the instant invention is operably linked in a manner which allows expression of that nucleic acid molecule. In another aspect the invention features, the expression vector comprises: a transcription initiation region (e.g., eukaryotic pol I, II or III initiation region); b) a 20 transcription termination region (e.g., eukaryotic pol I, II or III termination region); c) a gene encoding at least one of the nucleic acid molecule of the 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 25 (ORF) for a protein operably linked on the 5' side or the 3'-side of the gene encoding the nucleic acid molecule of the invention; and/or an intron (intervening sequences). Transcription of the ribozyme or antisense sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol III promoters will be 30 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, WO 00/61729 28 PCT/USOO/09721 silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters are also used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990 Proc. Natl. Acad. Sci. U S A, 87, 6743-7; Gao and Huang 1993 Nucleic Acids Res., 21, 2867-72; Lieber et al., 1993 5 Methods Enzymol., 217, 47-66; Zhou et al., 1990 Mol. Cell. Biol., 10, 4529-37). Several investigators have demonstrated that ribozymes expressed from such promoters can function in mammalian cells (e.g. Kashani-Sabet et al., 1992 Antisense Res. Dev., 2, 3-15; Ojwang et al., 1992 Proc. Natl. Acad. Sci. U S A, 89, 10802-6; Chen et al., 1992 Nucleic Acids Res., 20, 4581-9; Yu et al., 1993 Proc. 10 Natl. Acad. Sci. U S A, 90, 6340-4; L'Huillier et al., 1992 EMBO J 11, 4411-8; Lisziewicz et al., 1993 Proc. Natl. Acad. Sci. U. S. A., 90, 8000-4; Thompson et al., 1995 Nucleic Acids Res. 23, 2259; Sullenger & Cech, 1993, Science, 262, 1566). More specifically, transcription units such as the ones derived from genes encoding U6 small nuclear (snRNA), transfer RNA (tRNA) and adenovirus VA RNA are 15 useful in generating high concentrations of desired RNA molecules such as ribozymes in cells (Thompson et al., supra; Couture and Stinchcomb, 1996, supra; Noonberg et al., 1994, Nucleic Acid Res., 22, 2830; Noonberg et al., US Patent No. 5,624,803; Good et al., 1997, Gene Ther. 4, 45; Beigelman et al., International PCT Publication No. WO 96/18736; all of these publications are incorporated by 20 reference herein. The above transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated virus vectors), or viral RNA vectors (such as retroviral or alphavirus vectors) (for a review see Couture and Stinchcomb, 1996, supra). 25 In yet another aspect the invention features an expression vector comprising nucleic acid sequence encoding at least one of the nucleic acid molecule of the invention, in a manner which allows expression of that nucleic acid molecule. The expression vector comprises in one embodiment; a) a transcription initiation region; b) a transcription termination region; c) a gene encoding at least one said nucleic 30 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 acid molecule. In another preferred embodiment the expression vector WO 00/61729 29 PCT/USOO/09721 comprises: a) a transcription initiation region; b) a transcription termination region; c) an open reading frame; d) a gene encoding at least one said nucleic acid molecule, wherein said gene is operably linked to the 3'-end of said open reading frame; and wherein said gene is operably linked to said initiation region, said open reading 5 frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In yet another embodiment the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) a gene encoding at least one said nucleic acid molecule; and wherein said gene is operably linked to said initiation region, said intron and said 10 termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In another embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) an open reading frame; e) a gene encoding at least one said nucleic acid molecule, wherein said gene is operably linked to the 3'-end of said open reading frame; and 15 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 expression and/or delivery of said nucleic acid molecule. In another aspect, the invention features a method of increasing the level of target protein in a cell comprising the step of contacting the cell with nucleic acid 20 molecules capable of specifically inhibiting the expression of a repressor protein that represses the expression of the target protein under conditions suitable for increasing the level of target protein in the cell. In another aspect, this invention features a method of increasing the level of target protein in a cell comprising the step of isolating cells from a patient, 25 introducing the nucleic acid molecule (synthetic or vector) capable of inhibiting the expression of a repressor of target protein, introducing the cells into same or a different patient under conditions for the increased expression of the target protein. Optimizing Ribozyme Activity Catalytic activity of the ribozymes described in the instant invention can be 30 optimized as described by Draper et al., supra. The details will not be repeated here, WO 00/61729 30 PCT/USOO/09721 but include altering the length of the ribozyme binding arms, or chemically synthesizing ribozymes with modifications (base, sugar and/or phosphate) that prevent their degradation by serum ribonucleases and/or enhance their enzymatic activity (see e.g., Eckstein et al., International Publication No. WO 92/07065; 5 Perrault et al., 1990 Nature 344, 565; Pieken et al., 1991 Science 253, 314; Usman and Cedergren, 1992 Trends in Biochem. Sci. 17, 334; Usman et al., International Publication No. WO 93/15187; and Rossi et al., International Publication No. WO 91/03162; Sproat, US Patent No. 5,334,711; and Burgin et al., supra; all of these describe various chemical modifications that can be made to the base, 10 phosphate and/or sugar moieties of enzymatic RNA molecules). Modifications which enhance their efficacy in cells, and removal of bases from stem loop structures to shorten RNA synthesis times and reduce chemical requirements are desired. (All these publications are hereby incorporated by reference herein). There are several examples in the art describing sugar, base and phosphate 15 modifications that can be introduced into enzymatic nucleic acid molecules without significantly effecting catalysis and with significant enhancement in their nuclease stability and efficacy. Ribozymes are modified to enhance stability and/or enhance catalytic activity by modification with nuclease resistant groups, for example, 2' amino, 2'-C-allyl, 2'-fluoro, 2'-O-methyl, 2'-H, nucleotide base modifications (for a 20 review see Usman and Cedergren, 1992 TIBS 17, 34; Usman et al., 1994 Nucleic Acids Symp. Ser. 31, 163; Burgin et al., 1996 Biochemistry 35, 14090). Sugar modification of enzymatic nucleic acid molecules have been extensively described in the art (see Eckstein et al., International Publication PCT No. WO 92/07065; Perrault et al. Nature 1990, 344, 565-568; Pieken et al. Science 1991, 253, 314 25 317; 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 by reference herein). Such publications describe general methods and strategies to determine the location of 30 incorporation of sugar, base and/or phosphate modifications and the like into ribozymes without inhibiting catalysis, and are incorporated by reference herein. In WO 00/61729 31 PCT/US00/09721 view of such teachings, similar modifications can be used as described herein to modify the nucleic acid catalysts of the instant invention. Nucleic acid catalysts having chemical modifications which maintain or enhance enzymatic activity are provided. Such nucleic acid is also generally more 5 resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. As exemplified herein such ribozymes are useful in a cell and/or in vivo even if activity over all is reduced 10 fold (Burgin et al., 1996, Biochemistry, 35, 14090). Such ribozymes herein are said to "maintain" the enzymatic activity on all RNA ribozyme. 10 Therapeutic ribozymes delivered exogenously must optimally be stable within cells until translation of the target RNA has been inhibited long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, ribozymes must be resistant to nucleases in order to function as effective intracellular therapeutic agents. 15 Improvements in the chemical synthesis of RNA (Wincott et al., 1995 Nucleic Acids Res. 23, 2677; incorporated by reference herein) have expanded the ability to modify ribozymes by introducing nucleotide modifications to enhance their nuclease stability as described above. By "enhanced enzymatic activity" is meant to include activity measured in 20 cells and/or in vivo where the activity is a reflection of both catalytic activity and ribozyme stability. In this invention, the product of these properties is increased or not significantly (less that 10 fold) decreased in vivo compared to an all RNA ribozyme. In yet another preferred embodiment, nucleic acid catalysts having chemical 25 modifications which maintain or enhance enzymatic activity is provided. Such nucleic acid is also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. As exemplified herein such ribozymes are useful in a cell and/or in vivo even if activity over all is reduced 10 fold (Burgin et al., 1996, Biochemistry, 35, 14090). Such 30 ribozymes herein are said to "maintain" the enzymatic activity on all RNA ribozyme.

WO 00/61729 32 PCT/USOO/09721 Use of these molecules will lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple ribozymes targeted to different genes, ribozymes coupled with known small molecule inhibitors, or intermittent treatment with combinations of ribozymes (including 5 different ribozyme motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules may also include combinations of different types of nucleic acid molecules. Therapies may be devised which include a mixture of ribozymes (including different ribozyme motifs), antisense and/or 2-5A chimera molecules to one or more targets to alleviate symptoms of a disease. 10 Animal Models In order to evaluate the therapeutic potential nucleic acid targeting repressors of Epo synthesis, two animals models of chronic anemia exist. These models are: 1) chemotherapy-induced anemia in mice and 2.) chronic renal failure-induced anemia in mice. Both of these murine models closely mimic the pathophysiology of the 15 corresponding disease in human patients. (1) Chemotherapy-Induced Anemia in C57/B16 Mice: The primary goal of these studies is to evaluate the effectiveness of nucleic acid therapy targeted at increasing the body's ability to produce red blood cells and thus counteract 20 chemotherapy-induced severe anemia. Many drugs used to treat cancer patients (cytotoxic compounds) adversely effect the bone marrow and markedly reduce the number of circulating red blood cells. This is primarily due to a decrease in the hormone erythropoietin (Epo) which stimulates the production of red blood cells. Many types of chemotherapy also 25 induce hemolytic anemia. The severe anemia that occurs with many forms of chemotherapy has a marked impact on the patients' quality of life (exercising, performing job duties, etc.) and normal daily activities are difficult to perform. Nucleic acid molecules targeting repressors of Epo are evaluated for their ability to improve severe loss of circulating red blood cells (anemia) associated with 30 chemotherapy in C57Bl/6 mice which is an indication of enhanced Epo production.

WO 00/61729 33 PCT/USOO/09721 Experimental Procedure: All studies are performed on pathogen-free, 20 25g female C57B1/6 mice. Mice are housed in a pathogen-free environment and allowed food and water ad lib. For induction of anemia, all animals receive an intraperitoneal injection of 3.5 mg/kg Cisplatin (CDDP), in a 200 pL volume (Day 5 0). For all blood sample collection, animals are euthanized by CO 2 asphyxiation. Baseline blood samples are obtained via cardiac puncture for hematological and biochemical analyses prior to initiating chemotherapy (Day-0). Blood samples obtained via cardiac puncture, body weights and spleen weights from groups of 10 10 CDDP-treated animals are obtained beginning on Day-I and three times weekly for 27 days. Acute renal failure with marked uremia (elevation of BUN) and anemia is apparent within 1 day post-single dose chemotherapy. Hematocrits are measured, in triplicate, using a Clay Adams microhematocrit centrifuge on a pooled whole blood sample (in EDTA) from each group of 10 animals at each termination. In addition, a 15 complete blood cell count is obtained from whole blood. The remaining sample is spun down and plasma samples are saved at -70'C for later determination of plasma erythropoietin levels. Plasma Epo levels A determined by a commercially available ELISA (R&D Systems, Minneapolis, MN) using the manufacturer's protocol. 20 Compound Efficacy Studies Four groups of animals are tested per drug: Group 1 receives active nucleic acid molecules (e.g. ribozyme), Group 2 receives scrambled attenuated control nucleic acid molecules as therapy and Group 3 receives vehicle as therapy. Group 4 serves as a positive therapeutic control and receives recombinant human erythropoietin (rhu-Epo; 2500 U/kg, thrice weekly). There are 10 animals 25 per group per time point and up to three doses of nucleic acid molecules per group for groups 1 and 2. There are 13 time points (Days 0, 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26) in each study. Ten animals per group per time point per dose are euthanized and blood samples collected and tested as described above. Test agents may be delivered via an ALZETTM osmotic pump (Alza Scientific Products) 30 subcutaneously or intravenously, subcutaneous bolus, direct i.p. injection or intravenously via the tail vein.

WO 00/61729 34 PCT/US0O/09721 (2) Chronic Renal Failure-Induced Anemia in C57/B6 Mice (Zhang et al., 1996, Nephron 72: 654-661): The primary goal of these studies is to evaluate the effectiveness of nucleic acid therapy targeted at increasing the body's ability to produce red blood cells and thus counteract chronic renal failure-induced severe 5 anemia. Chronic renal failure (CRF) is a functional clinical diagnosis characterized by a progressive and irreversible decline in the kidneys' ability to filter the blood (glomerular filtration rate; GFR). This condition is associated with a number a primary diseases including, but not limited to, glomerulonephritis, cardiovascular 10 disease and hypertension, diabetes, kidney infections and urinary tract disease. CRF afflicts more than 370,000 patients in the U.S. alone. Most of these patients' disease will progress to end stage renal disease (ESRD) and will require renal replacement therapy (hemodialysis, peritoneal dialysis, kidney transplant) to survive. Both the loss of functional kidney tissue and the dialysis procedure cause a severe reduction 15 in the red blood cell count of these patients. This primarily due to a decrease in the hormone erythropoietin (Epo) which stimulates the production of red blood cells. The severe chronic anemia has a marked impact on the patients' quality of life (exercising, performing job duties, etc.) and normal daily activities are difficult to perform. 20 Experimental Procedure: All studies are performed on pathogen-free, female 20-25g C57B1/6. Mice are housed in a pathogen-free environment and allowed food and water ad lib. To establish CRF in these animals, two surgical procedures are required separated by a two week recovery period. For the first surgical procedure, animals are anesthetized with a ketamine/ 25 xylazine cocktail (1.2 mg/kg and .14 mg/kg) and a right lateral laparotomy is performed. The entire surface of the right kidney, excluding a 2 mm rim around the hilum, is electrocoagulated using a disposable vasectomy cautery (2250'F). The kidney is returned to the renal fossa and wounds are aseptically closed with 4-0 silk suture and surgical clips Animals are allowed to recover for two weeks before the 30 second surgical procedure is performed. For the second procedure, animals are anesthetized with a ketamine/ xylazine cocktail (1.2 mg/kg and .14 mg/kg) and a left lateral laparotomy is performed. The left kidney is removed and the wound WO 00/61729 35 PCT/USOO/09721 aseptically closed with 4-0 silk suture. All animals receive penicillin G (Durapen 30,000 U, IM) following each surgical procedure. For all blood sample collections, animals are euthanized by CO 2 asphyxiation. Blood samples, body weights and spleen weights are obtained from 5 groups of 8 animals each weekly beginning at week 1 post-second surgery for evaluation of disease progression up until week 14 post-Nx. A group of 8 normal animals are euthanized and blood samples obtained for control hematology and biochemistry determinations. Therefore, there are 12 euthanization time points including the control group. From reports in the literature, CRF with marked uremia 10 (persistent elevation of BUN) and anemia will be present within 8 weeks post-Nx. At necropsy, blood samples will be obtained via cardiac puncture for clinical chemistry (BUN and creatinine) and hematology (WBC, Diff., platelet count) tests are performed by an external laboratory (IDEXX, Inc.). Compound Efficacy Studies: There are four groups of animals per drug 15 tested: Group 1 receives active nucleic acid molecules of the invention (e.g. ribozyme), Group 2 receives scrambled attenuated nucleic acid as therapy and Group 3 receives vehicle as therapy. Group 4 serves as a positive therapeutic control and receives recombinant human erythropoietin (rhu-Epo; 250 U/kg; thrice weekly). There are 8 animals per group and up to three doses of nucleic acid per group for 20 groups 1 and 2. Test agents may be delivered via an ALZETTM osmotic pump (Alza Scientific Products) subcutaneously or intravenously, subcutaneous bolus, direct i.p. injection or intravenously via the tail vein. 25 (3) Chemotherapy-Induced Myelosuppression in C57/B16 Mice (Misaki et al., 1998, British Journal of Cancer 77:884-889) : The primary goal of these studies is to evaluate the effectiveness of therapy targeted at increasing the body's ability to produce white blood cells and thus counteract chemotherapy-induced neutropenia. The ability of these nucleic acid molecules to improve severe loss of 30 circulating white blood cells (neutropenia) associated with chemotherapy in Balb/c mice is tested . A protocol modified from that of Misaki, et al. (1998) is utilized.

WO 00/61729 36 PCT/USOO/09721 Experimental Procedure: All studies are performed on pathogen-free, 25-30g female Balb/c mice. Mice are housed in a pathogen-free environment and allowed food and water ad lib. For induction of myelosuppression, all animals receive an intraperitoneal injection of 200 mg/kg Cyclophosphamide (CPA), in a 200 ptL 5 volume (Day-0). There are 16 time points for blood sampling. Samples are obtained to evaluate plasma G-CSF levels and CBCs. A single vehicle control group and a rhuG-CSF group is used for all ribozyme formulation testing protocols. Body and spleen weights are recorded. 10 For all blood sample collections, animals are euthanized by CO 2 asphyxiation. Baseline blood samples are obtained via cardiac puncture for hematological analyses prior to initiating chemotherapy (Day-0). One group of ten animals is euthanized pre- CPA, 4 days post-CPA( at 6am, at 12 noon and at 6pm) and daily thereafter. Two mls of whole blood is sent to IDEXX veterinary laboratory 15 for a complete blood cell count. The remaining samples are spun down and plasma samples are saved at -70'C for later determination of plasma G-CSF levels. Plasma G-CSF levels are determined in-house by a commercially available ELISA. Remaining plasma samples are frozen for future analyses. Compound Efficacy Studies: There are four groups of animals per drug 20 tested: Group 1 receives active nucleic acid molecules of the invention (e.g. ribozyme), Group 2 receives scrambled attenuated nucleic acid as therapy and Group 3 receives vehicle as therapy. Group 4 serves as a positive therapeutic control and receives recombinant human rhu-G-CSF (5 jig/kg, daily). There are 10 animals per group per time point and up to three doses of ribozyme per group for groups 1 and 2. 25 On day 0 animals receive cyclophosphamide (CPA; 200 mg/kg, IP). On day 4, nucleic acid therapy is initiated. Therapy is continued daily until Day 16. There are 16 time points (Days 0-17) in each study. Ten animals per group per time point per dose are euthanized and blood samples collected. One group of ten animals is euthanized pre- CPA, 4 days post-CPA, at 6 and at 12 hrs. after nucleic acid dosing 30 and daily thereafter. Two mls of whole blood are sent to IDEXX veterinary laboratory for a complete blood cell count. The remaining sample is spun down and plasma samples are saved at -70"C for later determination of plasma erythropoietin WO 00/61729 37 PCT/US0O/09721 levels. Plasma G-CSF levels is determined in-house by a commercially available ELISA. Remaining plasma samples are frozen for future analyses. Test agents may be delivered via an ALZETTM osmotic pump (Alza Scientific Products) subcutaneously or intravenously, subcutaneous bolus, direct i.p. injection or 5 intravenously via the tail vein. (4) Chronic, Relapsing Experimental Autoimmune Encephalitis in Rats: Multiple sclerosis is a disorder of unknown cause that has a number of symptoms (weakness, numbness, lack of coordination, headaches) which are caused by 10 destruction of the protective tissue (myelin) surrounding the spinal cord. Many studies have been published which support both a possible immune system problem and/or an infectious agent. It is a chronic debilitating disease with a clinical course from onset to death of approximately 35 years. There are no spontaneous animal models of MS but an autoimmune disorder which resembles MS can be induced in 15 rodents. This is accomplished by either injection under the skin of a crude brain mixture or purified proteins obtained from the brain. The goal of this model is to evaluate the effectiveness of therapy with nucleic acid targeted against the interferon-_ repressor in improving the symptoms with this disease in an animal model. 20 Experimental Procedure: All studies are performed on pathogen-free, male Dark Agouti (DA) rats 7-9 weeks of age obtained from Harlan, Inc. Rats are housed in a pathogen-free environment and allowed food and water ad lib for one week prior to initiation of the study. All animals are immunized with syngeneic spinal cord (SSC) in incomplete Freund's adjuvant (IFA). For the preparation of the spinal 25 cord emulsion, cords from donor DA rats are removed and minced thoroughly. One part spinal cord to one part IFA (v/W) is used to prepare emulsion. The appropriate dose of emulsion is determined in the pilot study. 0.2 ml of homogenate (SSC and IFA) is injected into the dorsal base of the tail root on day 0. All animals receive 75 mg/kg of syngeneic spinal cord. The primary endpoint of these studies is a clinical 30 score. The clinical scoring system is as follows: 0.0 = Normal WO 00/61729 38 PCT/USOO/09721 0.5 = Partial loss of tail tone 1.0 = Complete loss of tail tone 2.0 = Hindlimb weakness or dragging one hindlimb 3.0 = Paralysis of both hindlimbs 5 4.0 = Paralysis of both hindlimbs and weakness in forelimbs 5.0 = Moribund Histopathologic evidence of demyelination is a secondary endpoint. Clinical scores and body weights are determined daily for 21 days and EOD thereafter until 10 day 90. At the termination of this study (90 days post-immunization), animals are euthanized. At necropsy, brain and spinal cord are removed, fixed in 10% buffered formalin and submitted for histopathologic analyses. The experimental method (dose of SSC) which provides the greatest reproducibility and the pathophysiology that most closely mimics the human clinical disease is then chosen for use in the 15 compound efficacy studies. Compound Efficacy Studies: This study evaluates the efficacy of nucleic acid molecules targeted against the interferon-alpha repressor gene on severity of clinical score and on histopathological changes in the spinal cord and brain of these animals. There are two main groups of animals per drug tested: one prophylactic treatment 20 (beginning three days post-immunization) and one therapeutic treatment (following the first paralytic episode- at approximately day 15 post-immunization). Each main group has four subgroups: Group 1 receives vehicle as therapy, Group 2 receives scrambled attenuated nucleic acid control as therapy, Group 3 receives active nucleic acid (e.g. ribozyme) and Group 4 receives recombinant human interferon-a (8 M.U., 25 SC, per animal, EOD for 90 days). Nucleic acid molecules are administered at 30 mg/kg, EOD, SC for 90 days. There are 10 animals per subgroup and up to three doses per subgroup for dose/response studies. Test agents may be delivered via an ALZETTM osmotic pump (Alza Scientific Products) subcutaneously or intravenously, subcutaneous bolus, direct i.p. 30 injection or intravenously via the tail vein. (6) B16 melanoma in C57/B16 Mice (Nishimura et al., 1985, Clin Exp Metastasis 3, 295-304): The primary goal of these studies is to evaluate the WO 00/61729 39 PCT/USOO/09721 effectiveness of nucleic acid therapy targeted increasing the body's ability to produce interferon-alpha and thus augment the immune response and inhibit cell proliferation. Two syngeneic melanoma cell lines, B16/B16 and B16/F10, are utilized. 5 Experimental Procedure: All studies are performed on pathogen-free, 25 30g female C57/B16 mice. Mice are housed in a pathogen-free environment and allowed food and water ad lib. B16/B16: On Day 0, animals are injected with B16/B16 cells (5x10 5 ), SC in 100 pl normal saline, mid-dorsal, in the scapular region. Primary tumor volume are 10 measured using microcalipers. triplicate length and width measurements are obtained from each tumor three days per week. Tumor volumes are calculated from tumor length and width measurements according to the equation: Tumor volume = 0.5ab 2 where a=longest axis of the tumor 15 b=shortest axis of the tumor In one set of animals (Group I), primary tumors are allowed to grow for up to 25 days. Therapeutic endpoints in this group are primary tumor volume, metastases and survival. In the second set of animals (Group II), once B16BL6 tumor growth reaches 500 mm 3 , the primary tumors are removed. Therapeutic endpoints in this 20 group are metastases and survival. Metastatic growth in the lungs is observed at death or at day 25 (final day of experiment). Metastasis is observed in the lungs at the end of the experiment by weighing the lungs and by counting the macrometastases under 25X magnification. If no macrometastases are present, the lungs are perfusion fixed in formalin for subsequent sectioning and histological 25 examination of micrometastases and survival time is recorded. Compound Efficacy Studies: There are four subgroups of animals for Groups I and II per drug tested: Subgroup A receives active nucleic acid molecules of the present invention, Subgroup B receives scrambled attenuated nucleic acid control as therapy, and Subgroup C receives vehicle as therapy. Subgroup D serves as a 30 positive therapeutic control and receives recombinant human IFN-alpha A/D (8 M.U., SC, per animal, EOD for 30 days). There are 15 animals per group and up to three doses of nucleic acid per group for groups A and B. Therapy begins on day-3 WO 00/61729 40 PCT/USOO/09721 and is continued daily until Day 25. At necropsy, blood samples are obtained via cardiac puncture, spun down and plasma samples are saved at -70C for future analyses. Test agents may be delivered via an ALZETTM osmotic pump (Alza 5 Scientific Products) subcutaneously or intravenously, subcutaneous bolus, direct i.p. injection or intravenously via the tail vein. B16/F10: On Day 0, animals are injected with B16/F10 (5x10 4 ) IV in 100 pl normal saline. Therapeutic endpoints in this group are metastases and survival. Metastatic growth in the lungs is observed at death or at day 25 (final day of 10 experiment). Metastasis is observed in the lungs at the end of the experiment by weighing the lungs and by counting the macrometastases under 25X magnification. If no macrometastases are present the lungs are perfusion fixed in formalin for subsequent sectioning and histological examination of micrometastases and survival time is recorded. 15 Compound Efficacy Studies: There are four groups of animals per drug tested: Group 1 receives active nucleic acid molecules (e.g. ribozymes), Group 2 receives scrambled attenuated nucleic acid control as therapy, and Group 3 receivesvehicle as therapy. Group 4 serves as a positive therapeutic control and receives recombinant human IFN-alpha A/D (8 M.U., SC, per animal, EOD for 30 days). There are 15 20 animals per group and up to three doses of nucleic acid molecules per group for groups 1 and 2. Therapy begins on day-3 and is continued daily until Day 25. At necropsy, blood samples are obtained via cardiac puncture, spun down and plasma samples are saved at -70 0 C for future analyses. Test agents may be delivered via an ALZETTM osmotic pump (Alza 25 Scientific Products) subcutaneously or intravenously, subcutaneous bolus, direct i.p. injection or intravenously via the tail vein. (7) Colorectal Carcinoma (COLON-26) in Balb/c Mice (Sanada et al., 1990, Acta Med Okayama 44, 217-222, Ramani et al., 1989, Int J Cancer 43, 140-146, 30 1989): The primary goal of these studies is to evaluate the effectiveness of nucleic acid therapy targeted increasing the body's ability to produce interferon-alpha and thus augment the immune response and inhibit cell proliferation.The study evaluates WO 00/61729 41 PCT/USOO/09721 nucleic acid molecules targeting repressors of IFN-alpha on their ability to improve survival and reduce metastases in Balb/c mice with COLON-26 carcinoma. Experimental Procedure: All studies are performed on pathogen-free, 18-20g female Balb/c mice. Mice are housed in a pathogen-free environment and allowed food and 5 water ad lib. On Day 0, animals are injected with COLON-26 cells (1x10 6 ) in 100 pl normal saline into the splenic capsule. On day-5 following tumor cell inoculation, the primary tumors are removed. Therapeutic endpoints are metastases and survival. Metastatic growth in the lungs and in the liver is observed at death or at day 40 (final day of experiment). 10 Metastasis is observed in the lungs and liver at the end of the experiment by weighing the organs and by counting the macrometastases under 25X magnification. If no macrometastases are present in these tissues, the organs are perfusion fixed in formalin for subsequent sectioning and histological examination of micrometastases and survival time is recorded. 15 Compound Efficacy Studies There are four groups of animals per drug tested: Group 1 receives active nucleic acid molecules of the invention (e.g.ribozymes), Group 2 receives scrambled attenuated nucleic acid control as therapy, and Group 3 receives vehicle as therapy. Group 4 serves as a positive therapeutic control and receives recombinant human IFN-alpha A/D (8 M.U., SC, per animal, EOD for 30 20 days). There are 15 animals per group and up to three doses of nucleic acid molecules per group for groups 1 and 2. Therapy begins on day-3 and is continued daily until Day 40. At necropsy, blood samples are obtained via cardiac puncture, spun down and plasma samples are saved at -70C for future analyses. Test agents may be delivered via an ALZETTM osmotic pump (Alza Scientific 25 Products) subcutaneously or intravenously, subcutaneous bolus, direct i.p. injection or intravenously via the tail vein. Examples The following are non-limiting examples showing the selection, isolation, 30 synthesis and activity of enzymatic nucleic acids of the instant invention. The following examples demonstrate the selection of ribozymes that cleave TR2 Orphan Receptor, EAR3/COUP-TF-1, GATA transcription factors, IRF-2, WO 00/61729 42 PCT/US0O/09721 Genesis, and CDP. The methods described herein represent a scheme by which ribozymes may be derived that cleave other RNA targets expressed from repressor genes. Those of ordinary skill in the art will recognize that other ribozymes with motifs other than hammerhead may also be devised in a similar fashion and are 5 within the scope of the invention. Example 1: Identification of Potential Ribozyme Cleavage Sites in GATA Transcription Factor 2 (hGATA-2) The sequences of human GATA transcription factor 2 (HUMGATA2A, Genbank Accession No. M77810 (Dorfman et al., 1997, J. Biol. Chem, 267, 1279 10 1285) were screened for accessible sites using a computer folding algorithm. Regions of the RNA that did not form secondary folding structures and contained potential hammerhead cleavage sites were identified. The sequences of these cleavage sites are shown in Table III. Example 2: Selection of Ribozyme Cleavage Sites in Human GATA transcription 15 factor To test whether the sites predicted by the computer-based RNA folding algorithm corresponded to accessible sites in GATA transcription factor, 70 hammerhead sites were selected for analysis. Ribozyme target sites were chosen by analyzing genomic sequences of hGATA-2 (Dorfman, supra) and prioritizing the 20 sites on the basis of folding. Hammerhead ribozymes were designed that could bind each target (see Figure 1) and were individually analyzed by computer folding (Christoffersen et al., 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al., 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable 25 intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA. An example of a ribozyme targeted to hGATA-2 is shown in figure 2.

WO 00/61729 43 PCT/USOO/09721 Example 3: Chemical Synthesis and Purification of Ribozymes for Efficient Cleavage of GATA Transcription Factor 2 RNA Ribozymes of the hammerhead and/or hammerhead like motifs were designed to anneal to various sites in the RNA message. The binding arms are 5 complementary to the target site sequences described above. The ribozymes were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described in Usman et al., (1987 J. Am. Chem. Soc., 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as 10 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 U for G5 and a U for A14 (numbering from Hertel et al., 1992 Nucleic Acids Res., 20, 3252). Hairpin ribozymes are synthesized in two parts and annealed to reconstruct the active 15 ribozyme (Chowrira and Burke, 1992 Nucleic Acids Res., 20, 2835-2840). Ribozymes are also 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'-fluoro, 2'-O-methyl, 2'-H (for a review see 20 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 reference) and were resuspended in water. The sequences of the chemically synthesized ribozymes used in this study are shown below in Table 25 III-VI. Example 4: Ribozyme Cleavage of hGATA-2 RNA Target in vitro Ribozymes targeted to the human hGATA-2 RNA are 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 30 nucleotide location within the hGATA-2 mRNA are given in Table III.

WO 00/61729 44 PCT/USOO/09721 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- 32 p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification. 5 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-HCl, pH 7.5 at 37 0 C, 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 10 cleavage buffer. As an initial screen, assays are carried out for 1 hour at 37 0 C using a final concentration of either 40 nM or 1 mM ribozyme, i.e., ribozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% xylene cyanol after which the sample is heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing 15 polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph of the gel. The percentage of cleavage is determined by PHOSPHOR IMAGER@ quantitation of bands representing the intact substrate and the cleavage products. Example 5: Increased Expression of Erythropoietin by Inhibition of Repressors of 20 Erythropoietin Transcriptional repressors of the erythropoetin gene were targeted with ribozymes in order to increase Epo levels. Ribozymes were synthesized targeting hGATA-2, TR-2, and EAR3/Coup-TF1. Ribozyme screening was performed by complexing with lipid, delivering to the appropriate cell line, and monitoring for Epo 25 production. The ability of these ribozymes to increase Epo expression in both induced (with CoCl 2 ) and non-induced cells was also tested. Erythropoietin (Epo) is produced in the adult kidney and fetal liver in response to hypoxia and CoCl 2 . Two human hepatoma cell lines, Hep G2 and Hep 3B, exhibit regulated expression of Epo in response to hypoxia and CoCl 2 . Ribozymes were tested under non-induced 30 and induced conditions to determine if Epo levels could be increased under one or both conditions.

WO 00/61729 45 PCT/US00/09721 Hep3B cells were plated at 1.8 x 10 4 cells per well in a 96 well plate. Ribozymes were then transfected into cells using cationic lipids 24 hours after seeding the plates. Two concentrations of each ribozyme (100 and 400 nm) were tested using 5 or 7.5 pig/ml of cationic lipid. The sequences for the ribozymes and 5 the irrelevant controls (IRI & IR2) are given in table VIII. Cells were then induced to express Erythropoietin by applying cell culture media containing CoCl 2 (50 nM). After 24 hours, 100 ml of media was removed from the plate well and added into a plate for an ELISA assay. The remaining media is aspirated off and the cells were frozen at -70"C until tested by CYQUANT T M assay using the manufacturer's 10 protocol. The ELISA for quantification of erythropoietin was performed using QUANTIKINE IVD T M kit sold by R&D Systems (Minneapolis, MN) by using the manufacturers protocol. The data indicates that a number of ribozymes were able to cause elevated expression of Epo in these cells compared to the inactive controls. Results are shown in Figures 4 and 5 for cobalt-induced and without cobalt 15 induction respectively. Example 6: Elevated Expression of Erythropoietin Over Time Using Ribozymes Targeting Epo Repressors Hep3B cells were prepared as described in example 5. Ribozymes (RPI No. 14260 20 (targeting hGATA-2) & 144521 (targeting EAR3/COUP-TR1; table VIII) at a concentration of 1 00nm were transfected into Hep3B cells using 5 pLg/ml of cationic lipid. Epo expression in these cells was measured at 36 and 48 hours for continuous delivery and at 12, 24, and 36 hours for pulsed delivery using an ELISA assay from example 5. The data was compared to two irrelevant and an untreated control (Unt) . 25 The sequences for the ribozymes and the irrelevant controls (IR-1 & IR-2) are given in table VIII. The ribozyme was either delivered continuously during the incubation period or added for just 4 hours and then replaced with fresh media (pulsed delivery). The data is shown in figures 6-9 which demonstrate that either continuous or pulsed delivery of ribozymes targeting hGATA-2 or EAR3/Coup-TR1 will result 30 in elevated expression of Epo in Hep3B cells compared to irrelevant and untreated controls.

WO 00/61729 46 PCT/USO0/09721 Diagnostic uses Nucleic acid molecules of this invention may be used as diagnostic tools to examine genetic drift and mutations within diseased cells or to detect the presence of specific RNA in a cell. For instance, the close relationship between ribozyme 5 activity and the structure of the target RNA allows the detection of mutations in any region of the molecule which alters the base-pairing and three-dimensional structure of the target RNA. By using multiple ribozymes described in this invention, one may map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with ribozymes may 10 be used to inhibit gene expression and define the role (essentially) of specified gene products in the progression of disease. In this manner, other genetic targets may be defined as important mediators of the disease. Other in vitro uses of ribozymes of this invention are well known in the art, and include detection of the presence of mRNAs associated with related conditions. Such RNA is detected by determining 15 the presence of a cleavage product after treatment with a ribozyme using standard methodology. In a specific example, ribozymes which can cleave 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 20 to identify mutant RNA in the sample. As reaction controls, synthetic substrates of 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 size markers for the analysis of wild-type and mutant 25 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 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 30 gain insight into the expression of mutant RNAs and putative risk of the desired phenotypic changes in target cells. The expression of mRNA whose protein product WO 00/61729 47 PCT/USOO/09721 is implicated in the development of the phenotype is adequate to establish risk. If probes of comparable specific activity are used for both 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 5 higher risk whether RNA levels are compared qualitatively or quantitatively. Additional Uses Potential usefulness of sequence-specific enzymatic nucleic acid molecules of the instant invention might have many of the same applications for the study of RNA that DNA restriction endonucleases have for the study of DNA (Nathans et al., 10 1975 Ann. Rev. Biochem. 44:273). For example, the pattern of restriction fragments could be used to establish sequence relationships between two related RNAs, and large RNAs could be specifically cleaved to fragments of a size more useful for study. The ability to engineer sequence specificity of the ribozyme is ideal for cleavage of RNAs of unknown sequence. 15 The nucleic acid molecules of the present invention may also be used for small and large scale synthesis of proteins. Nucleic acids such as enzymatic nucleic acids and antisense molecules may be administered into cells in culture to initiate in vitro synthesis of such repressed proteins as erythropoietin, G-CSF, or interferon alpha. The method involves the steps of contacting or introducing into a cell a 20 nucleic acid molecule (e.g. ribozyme or antisense) capable of down-regulating (inhibition) expression of a repressor protein which represses the expression of a target protein (repressed protein), such that the level of repressor protein will be decreased, resulting in the stimulation of expression of target protein in the cell. The target protein can then be purified from the cells using standard techniques known in 25 the art. Those of ordinary skill in the art will recognize that the method could also be utilized for the increase expression of other repressed proteins in addition to the proteins mentioned above. The inhibition of expression of repressor transcription factors using nucleic acids may also be utilized in non-human organisms. Particularly since negative 30 regulation of genes has been demonstrated in plants (Preston et al., 1998, J WO 00/61729 48 PCTIUSOO/09721 Bacteriol. 180, 4532-4537). For example, plants and fungi may have repressor transcription factors which, when inhibited, would allow for the increased expression of beneficial proteins for increased crop yield, disease resistance, and increases in synthesis for desired amino acids, oils, and the like. Ladner & Bird, 5 International Publication No. W08806601 describe the suppression of genes to inhibit the proliferation of viruses. Applicant describes the use of nucleic acid molecules to down-regulate gene expression of repressors in bacterial, microbial, fungal, viral, and eukaryotic systems including plant, or mammalian cells. All patents and publications mentioned in the specification are indicative of 10 the levels of skill of those skilled in the art to which the invention pertains. All references cited in this disclosure are incorporated by reference to the same extent as if each reference had been incorporated by reference in its entirety individually. One skilled in the art would readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, 15 as well as those inherent therein. The methods and compositions described herein as presently representative of preferred embodiments are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art, which are encompassed within the spirit of the invention, are defined by the scope of the claims. 20 It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. Thus, such additional embodiments are within the scope of the present invention and the following claims. The invention illustratively described herein suitably may be practiced in the 25 absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms "comprising", "consisting essentially of' and "consisting of' may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no 30 intention that in the use of such terms and expressions of excluding any equivalents WO 00/61729 49 PCT/USOO/09721 of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments, optional features, modification and variation of 5 the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the description and the appended claims. In addition, where features or aspects of the invention are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will 10 recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group or other group. Thus, additional embodiments are within the scope of the invention and within the following claims WO 00/61729 PCT/USO0/09721 50 TABLE I Characteristics of naturally occurring ribozymes Group I Introns e Size: -150 to >1000 nucleotides. e Requires a U in the target sequence immediately 5' of the cleavage site. - Binds 4-6 nucleotides at the 5-side of the cleavage site. e Reaction mechanism: attack by the 3'-OH of guanosine to generate cleavage products with 3'-OH and 5'-guanosine. e Additional protein cofactors required in some cases to help folding and maintainance of the active structure. - Over 300 known members of this class. Found as an intervening sequence in Tetrahymena thermophila rRNA, fungal mitochondria, chloroplasts, phage T4, blue-green algae, and others. * Major structural features largely established through phylogenetic comparisons, mutagenesis, and biochemical studies [',"]. * Complete kinetic framework established for one ribozyme (i,,'' e Studies of ribozyme folding and substrate docking underway [''sl. e Chemical modification investigation of important residues well established [xxi]. e The small (4-6 nt) binding site may make this ribozyme too non-specific for targeted RNA cleavage, however, the Tetrahymena group I intron has been used to repair a "defective" p-galactosidase message by the ligation of new p-galactosidase sequences onto the defective message [xuJ. RNAse P RNA (M1 RNA) " Size: -290 to 400 nucleotides. e RNA portion of a ubiquitous ribonucleoprotein enzyme. * Cleaves tRNA precursors to form mature tRNA ["Hi. e Reaction mechanism: possible attack by M -OH to generate cleavage products with 3' OH and 5'-phosphate. e 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 therapeutic applications is possible through hybridization of an External Guide Sequence (EGS) to the target RNA [xiv,") - Important phosphate and 2' OH contacts recently identified ["I" Group 11 Introns * -Size: >1000 nucleotides. e Trans cleavage of target RNAs recently demonstrated [XV"Ixx].

WO 00/61729 PCT/USOO/09721 Table 1 51 e Sequence requirements not fully determined. * Reaction mechanism: 2'-OH of an internal adenosine generates cleavage products with 3' OH and a "lariat" RNA containing a 3'-5' and a 2'-5' branch point. * Only natural ribozyme with demonstrated participation in DNA cleavage [","I] in addition to RNA cleavage and ligation. * Major structural features largely established through phylogenetic comparisons ["X]. - Important 2' OH contacts beginning to be identified ("IU] e Kinetic framework under development ["x'] Neurospora VS RNA * Size: -144 nucleotides. - Trans cleavage of hairpin target RNAs recently demonstrated ["']. - 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. e Binding sites and structural requirements not fully determined. e Only 1 known member of this class. Found in Neurospora VS RNA. Hammerhead Ribozyme .(see text for references) e Size: -13 to 40 nucleotides. e Requires the target sequence UH immediately 5' of the cleavage site. e Binds a variable number nucleotides on both sides of the cleavage site. 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. - 14 known members of this class. Found in a number of plant pathogens (virusoids) that use RNA as the infectious agent. - Essential structural features largely defined, including 2 crystal structures ["'" a Minimal ligation activity demonstrated (for engineering through in vitro selection) ["'I'] " Complete kinetic framework established for two or more ribozymes ["L]. - Chemical modification investigation of important residues well established ['"]. Hairpin Ribozyme e Size: -50 nucleotides. 0 Requires the target sequence GUC immediately 3' of the cleavage site. e Binds 4-6 nucleotides at the 5'-side of the cleavage site and a variable number to the 3 side of the cleavage site. a Reaction mechanism: attack by 2'-OH 5' to the scissile bond to generate cleavage products with 2',3'-cyclic phosphate and 5'-OH ends. e 3 known members of this class. Found in three plant pathogen (satellite RNAs of the tobacco ringspot virus, arabis mosaic virus and chicory yellow mottle virus) which uses RNA as the infectious agent. - Essential structural features largely defined [x""",II] WO 00/61729 PCT/USOO/09721 52 e Ligation activity (in addition to cleavage activity) makes ribozyme amenable to engineering through in vitro selection [""..] * Complete kinetic framework established for one ribozyme [xxxvi] e Chemical modification investigation of important residues begun {"".,'x''"]. Hepatitis Delta Virus (HDV) Ribozyme - Size: -60 nucleotides. - Trans cleavage of target RNAs demonstrated ['''']. * Binding sites and structural requirements not fully determined, although no sequences 5' of cleavage site are required. Folded ribozyme contains a pseudoknot structure [1]. " Reaction mechanism: attack by 2'-OH 5' to the scissile bond to generate cleavage products with 2',3'-cyclic phosphate and 5'-OH ends. " Only 2 known members of this class. Found in human HDV. * Circular form of HDV is active and shows increased nuclease stability [x] i . Michel, Francois; Westhof, Eric. Slippery substrates. Nat. Struct. Biol. (1994), 1(1), 5-7. Lisacek, Frederique; Diaz, Yolande; Michel, Francois. Automatic identification of group I intron cores in genomic DNA sequences. J. Mol. Biol. (1994), 235(4), 1206-17. "'. Herschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by.the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. Biochemistry (1990), 29(44), 10159-71. I'. 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. VI . 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. V" . 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. ix. 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. 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. Xi. Strobel, Scott A.; Cech, Thomas R.. Exocyclic Amine of the Conserved G.cntdot..I 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. Xi"i. Robertson, H.D.; Altman, S.; Smith, J.D. J. Biol. Chem., 24, 5243-5251 (1972). 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 WO 00/61729 PCT/US00/09721 53 ribozyme RNase P RNA. RNA (1995), 1(2), 210-18. ""i. 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. . 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. "X. 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. "". 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. "V. 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. "" . 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. ". 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. ""*v. 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. "" . 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 WO 00/61729 PCT/USOO/09721 54 (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. . 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. i. 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 00/61729 PCT/USOO/09721 55 Table II: 0.2 smol RNA Synthesis Cycle Reagents Equivalents Amounts (gL) Wait time (sec) Phosphoramidites 15- 31 465 SET 38.7 31 465 Acetic anhydride 655 124 5 N-methyl-imidazole 1245 124 5 TCA 700 732 10 Iodine 20.6 244 15 * Wait time does not include contact time during delivery.

WO 00/61729 PCT/USOO/09721 56 Table 121. H-ammrerhead ribozymes targeting GATA Transcription factors (1, 2, 3, 4, and 6) and the complementary Sequences POO Target Seg. RZSeq. Sbstrate I.D. bb I.D. th 37 1SEW CUCAG= CUGAUGAG X CGAA A~rCA 1697 CtI= C ACAC1G3 48 _______ 2 GLInn ctXPM.trG X CGAA AGUCG 1698 AC7GAzr T GOCACATC 56 HSEFM 3 OQxUt CfLr-A1rA X CCPA -ALILMM 1699 'TGCACT C CAi3 76 HSERYFI 4 UOGUU303 CtKPtr-AG X 03A AJ33= 1700 C3AAc= C C3AA 96 HSMYM 5 U333AUUJ CU3-ALP X OMA ACCU=l 1701 GCrCCAr T AA1TttCC 917 HSERYF1 6 CtGOn CUGAUGAG X CGAA AACCU33 1702 CCCA=i A AMICCA 100 HSEfFG 7 cc-=23 CMfLMG X CCAA AIL= 1703 AGGrAAr C CtCAGA 11 HSERMF 8 ACUtCALM CtXIflG X CMA ADGCC=f 1704 ~CAGAG C CAG 120 HERY1 9 GCClGG CtXAUCPG X CMA AaECAM 1705 CASIGr T CC~r 121 HSERF1 10 AGC CLr13)AG X COA AACECCAU 1706 A'IOIT C CC~IIO 135 HSEF1 21 UCCCCIM CUMUAG X CtPA ACtttCA2 1707 =0331r C CC~T033 147 HSERF1 12 G333=~i CUGIfl= X CMA AGGDC 1708 G333T C AGAGtt 157 H-CF1 13 AACX 3 aX2AMT3 X CGA AG3fl 1709 CAW=t' C CCOCrr 165 H.EFm 14 G*IXECACtX2mIfl- X x :A AC303 1710 CttCar T TG0= 166 HSRM 15 c3AI=~ CM~AUXG X CMA AAU 1711 CCCCr T GIGG=t 173 HSERF 16 CAAGA CM40A X CGA AUCttCA 1712 TLI=~ C cIacr !M 179. H.SFi. 17 GOCA CUGAUGAG X C3AA PGMGW 1713 AM=~I~ C GI= 186 H.EF1T 18 GUM= CGLr- X COA ACCCG 1714 i~TCTG r C CItCCA 189 HSTOM 19 CLXnX CULIGAX X OMA AGCC 1725 GGIG=w C CAAC 201 H.SfF1 20 AA)Lttt CtX fl x a3A NLLJCU 1716 ACAGAA C AGOG= 208 H.SL'FJ 21 G3AA CUGAIXG X CGAA PAC .CUG 1717 IAG= T TICI= 209. HSEFM 22 G30AC CUGUXIW X CMA ACC= 1718 CAGO= T TriTT= 210 HSEMMF 23 A03SA CMfl4IM X CA AA LU 1719 AGrrr T CrTIC 211 HSEfF1 24 GAGGOA C LIAG X CMA AAAA= 1720 G330= C ~I 213 HSE1 25 CAA CMMAG X COAA AGAAAC 1721 0i3rI= T CWOtI= 214 HSERF1 26 CCGG CUPLUJA1G X 03A AAGAAAC 1722 G7rr=1 C CCIC 219 HSE1 27 CA3 CLIGAMW~ X CGA AGO~k3 1723 ai'tCr C 'I3i= 234 HNERM 28 CGAxz LIGL7M X~t CM ~AGOMt 1724 TGG T G~T 248 HSERF1 29 A~tM CUMflG X CMA AXn= 1725 CAC T CCIUc 249 1HfER1 30 CAUGA CUMUG X 03A AGC= 1726 AGCAT C CIIG 252 HSERY1 31 G3I3 CUGAUMG X CMA AGM 1727 AGri= C CAM 297 HSEF' 32 CLt U= CLGUA X 03A AGO 1728 ACTGr A CICA3 300 HSERF1 33 CGtrn CaXPLa X COA AGPN= 1729 G~c A CP3A 318 HSRM 34 AfLocu axmomG X COA AGO 1730 'GG= A ~CAGCT 327 HSERF1 35 AGC CUMMA X OGA AGL0UCM 1731 ~CrG C CT 334 HSERM 36 ACJAm arGALU X CGA ACU333 1732 'TCCGI'0 C TIIA~ 336 HSEPM 37 ACAMM xLAU X OA AGMO 1733 CCIt'r T ICAG 337 RSE1 38 tUCtf CUCAMA X CMA AAGAMOGl 1734 COG=I T CAW 338 HSUMF 39 GUC=CKGUA CA AAL'Tf 1735 CAIt~rrr C AG7I 345 HSEEM 40___ GCAALnG xM X OM CCCL~ 1736 'iCAGr A CCCTIOC 351 HSM:CM 41 ALIAcaxwxmo X CMA AU33LZPC 1737 GIC T cGIAr 355 1HSERF1 42 AM=~J CflUtMG X COA AOCAU 1738 CM'I'I C AACT1=.

WO 00/61729 PCTUSOO/09721 57 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2. 3, 4. and 6) and the complementary sequences 362 RSRM 43 CCtCC G)U G X 02A ACAGUUPL 1739 ICAL'AIU GGAA3M 3-73 HSERF1 44 CCCCt33 MOfA1J3A X OW. AECJ 1740 GAC43OT C CAG= 384 HSEi'F 45 aum=~ capmlAG x a~m AGOC 1741 AGL33X'r C ACAAT 390 HSERYF1 46 ?GO= CtflMLA3 X 03A AU33=~' 1742 CIC A TGC 405 HSERFI 47 tLXtfC aAUGx X CCA AGGIXCtG 1743 cDi r A C3GA 421 HSEF1 48 GCXAO CUPMAX3 03AA ?AC= 1744 AcT)r C TACCG 423 HSEFM 49 .AGGCAG CUflAIXG X CCPA AGG 1745 G033C= A CCCI= 432 HSEF1 50 ACAAGU CfALA X 03A AG3MDf 1746 CtCI=r C AA.CIITG 443 HSEF1 51 (C03 CUCALMGL X CMA PACAA 1747 CI1I3IUT C CAC= 459 HSERYF1 52 G03AG CUGAMAGP X COA PLGLtfl 1748 CGG= C ITCT= 461 H-SRFI 53 atxn.A mw wt, x cmA Ao 1749 AGit-r C C7CCCCA 464 HSM:Z1. 54 '- CUAnMt X CGA AG%&O 1750 ALITC= C CtCAG 482 HSE1 55 UCCAUCC CtYAP X CCIA AUEU 1751 TWAAA C TGGA= 507 HSER'F1 56 UCLC=rD CUA~ri. X COA AGCUX 1752 CA rA T CCTGOA 508 HSERF1 57 mrc mm=~D x CA AAM 1753 ACCAr C CISAC 5,18 HSEF 58 cuGA~tG x~t Km ~AGLUttX 1754 TGAA T TGAGD 519 HSERF1 59 aUGxr CUPOU X CMA AAt IE .1755 GPLACIT T GAAGACAG 547 HSF1 60 ?xE7;S cmkumG~ x 0:A AGGYCfLM 1756 CCAtT C CrGAT 572 HSE1F1 61 GAGU= CULM X CSA MOM= 1757 ~CICI' T CATC= 573 HSRF cX62f 03 ciaX X CGAA AGO= 1758 ACI~IT C AITC'I 576 HSEMM 63 mam ammw. x cmA Amv=) 1759 GCr=. C AC7ttCI 580 H5EEGM 64 GG; CUGAUGA X CMA 1AG.XI 1760 TCTC~ C CCITI= 586 HSERFI 65 amuom cumumG x 03A ACAML 1761 aICiCr C CCCA7A 593 HSE 66 ALMAG= C DZL X 03P AIMt1M 1762 MTCCAM' A G027= 599 NSmfF1 67 GtttCfl C)ALCA X OMA AGCCUJ 1763 ATPDI= T AGO= 600 HSEfFO 68 GOC CGAUGA X CGA AAGCXUA 1764 ThGIIr A T003= 615 HSEFI 69 UACtL3M CDL7AX~ K A AG0XA=E 1765 CCCIGCr T TItCA 616 HSERF1 70 mmcmm CtxmaI x 03A AAGLX~r- 1766 CCICIT T TCIAG1AC 617 HSEF1 71 GrfLM CUAIX~ K 7 AAALXIW3 1767 C7GCIT T CCG 618 HSEeF 72 Amx wommXK x CmA AAAAGUCi 1768 IGACIrrr C CA7 623 HSEM1 73 MAA 33A CLIGAGA x a2A ACU'03%A 1769 'TtC= A Crl=rr 627 HSRF 74 GAGAAAG~ aX;GA X 0:A AGGUfl 1770 CAG7I'~ T crrriti 628 HSERF1 75 GL&A A C!xaum x CmA AADGU 1771 AGMCC C TrI'ICI 630 HSM;M. 76 U03GAGA CLGUA XXP 03AA 1ALAN3O 1772 1AC1Ir T TIIC= 631 HSEM 77 GLX~i CUGAUGA X CMA AG~aJ 1773 ACCrICI T TIrC 632 HSERY1 78 Gx3.m axum K CM AAAA 1774 CtCltI= T CICI 633 HSERF1 79 CGL13 CtLIGAGA X CGA AAAAGW 1775 crcrr= c TCCA 635 HSRYP1 80 CLC3UO CUCLUAG X 0A AGAAA~ 1776 ~T~rr C CAC33 652 HSG1F1 91 aa~mAu ct~x~oL x CGA A0333U 1777 AttWI' C AATUM 656 HSERFI 82__ Goa= axUA X A AULUXM 1778 CCICAAT T CACG .657 HS ~1 83 AGO=UI CGAUGA X CA AALXCPM 1779 Ct"ICAATr C AOA 666 HSE'F1 84 G4ZA aCOUGX~ K A AGO== 1780 AGCr A TIttC'I 668 HSERYL 85______ L CDCAUGA X MiA AMU=f 1781 [0=IAT T CCICI 669 HSE~nM 86 uoom atmmw x amA mmr=~ 1782 1 G= C CMMI= WO 00/61729 PCT/USOO/09721 58 Table IU. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences {672 HSERF1. 87 *OC2fLXXX CW.3AG X CCA AOAAM 1783 CrA'rI= C 'ICCCAG 674 RSCM1 88 AAUf3 C XAMAGL X CGAA AGAGAA 1784 ~AMwC= C CCAArr 682 H-CF1C 89 GUUCCACG CtflALA X 03AA AGCU=J 1785 CCAWr T CIGAA 683 H-SRF1 90 AGrCCACc rA~iAGL x aMA AAGCUEXX 1786. CCA=I C GGUAACr 692 RMF1 91 CA303 CUGlAIG~L X 0AA AGUKXC 1787 GIUAACr C 'TtCIG 694 HSFR 92 GCA=X33 CarAin X OSAA ?LGLAtt 1788 GAACI C CCtt'I= 704 HSRF1 93 CUCCALX CUflAIfAG X 0CAA AXGLXX 1789 Ct'CI= C CTIGIG 749 HSRF1 94 CMACAWZG CUGADCA X COA PAflXW 1790 CAG=~ C CACIGIM 780 HSUCMF 95 UtCA= CU=~ X C14 AGUOJ 1791 CPIC r A =CCA. 784 HEF1 96 GCGJEX CMU3G X G:7A ADGIMfl 1792 CACMr A TOCAA= 802 H..EF1 97 UtLflUALIA COCA=XW X CGA AOC 1793 TI0I' C T~rAA 804 HSMM 98 ttvuVJC2 C~ X~ K GAA AGG 1794 030C= A TMCA 806 RSM. 99 CAmUjUG CUCALU X CtG.A ALGP 1795 GCI:RT C APAAI 835 H-{MCF1 100 GOCAU CUXAUMG X QGAA A033 1796 AGOC= C A==C 838 HSRY1 101 UX) CML2 X COA AUA 1797 COtIC1L C COCA 859 HSERfF1 102 tUACU3AC CtMAIML X CGA ALM 1798 MCM4 T MGENA 862 HEF1 103 CGLUt1W CtIGAA X O:A ACALA 1799 CIGATI= C ?P1rAAC 866 HSF1 104 UGCCC= CMUCIAG X OM ACUCfl-A 1800 ITICL A AALXG= 878 RSfF1 105 GCACUML CUGAUGA X OGAA ACEt)t 1801 a~n A cIrOI= 881 H.S'F1 106 GGLCu CUUUM X CCAA AGUAC=f 1802 CAM=r C AGG 941 HSEIP1 10 GMUA= IGAM X K A ACCCC 1803 G93= C CGI=I 964 HSEF1 108 LXt-ZkUA CUGAWlPG X CrA AMCO 1804 rOOr C MTAA 966 N.SfMl 109 GCUtfL~a CUGUGA x a3A.GG 1805 C30Cr A CatUMA 969 HEFM 110 GUA~aM CUGAUGAX K AA AGkM 1806 Ct'I~C A CAAGC 976 HSERYFI Mt ACCU=f CXUAUGAG X 03A AGU=X 18077 TAA r A ~CACACr 1016 HSM 112 AGLtULXA CU1XAL X OMA ACCLttU 1808 TGP A TMAGCr 1018 HSE1F1 113 03AGU CUSAUGA X CCA AMC 1809 GA70= T CACI= 1019 H.SL1 1-14 LtXM u CLIWIA X CA AAA= 1810 AM=.T C AGAI= 1025 ,HSERYF1 115 GCxxr CUAUA X CA AGUtIPA 1811 TIC= C GAA= 1041 HERF 1.16 CUrii= CUXUXPG X CGA AUOCCU 1812 CAGrA C 7GOAAA 1068 HSERD1 117 (XCALG f CUADM X CMA - GO 1813 AC33 C CAIt'I 1073 HSM1 1.18 Gmx anvLXG x amA Aa b 1814 Guia~ c m32= 1113 RMfF 119 MCA CLX X~ K3A AO C 1815 'TOM= T TTI' 1114 HSERYF1 120 AC=J CLtgVIXAG K CA AAC 1816 091I= T AIM=~ 1115; MUM'f M2 CAC~ CUXAUGG X CMA AAGOCC 1817 GGOTI A 7OIG7 1139 HSE'F1 122 AE~tr= CUMXWX~ K A ACOOCU 1818 GCG A G3AAT 1148 MUMf 123 CUCa CtLIXAL K OMA A1XTJC 1819 GCOAT T G0C2 1163 HSE1F1 124 CAOW CMAMflG K CGA AGCP 1820 AGI=z T CAtIG 1164 HSERF1 125' t~kG CUGAUGAG K CCA AGO= 1821 cGMGr C AG3Ci7 1190 HSfEY. 126 AG33 CxLUIGAI X CA AC73 1822 C=CGO A, CITOCCT 1199 HSE1F1 127 tUGGUAG& CEYM fl K CMA At3A 1823 LTGCT C 'CTAA 1201 HS~EM 128 cVtmm cuiA K 0:2A AGAIO 1824 GCCik= C TAMD3 1203 HSF1 329 G~xm anurIflG K cGA AGWGIM 1825 cctAtT A CM= 1230 HRER1 130 a;03 C=WW. X CA AM= 1826 0=0=~ C AM=It WOO00/61729 PCT/USOO/09721 59 Table M1. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1240 HSF1 131 AGGUG=t CCAMM X CMA ACt 1827 GGCX T AGCLCAr 1241 !-SRF1 132 CAGGGG OLMAfl X 03AA AAC1D= 1828 GGCIrI A OM 1249 HSRYF1 133 AAGIJ CarA=, X C7A AGU 1829 AGCt' c Arrr 1256 HSE'F1 134 UCCAG32 CUPMAG X OGA A tLI 1830 WTAUr T ITCCC7W 1257 RS~F1 135 GCC= CUCAAGfl X a:A AA3 1831. CA'i rT T CCI 1258 HSEEIT' 136 Gar= =CAucp x a3A AADGIJ 1832 ATI'IT C CrIGGCC 1270 HSF1 137 GCtCA GX2AZAG X 03A 2AL3tC 1833 GA~Cc A CIrfl3I 1278 H.EMM 138 (XGUJ CLWIx X 03AA AGCC 1834 ACIGT C ?CCA= 1290 HERF1 139 U333SAA CMXAIX2AL X 03A AGCfl 1835 CAO= C arIttt= 1293 HSEd~1 140 CtIGXX CU3AJ23zL X CMA ALGiA r 1836 GC =~t T CCCCAA 1294 HSERM 141 CCUnn= CAXMtX2 X CSA AACP 1837 G3Crr C CCAC70 1328 HERYF1 142 CCCA.CA aflAMA X CMA AGLfltX= 1838 CCAG=C A aTGI=i 1340 HSEF1 143 OCLMA= CYAtXZ X QGAA AGC; 1839 TOM=2~ C Io= 1345 NSRM 144 CtAUGA CtrGIX3G X 03A P3AGC 1840 crtc=' c Am=~a 1350 FSiF1 145 Gr=t)=. Cm~wG X CGAA AOMUGGC 1841 (ri'aC: C ATA 1373 RS4z'F1 146 C XtTXT COGAUGX~ K A MOM=~ 1842 CAG C CAA0; 1391 HSRF1 147 AGAGA CXUIX2ML X COAA ACACAC 184 c=Iiur C Criciw 1394 HER1 148 AAGM CUCMAIG X CMA ALAC 1844 cGm T cIir' 1395 HSU'F1 149 CAGG CAnLIGA X CMA AGACC 1845 GIII C TCIt=tII 1397 HM Y1. 150 UCAGA C!pamL X CPA AGAAGGC 1846 arwiwr C ccriamI 1400 HSELFF 151 GCUACA CMflAfL~ X MA AGAGA 1847 CIrItWI C 7TAWC 1402 IH E1. 152 Ctxxn CUGAUSA X C13A AGGGG 1848 TCIWCI' T GrGCA 1405 HSR 153 AIJCI-= CUGAUGA X CGA ACAG0 1849 OCICri A GOAG 1414 HSE1 154 tmrCCA ax~IX;L K CXA ALXfL= 1850 GC~AGAA T CIGCAA 1415 RSMF1 155 G3tfl= amuoIG K aIA AALTJDCUf 1851 CONMATr C TGACA 1430 HSERY 156 GGCCG CGAD3A X CA ACLX= 1852 ALCA~ C TCIt= 1432 HSEMM 157 C GAUGA K CGA AGC 1853 CCAIGTr C IGCtC 1456 HERF1 158 GAAG= CUAA X CA AGCA 1854 otCV~rGC T GAAit 1463 HSRM 159 AAGUUrn CUGAUGA K CO&A AGUUA 1855 TIGALCI T CAA 1464 HERM 160 AAAG=J CLXIGAGA X OA AAGGXUi. 1856 IGAAI C AAIT= 1471 HSERfF1 161 UrJMMrI JGXM XtIL K = ~AGCU k 1857 ICAAG T TIGIAAA 1472 HM1F 162 AUrJXXIA CUGAUGAG X CO AGC= 1858 CAAGT T 'IAAAT 1473 HSERY1 163 UAULXXMtC CLxGAUMG X 0A AAAG2CXU 1859 AA13T T GnUAAAk 1476 HSEEM1 164 MJr~U= aXMtxNG X 0A ACAAAGC 1860 GrrI= A AAATAAAA 1481 HSMMF 165 G3mG= U AUG Q IX~ K AA AILXXtjDA 1861 'IUMAAAT A AAC= 18 RMTIA2A 166 U3333 CUCAzg X 03A AGUO= 1862 G303= CTAO 20 HU2iM2A 167 C.... UAUt= X CMA ACARL30 1863 CICAl A LCtCCA 30 HtIAM2A 168 akm ajaXJ= x oA 1A Xtm 1864 CtCX= C CMCtI 33 tJWflA i2 169 UMLMk~ CUAIGA X CA AGGX 1865 CAGCr A Ct~IGM 40 HUt"AM2A 170 OC0 U C~LGLIP X OA ACG3I 1866 TACO= A AGC 55 HL14M2A 171 CA3r CUA= X CA AGOU03 1867 GCA C C3G= 68 HMPM~A 172 Gt'C=L CUVIA X C3A ACGA 1868 CGIG C CIG 79 HJ1IP2A 173 CCA CLIUIX K CCA AC3 1869 G33 r C GO:C= 85 RHfMThA 174 a~LtW anflCAG K c:A AGMCMC _1870 GIrttT C GItt'C WO 00/6 1729 PCTUSOO/09721 60 Table I. Hammerhead ribozymnes targeting UATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 91 hujI-rAT2A 175 LIM CM-AM.A3 X C A ACtCCCA 1871 CIt I' C C-Ca 103 HUMA2A 176 cG3ALMAA CXfLUMA X C1:A AxU)Cr- 1872 CCUACT C CA=Ci -106 HUMAT2A 177 tLr.2-.P CtxA~rIX x coA ?A Jtr 1873 GACIC= T CrCII= 107 KMAT2A 178 CtXA?0J CUGXUGA X CIA AGCJJU 1874 AACICCI C Z~CC7CAG ill 1itJTA2A 179 GCMOMn CfLrALr.N. X CIA AGUMAM 1875 CC'lCAC TcAGGG 213 HUCAT2A 180 C330=r CGJG~rL? X CCA PGAGflAA 1876 TICI C WAG 125 IRUMTA2A 181 XXL CtXAX2P X OMA AM= 1877 GxC= c CMCtw 129 HJW-AT2A 182 cGOM= CtflAIMX~ OMGA A033C 1878 CGTQIC C CCCI=t 134 RMTA2A 183 CCJlG=3 C1AOG KM A0~33GG 1879 CCtItCc C CCG 156 HLMAM2A 184 GCAA03 COAnA X C3A A033 1880 G70c3= T GCUrI= 161 MrATA2A 185 U30 CUr-Atr-A X CGA A0CAC 1881 CGTIG=t C T 264 Hur42A 186 OaX)= CtUUMA X CSAA AGW 1882 ,CCCtGAr C XACCC 291 Ht3CAT2A 187 GJtAtTl CarAL[ X OZPA AGUJt 1883 CACAACr A CA7GC 317 HtUTh2A 188 C~U3 CflAtJM X MAA AD2ZA 1884 TI=~t C aNOM 334 HUMT2A 189 XPB1AA CMGA. x aMA ACLXA 1885 G03=~ C TItTIUA 336 MCAI2A 190 GIAtMAG CUGAUGA X 03A AGC 1886 0C=I T CrCAAIC 337 HUI;UA 191 Lr-UtflAA CUtX2G X C3A AAA 1887 GCGi=r C TIAA 339 MUMMT~A 192 G.flAJU CUtflJIA X COAA AGAAGA 1888 CGi I'mr T CAATC= 340 HLMATA2A 193 ACIU CUGALM3 X CMA AAGAC 1889 GIr~IrI C AATC=~ 344 HUM.'2A 194 GUCGAtJ CUGAMAGL X CGA AU~fA~ 1890 WCI=A C .ALI03c 349 HMVA.A2A 195 tLXrxz CMUA X CA AGO JtJ 1891 AAIt r C GACI3C 354 HUAT2A 196 tUtfl2 CLIGAUN X C3A AGICA 1892 CctIGAcr C GaG3C 369 MCTAfl2A 197 U03CLIA CGUGG X OCA A033GUL 1893 ~CAAC A CIUC 372 HtJZU,2 198 CflUt= CGAUGA X OCA AGPD 1894 ~COCCr A 'XCAC 386 Ht3M.MA 199 ~G U CLXIAXPG X OMA AG33r 1895 ACCC ' C -Xfl030 397 HUMT2A 200 CUMW CUPMA X OMA ACC 1896 CGO r1 C =rACAG~ 399 HadT2A 201 GOU CUI., X CM AGC 1897 C30 C CMC 402 HLZMT2A 202 C303 CALhtG X 0:A AGAGa 1898 03M=w A AC 453 HtIA2A 203 UTnOAA CUGAM1X K MA AG13= 1899 ot'C~Cr T G1'1CAC 456 IMtAT2A 204 G~aXLUC CUMMA X~ K MA 2ACAGU 1900 ALTIC= T GCU 470 HULM2A 205 CCAOk UAX2G X CCA ACC3 1901 GCOrG T 'IM1I 471 KZtAT2A 206 GOA CUAx~LA X 03A AAC33 1902 CCC3r T GCCI3 502 1HJMM.2A '207 GccrcAG axALxAG K CMA AGOOD 1903 GCG C 'TCIGO 504 HULZTPM2A 208 :-711 CUMLXG K OMA ACGO 1904 AGCC C 'I0tC 540 HUMA2A 209 LtLUMAG~ UA~LIPG K CCA A033= 1905 GAGOr T CICOAGA 541 ME~~AT 210 MMUr1M CUAUGt X CA AG3C 1906 POCCi' C IOAAAC 543 HLZEATA2A 211 GCGUwU CUGAW7A X CA AGAG3 1907 CtwCwr C CA& 564 HtI3AZ~2A 212 CALX= CIXP X OA AGO~a= 1908 GC C .3CI 591 HUMSTA2A 213 UAACG CLuMMA K COAA AGUO 1909 AGC~CT C TCITIG= 593 HUMMMAA 214 auku anuxN G X OA AG-' 1910 GCr-AT C 'IGM1ft= 599 HtJAT2A 215 (flXa= CGULg X OaA ACCM 1.911 CTCIMUI A Cax 639 KXtM2A 216 AGCCC CCAI X MIA A==l 191~2 C3:2 C M L C 648 KUMAMA 217 anzo,- muuxw x aA A==C 1913 AmU i, c ccrm=C 652 MZMM2A 218_ aGO aUiML K OA Aa.A 1914 Gt'IC= C ?LttCCC WO 00/61729 PCTUSOO/09721 61 Table III. Hammerhead ribozymes targeting, GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 659 H1-M~2A 219 GOCLIX CLGUA X OSA A33GIM~ 1915 WCACr A CAM=C~ 672 HUM'A2A 220 GOGGCA CX3AMfl X COA ?W33CXGt 1916 ACCACr C ~TO= 678 142-A 221 AA~AG CLPL X 03MAGCAM 1917 ciTCTG C CCC=I 685 HUMTA2A 222 AAOCCAA CtflAMAG X CGAA A~)3G 1918 IC~CCAr T T1'I3I 686 HZMTA2A 223 GCCA CD3AMAlG X 03AA -AGG 1919 Ct~LtTP T 'ICI'1 687 HLZIPMA2A 224 OGA CLIUrAGX X CCA AAfl= 1920 CCC= T COO'=C 688 ELDIMMA 225 G3AA= CUGADICP X CUA AAAA=f 1921 ~C'ITI C GOrt' 693 H9ZMIk2A 226 GL3LMn CtXAUGAG X CaA AGCG 1922 Tr'IC= T CtLCCAC 694 HUMMM2A 227 CGfLGD CUGAUGAX~ CSA AAOCAA 1923 TICIT C OCCCA 720 ELZIMMVA 228 GGXG CrAXr.Z X CXPA MfLtr 1924 GGIAr C TCWIA 722 HUMM2A 229 AG~aXA C1M3AIMG X CXA AGACAG 1925 A~Aiuicr C CIGCAP 731 HU!TLT2A 230 CUtIGG CUAUWG X 03PA AG3UA 1926 Ma=tt A CX*C= 750 HULMM2A 231 APGE= aflA1 X CXMA A0CO0 1927 GON C ITCC r 752 ELZM2A 232 tf~LrflAIX CMALUA X CCA IAtACtf 1928 -~CrGO C (~CAGC 759 HEJIVAMA 233 COGAGAIJ LMAXGA X C:A AGtflM 1929 'ItM=I C AW'I'I 762 HZIM~2A 234 CtAA CrAfLUPG X CIPA AMA=~~ 1930 AtIL= C TIt= 764 HLMAaM2A 235 AL7C;G X K 7A AGAUGAM 1931 CtI~cr T 765 NJM2A 236 CMALGA X CXA AGAGA 1932 crcAWI c conmb= 776. HUM.MIA 237 GtfLAAc aX)IX3AL X GaAA ACCtt 1933 C33 A GIC=t 779 HIJTPLT2A 238 UCnnxt CUALM x a:A AaM 1934 G33 T CA~aP 780 924M.2A 239 CI03 CUAUMXG X MA ACL= 1935 GOGT C AOL0; 808 1uMM2A 240 U33ACMt MaM X OMA ACfl 1936 GA0I C AA12C 813 RMUM2A 241 ACt'tf C X2.AUGA X 03A AC JtGA 1937 MI) A CCAGr 822 HEUU~2a 242 COMMi CUAUGL X CINA AO .... 1938 C~G C ACGA 857 1fLZTA2A 243 GCC C C tX~ K AA A030A 1939 G03= C CCI= 874 HIZEAZVA 244 AUGU~ ax2Lx;G X OA ALG30= 1940 CCAGr A GC=. 878 HUMUMA 245 GCCAA CLIGGUGA x C1MA AMG 1941 GCnY~ A CIALL= 881 HUiM2A 246 Gouo= CafloI X CGA AGAC~ 1.942 TAGC= A TG3CAC 899 KHM3%M2A 247 GUOOUGM CIGAGA X CCPA ACA3 1943 AMC= A @DACACA 913 FKMU:2A 248 TWLG" CUtADA X CCA ALI33 1944 CAC C CCAC 921 REXM.TPI 249 DA~m= ctxAIXG x C:A A~XX 1945 CCC A CIK 'r 927 HL24M2A 250 GCCAA axwi=~ X CMA AG0GA 1946 cnkor C cnk1T= 930 HZGA~2A 251 ~CAM CIAxwiG X CA AGA 1947 CWrCI' A IGIG 954 MU=A 252 cotmn axw=~L X 03A AaL=f 1948 ~CCAC A CACA0 967 HLI4M~2A 253 mmoc axAL7wL x 0:A AGt J 1949 AG3GCr C TIt2= 969 HMMM~A 254 03=axw= X 03A AGCL= 1950 ~CIC1' T aAC 970 HMIMA 255 OCtXPuG Kx~A X OA AAAGC 1951 GItCr C AC 984 HMkJ~2A 256 CCCtCA CCAUGA X OA A~~t 1952 C33M= T CCI'2= 985 MC2A 257 ctcccA cttm G x 0:;A AGC= 1953 GOCP= C C03 1002 KHUMM2A 258 MAA=Ef CanAtXMG x aA AP3C3G 1954 AC0 r C CAGC= 1008 MUU2A 259 Lmo arjo= x OmA A~XM 1955 CICtkzr T CALtCC 1009 EU.a2 260 uuAG= axxmG K CGA AAan 1956 'TCCIT C ACCCCt'A 1016 HtJMM2A 261 GO== aMX; X CA PM)M 1957 MA==c A AGM 1034 KZ 2a= 262 Aam axw K o3AA Aan 1958 GAACr C G'CI= WO 00/61729 PCT/USOO/09721 62 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1037 HtILATh2A 263 MfA=J CtKAI) X CMA AZAGWU 1959 .LCtT T WIG=I 1038 I-U1=2A 264 CMfAAA Mr1ALM3G X CSA AA3A= 1960 GACIT C CGi= 1043 HtIMTA2A 265 GCCUUCfLr CUPMAG X OMA AAGAC 1961 GI'TCWI T C~AGAG 1044 RHUTA2A 266 GOCUtnj CAMAxn X CMA AAAGA 1962 IIWC' C AGAG 1063 1-1~trAk2A 267 CCACGJU cu~mr.c x CXAA ACACALU 1963 GAGIGIMr C APC IGI3 1088 HJIMTA2A 268 CCOCCAGA CMAMAG X CGAA AG3Jtf 1964 CACc'c C wTCT 1090 HtJPLM'2A 269 CCA CtflAUGA X O:A AGG 1965 ACC r C TGIC 1116 HtZIMM2A 270 UxCACG CrUJiW X QMA ALXUt= 1966 Cfl3CC A (CIUI= 1137 HJ-,A2A 271 LIGL3UA CEYMMAl X CMA AGCOA 1967 cIGC r T CML= 1138 Ht2IMM2A 272 UtUUA CrAGA X CGMA AAC 1968 'I0rr C TACMIA 1140 HMT2A 273 t)rUtJIJ3 CXL)MG X CGAA ?AAA= 1969 CriCr A CACAG 1.171 HUWAMUA 274 GCUUGAU CfLGALMG X CXMA 2AJDUXf 1970 LCGACCr C ATAX 1174 HUCAT2A 275 Utn0uu CMlAMAl X C:A ALM=tf 1971 CICT C AAGCrC@A 1194 HurMrT.2A 276 UO33C C~riAXP X 03A ACA 1972 APAIUI C OOlCt= 1220 .HMT'MT2A 277 -AUULC Cl-,UA X 0:2A ACG 1973 GCACi= T G1XAAAT 1229 M17M2A 278 CGUtnAC CAMAtr X CMA AU1XUC 1974 GIMMAT T GTAGC 1232 HIUfrMM 279 UGUOfl CLAMG X CGA AC.AUU 1975 @AATI= C AGACA 1251 hUIUkM2A 280 GGOO= CUAnUiA X COA AGGU= 1976 MC= T AnTGXd 1252 HUCA2A 281 aXAon= Xtm x aA AAGfl3J 1977 AC~CCI' A 7MO= 1282 HUI.M2A 282 GCGt= CtLCU X 03A ADLAG= 1978 GACCIG C IGCAAiO 1300 HUZ.TA2A 283 ULXXPZ CUGAMA X CGA A0LA: 1979 'IGI t C MMA 1302 ELZrI.Th2A 284 GCUM CLItXLM3 X CMA AGG= 1980 'IGIC= A CACAG 1305 RE14MMM 285 GCAG= CXLU= X CCA AGA0 1981 cC ~Er A cAG 1-321 HLRMT2A 286 GOCCUGU U X X~ OMQA ACAU=f 1982 CACAA T MCA 1322 M1UkT2A 287 tGOUX CUAUX~ K MA AACAUL)O 1983 ~AAA= A ACG 1354 HUZ.Th2A 288 CGG= CUGAUGAG X COA AIUttL 1984 GAG C CQJCI= 1361 HUZIM2A 289 CtGG= CUAMinG X COA 1ALr)nPJ 1985 'TCCGAr C GMA 13*77 HUATA2A 290 ALCUU=f CGAMA x aAA RAU=X 1986 GAAGi= C CACA~ 1386 HL14MM2A 291 tL2tUrVW CUM= X C31A AC XfXM 1987 ~CACAA~ C CAGA~ 1416 HUIM2A 292 GCXtLC CUGLU.PG X CGA AGACO 1988 GOG T OMGA 1417 HMfrMAA 293 PAttt= CUAMX~ K A ACX= 1989 GAG1I'r C GACA 1428 Ht1M2A 294 A=u CGUtX2G X COA A.AGtt 1990 GG(3 C AAGIC 1449 HUMM2A 295 AG03A CUCN X CMA AM=~~t 1991 GGAGAAr C ACXI 1452 HUCAM12A 296 TPGM CUAMAG K OA AIMCEMX 1992 GAG C CI'1= 1458 HM4M~a= 297 antX an C1ALXIA K CC4 AG U 1993 ATC r T CALICA 1459 9-14MMA2A 298 CXIWO CXIXGA3 K CGA AAO~ 1994 ITtC1T= C AGUCG 1493 R14MM2A 299 GU3 C JM1XG x aA AGU 1995 'i00CAr A 7030 1504 HUM2M2A 300 AAO COGAMW K CGA AGU 1996 GOCAT~ C C03Cr 1512 HU!MM2A 301 AGnXW CU .2 X~ MM ~AG3 1997 OtC03= T CAGC= 1513 HUIMTA2A 302 GAGU CtMAMfl K 03A AAO 1998 CCIT= C ACI= 15921 HMMMA2A 303 tflfl CUGAUGPG K aA AGTfl 1999 CAGC1~ C C3ACC 1531 R2M=2A 304 GL03 CtflMIW x aA AUOUJ=f 2000 GGCAA C CIGC 1541 HtIA2A 305 Go = amAim K GA~A Ago 2001 Ta=Er C ' AC 1552 HUMMflA 306 G~o Ctu npr K C:A ALM=~ 2002 A=CT~ C U=tt'I WO 00/61729 PCT/USOO/09721 63 Table IH. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1560 HUr.NT2A 307 GOCUOGA C~r.AtLr-G X C GA AGG33 2-003 ~CCA r C CCAC 1563 HUMTjA'2A 308 AGG CtnAMnG X 03A AGGAD= 2004 CC==w C aCICT 1570 EJU'M.A 309 CCGAAGGA mrflAmAG x a:A A03CU3tA 2005 iTCCAxtr c mr 1-572 HUJ!MATA2A 310 GCCXAAL CA=~Il~ X ctA AGG 2006. CAGC= C cI'ic= 1575 , KMAT2A 311 aGtUnxt CUGAUEXG X COA AGSAGLJ 2007 CCIr- T G33C= 1576 HUDCAM2A 312 GOmU= CU3AMPG X 03AA AAGS2GG 2008 C~TICT C G3OCCC 1593 HMMT2A 313 CCAL.)x CUCAMnG X 03AA A33= 2009 CCACC= C CPCA 1617 HUMAT2A 314 CtflJUCtC CXULYUAG X COA ACCttAUG 2010 CATG=r A GXAACAG 1634 HMEAT2A 315 Ctttr CtXAUflA X CGA ACGUJ 20U2 ACGGA=T C GCA f 1649 HUMTA2A 316 CAUCm CUAxUix X 03AA AGO 2012 G=~f C C0IG 167-3 HZU2A 317 G30m~J CUGAI) X CGAA AGGJUELI 2013 C~AAt= T ACCA= 1674 NU~rA~2A 318 tU0303 CUGMtWAG X 03A AAXXJ 2014 AAACCI A CtCtG . 1687 HIAM2A 319 GLXu) CUAM-Arx X OMA AUL1C= 2015 CtCA= T 'iCtCG 1688 HUZCAM2A 320 ciGM= UAWAG X CCA AMU=X~f 2016 CCA'I T CCCA 1689 HUDTPX2A 321 GOU30~ CtX3AMAG X CGA AAA=t 2017 CGM=iI C cam 1708 HU~rAMr2A 322 a~xxm anymG x aA AMIGXJ 2018 AC=mc c C = 1724 HUWAM2A 323 oan=r amww~ x a:A A= 2019 CCO=r C arCA3 1740 HUCA~Th2A 324 arakmA CtXaUrAG X CGA AGOO= 2020 ~ccr c iwi= 1742 HUCAT2A 325 CCt CA CflAMAG X COA AGAG3 2021 CtCCI' C CIGCP 1775 HUM2A 326 uEjm= ctrwu x C@A Acmam~ 2022 CCG T ACT~IGA 1776 HZEAT2A 327 AIUUCCA CGAUGA X CA AACEXUW 2023 CAGCA'r A CIGTI@A 1787 HEJ1ATA2A 328 C=X~ - IC1AlA XA ACILXtCC 2024 G7AA~ T CUCA0 1788 HIMAT2A 329 axOGUGM KU M X CC;A AACAUXA 2025 'IG.A=U' C CtCA 1810 HMMAZI2A 330 CAM CUAnUtx X CMA A3AC 2026 GC~I= C COCA 1838 HU4~2A 331 AUC~ CUA'P K CGA ACCCC 2027 cWi T IWIC.T 1839 ME.~AT 332 CAIOCAG CUADI X CGA AACC 2028 GI3 T CCI= 1840 Fff %T2A 333 CALA CGAMP" X CA AACLM 2029 7033IT C CGt= 1854 HUV~A 334 CUCAAAC Car--AG X CA AU 2030 TOGACAM T GrIU 1857 KZMT2A 335 GxUxC CIAUGAG X CA ACACGE 2031 riPD= T TOGAC 1858 KITPLTA2A 336 UOlUfl CtIGAIA K CGA AACAACUG 2032 CArUI T G3jAC 1879 BLIM2A 337 UCLMiA C,-49XM X CA ACUflUC 2033 GCLX T 'TIT1M 1880 HUDZa22A 338 CCAnMn CLGKA X CMA ACfl= 2034 GAC1'r T ATnkA 1881 HUTPX2A 339 UttrnP~ CVIGAM X 03A AAAGUG 2035 -ACAA r A TMGA; 1885 HU.M2A 340 CUtXXrn= CIAU2G~ X COA ~IACAPA 2036 CrrM=~ A GAGAAAG 1923 FHJL24UA 341 CUUnUmA CUMUA X CGA A V 0 3 2037 GCACA T I~%GA 1924 IRMCAMA 342 acucatVA C MtXGL3 x aMA AMOLJ 2038 ~CACTr T 'I'1GAM 1925 HLMrA2A 343 UOCUULA CLIGAMPG x a3A AAAU= 2039 Ad'IT T TAAA~ 1926 HUCA2A2A 344 UUCCxUM CUGinA K CA AAAAOOU 2040 ALCTrr T AGAGA 1927 MUM A 345 Urxmxr CLGUGAX K 7A AAAAAfl 2041 I'Tr A WOMM 1942 MLT2A 346 UUUtD UWC; X K A AMC=tJ 2042 AAAGGT T A3AAAA 1943 HUW-AT2A 347 UUUt'Lt C UGAMAG C A AAUCttXJU 2043 AAG A G3AAAA 1953 HLZM2A 348 AAALMAAIJ CUMLU X 03A AUUUUUOC 2044 GCAAAAAT A ATITATI 1.956 HJi~AT 349 GAAAALIA CUAxwM X COA. AUXLJU 2045 AAAZAT T MkTII 19 57 u.M4M A 350 1 AaAu anqrIXG- K A Amxu,=J 2046 AAM) T AT-I--- WO 00/61729 PCT/USOO/09721 64 Table MI. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1958 MUAT2A 351 CAAAA CMAiLr-G X CXIA AUtLIJ 2047 PATAATrr A 'TrI= 1960 1UMAM2A 352 kAAOCAA CMXAIGC X OSA ~IAOXU 2048 TAATF=. T TIGCI'r 1961 HUUA~2A 353 CAAGGA CXAWLXG X CXtPA AAALAU 2049 AITaT= T TG~C'T= 1962 HUT2A'2A 354 ACAAC~ C)3AWGK X CMA AAALJAAU 2050 AI'TIT= T CItI!I 1966 HtIATA2A 355 JMAAACAA CUMUCI X CCPA AGCAAAAU 2051 ATITIr c TIUTI= 1968 HJIMMA 356 UUAGAAC CWrAIflAG X CG.A AC4AA 2052 TI'IGI= T UTMA 1971 FUCATA2A 357 ULURPEA CXMAU3P X CCA ACAAtGLG2 2053 GCtIC= T TCAAA 1972 HUM3AT2A 358 aLIuXuMG axiMAG< X CXMA AACAAGAG 2054 CI~~rrI T CIAACAAG3 1973 HLR4MT2A 359 CCUt~aM CUAMAGN X CtMA AAACAAPA 2055 TIIIri C TAACAAfl 1975 MUMlIMA 360 AGt=tXJ arXALXAG X GO.A ACAACA 2056 TM~T=t A MALflT 1984 HJMMA 361 AAGUtn CLIGAMxG X 0AA IAOt'ttf 2057 ACAA= T GGAAr 1992 UM2A 362 Am arJGDmw X O:P AaM=~ 2058 TICaAWr T GMD.1C 1.999 RiUA2A 363 XMG CLrA X OmA AC = 2059 T=CgIr C T5DT 2006 HmMT~A 364 ACUUOMA CUAUGx X CGA AOCUAG; 2060 M IGI= A Iur 2008 EU=2 365 mw=~fl CMtA X CM At2AG= 2061 TGG C CCAA=C 2015 HtJATA2A 366 AC~CWA CE)3AMAG X CaA ACLJt= 2062 'iCCCr c 'iiCO 2017 HLZMA2A 367 AA GC CIAUGAG X CXAA AGAt= 2063 CCAAKic c cauitI 2022 HLirAT2A 368 0AGAA CM ~I X CGA AOXMM 2064 wiCTC rO T CI7CW1 2023 HUMTA2A 369 CCGA13A CUAIJGG X CrA AAC3C; 2065 CICCiT C TICI=f 2025 HDCA A 370 tUCOG3 CUCAUCP X CCA A~AJ 2066 CCGCcr T CCC30 2026 , EJ.AM2A 371 AMCtttG CUMUN X 03A AAA~X 2067 C3==r C CIC.3T 2029 Ht3IP=2 372 CAAtX= CUGAL1 X CMA AGAAA 2068 TItTrt'I C G3I'i= 2035 HaUwT2A 373 GAO CL12IA X OMA AM =~ 2069 CIOT T GOC 2043 HUMT2A 374 GOAAfl CPLUA X 03A ACO 2070' 700= C C'I= 2048 Ht3rA2A 375 GCCC=n aiUIxMG X OMA AG1CC= 2071 cG9t0= T GCGO 2058 . KJZMTA2A 376 tUnOCt= C YIXALG X CGA AGCCCfl 2072 OCG C TG33 2070 HIUMATA 377 UCCAC CEMX;XG X 0:A ALCEt 2073 G0CGT T 'TGIIU3 2071 Mrg~a= 378 GUCCA CUAMtA X CMA AA=t 2074 GOM= T G033C 2082 HUCAZ2A 379 UOC03U CLxIGAUGW X CCM AG 2075 GOOGAT C A ICC 2095 92CAT2A 380 GAGAA C!XPtflG X COA AGOM13M 2076 'IGLAr C TICI=I 2097 BUMM2A 381 akLM aiXWJM X C= A)G=~f 2077 C iCr= T CC=tI 2098 HUCA2A 382 caa~ axMXXM X C:;A AP(GAG 2078 A~Crr= C 'iMCM= 2100 ELDVAT2A 383 AGpkA CIGxUMG X COA AGAAG= 209 07M=ic C CItI=i 2103 MUMM2A 384 ai3A= CxLM X 03A AGAA 2080 Ci'tICc' C 703c= 2109 MUM.~2A 385 MAO=~ CLIUM X CMA AG~M 2081 CICI=i T C'CCI T 2110 HnM2MA 386 CAkGG LxIxUGA X CMA AALX 2082 'iCIIT C CW~t'I 2114 , RXAT2A 387 AUICG CtX;Ui X CMA AGGA 2083 Grtt C 'IQAAT 2116 HLITAT2A 388 CALnUrM CtX;UX X CMA AGG3A 2084 TIiCO ' C 'iGA 2123 HMM2A 389 AMt C GUM X CGA AIUE.~ 2085 'IC'IGAAM A G00ALr 2132 FKMAT2A 390 CCAtU3 CLGUGAG X COA AGXX 2086 GLXPT C 0 2193 HtOflAMA 391 cOLr= CEXG.L X C:A AGA 2087 'IGIC'I T 'IML= 2194 HIM.M2A 392 U330 LtIJGAGA X 03A AG= 2088 ocI~IT T GAO 222.5 HCAM2A 393 Occa J Cta~iMG X C:A AUUM ! 2089 GA= C AC3 2235 gzUmT2A 394 -Tuam G amxmIG x C:A JALa t 2090 C03 C CI=M WOO00/61729 PCTUSOO/09721 65 Table M. Hammerhead ribozymes targeting GATA transcription factors (1, 2. 3, 4, and 6) and the complementary sequences 2246 HLMIMI2A 395 OSG CMXAG~ X CrAA AUEXCCU3 2091 OCDGA T OC*~G 2247 HL113A2A 396 CCA CMfAGA X CCA AALXl 2092 CAMA= C CN 2253 HUMA2A 397 AmGhL= CMUMXG X c:P.A AGL~A 2093 TICGAO~ C 03n 2257 HUGAT2A 398 UU)G33GO OflCD3G X CMA ACC-A 2094 AGItGOT A CtCIM 2271 HLICAM2A 399 GOC CUGAUCA X CZA AIUtnJW 2095 CACAA T C= 2272 HtJITA2A 400 L'33t= CU3MAMG X CXMA AMCLUJE 2096 AACGATr C CCAXCA 2290 HLIVMh2A 401 CUtrtfl CUAUG3 X 03A A~CCCGC 2097 GOir C ACzGCAAG 2309 RubM A2A 402 UOCAAGA CAXMJJG X OaA AUGnmxW 2098 AACAACAT T 77CrrGPA 2310 tHfrA2A 403 UUtCAG CU3AIr.G X QGAA AALTGtfl 2099 ACAA'IT T TWIGAA 2311 92CMVAA 404 CtUtMAAG CtflAIM X CGA AAAU=lJ 2100 CAACA=II T CI'IGAA 2312 HWTM2A 405 CCUUUCAA CUDG X OM PAAAIAXJU 2101 AA.TI= C TICAAA 2314 HutIrATA2A 406 CtCL=t CMAGA X CMA P&CAAAX 2102 CATrI'= T GAAG3 2329 HtJCAT2A 407 GAUC=~ Car4UJC X 02A ACGULtC 2103 QOAAAQT T TRCT 2330 HICAT2A 408 GGAU= CtMIXG X OMA AACGUUU 2104 GAAIT T CAGA 2331 HMVJIM%2A 409 AM;=n CUL-A 3 X 03A AAJtJEJ 2105 AAA=T C C~rAIW 2337 HUMSAA2A 410 AGWlACAL3 CUGLfl-A X 0:1A AMMMXA 2106 T~TCCAT C CIGICW 2342 HUMTA2A 411 G(XCAAr CMXAGAG X COA AAG= 2107 G=tI~r C CIrr= 2346 HMTPM2A 412 CAIOCA CLIG X OMA AG0AA 2108 C7G3CCC T 'I=ri 2347 HUMAT2A 413 tMAAAGCC fLrAt73.A X CMA AA~a~ 2109 ITGM=I T GoriTIh 2352 HL143AT2A 414 C03tE1C CflAIPG X MIA AGC PAA 2110 ClrrI= T MAO= 2353 HERC40WA 415 UC3!X CM40lAG X CMA A~AA 211 Tri'rI T CAO 2379 HtJUAM2A 416 GUAAG3 LGAUGAG X COA ACCAU 2112 GAM=IG C CtCITrPC 2384 I~RDE.A2A 417 GaMG CGtUC X MA P33A 2113 'ITtTr T TACIGLM 2385 H]ZA 418 COUCG CMGA X C:A A13C 2.14 G~TCCI T .'CIA 2386 HtOX2.A 419 GCC~U CL3UA X COA AAO~ 2115 'T=tITrr A CIGA= 2408 HUMMA2A 420 CCt XWAA CU3ALr.Afl X OMA APDG= 2116 CiAIC r C TMTCAM 2410 HUInATA2 421 CACttA CUAUIXA X CMA AGAM 23-17 IGCI' T CIG 2411 HU 2 422 CCC CtLGUA X 03A AGCG 23.18 CrIGi=r C TCQ3I= 2413 HUMC40=2 423 GCAr U CUGtUM X COA AGkGC 2119 =tI TI~T C AOOA 2428 HUtaAT2A 424 GADCLI afLGAG X CGA ACIUJ 2120 ACtCA A AM= 2432 HMMM;2A 425 AA~fl~Ir CUWXUL3 X C:A ALUMOUI 2121 AWflMAML A CdAM= 2436 HJ11TM2A 426 AGAAAAG COGADM X CMA AIA=JL 2122 AAMGA C CrITI 2439 9242AMP2A 4Z7 AGCAAAA CLUMXCM X OMA AGMM 2123 7'GAr T TIWI= 2440 1UMM2A 428 tPLMGA CUGXMW X CGA AGGlJ 2124 AGtCI r T TIt'I= 2441 BLIUA2A 429 MVCG CUAL7GA X MA. AAAGCX 2125 GAi'r T WCIGIC 2442 RtJ!MMA 430 GULPDC7 CUGAVMG X CMA AAAPaW 2126 AITT= T C1GCM 2443 HI43'M2A 431 GOXP= CfLOMXW X CCA AAAA~ 2127 ~TCCirr C 'TGCA 2448 HtJD.'A2A 432 UGAA= CU2LM X CA ACLAN 2128 TIWIC= A AMC 2454 HOMMiTi2A 433 CU3JW C NXG X OMA AA03 2129 TAAC r T AACOA 2455 MUM=~2 434 CAGX7-G CU3AIXG X OMA AACXP 2130 TAG tIT C AIGt= f 2 4 74 j H UEA T 2 A 4 3 3 u 3 3 3 = n c t u tx x 0 3 A A = M 2 1 3 1 C iMA = T C IC I= 2485 HJI12MA 436 MAMMA CLWL X C:A ACCG 2132 GCI=r C ICAT= 2487 HUM.M2A 437 CMM= CULIGA X CXA AGO 2133 aiIGO r C AG1= 249 HU.=A 438 AAAG= trjo x~D co ~A am2134 WIA~ C CIACITT WO 00/61729 PCTUSOO/09721 66 Table IIJ. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 2499 hUMMA 439 CAATJA CO3MI X 03A PLIUCTX3G 2135 2TCCACr T ML=G 2500 htJ-ETA2A 440 GC~Z-.W cuLr)3G x a~A AGUCUM 2136 C~Ci'rM T ATGIGX 2501 hUMkT2A 441 AGakA CtGUX3A X 03A AAGtf 2137 CM=T A CIUIM3: 2516 HUGATA2A 442 UL13SAA C XAIXA3 x aA AUCX~CC 2138 CIGI13AT C CCtAA 2519 MMAr2A 443 ACtUtflX CMXAMAG X (GAA AGAtCA 2139 IT=CCl T CtCAAGG 2520 HUMT2A 444 UACUtfl CUflAWAG X CMA AAGAUC 2140 GGcrr C CCAA=I 2528 HUrMA2A 445 UAC= UGAUGA~G X C3A ACCU33 2141 MUM= A CAC 2536 HUM.k2A 446 CGJUUNI CtflWLG X MAA AP 1 GCLXJ 2142 ACI r A EATAAAX 2538 HUD-2A 447 CAM=~ CTAMU X COAA AMU=~ 2143 AGCUT A 7IAAITO 2540 HUM.'2A 448 GAAC3tJ CtflAUGAG X C3;A A1WiUCAG 2144 C=A A AAItI= 2548 HUMM.~A 449 A?,mi3 Ctx3Ar. X COA AMC=U 2145 AAA=~ C Cl't' 2556 Mr.AMVA 450 C.AAAUC CtXAIGA3 X CMA AGCUC333 2146 MCtM T AGAiTn 2557 MCAT2A 451 ACAGAAD aC3AMAG X CGAA ACUC3 2147 CCDZIT A GATIt'= 2561 HUM2A 452 GCMA CarALGA X MNA AUCEMA 2148 GU IO T MGM=t 2562 HUGk2A 453 COAUC CUGADGA X CGAA AAtt PAAG 2149 CI'ZAT C TIMMO 2566 HZMT2A 454 'UtAMC LCGUAG X C3A ALA 2150 GATtr A 'ITGT 10 HGA3R 455 GOGAUMO CUGAUGAG X CMA. AGEflfl 2151 ccG= T CCCTCC 1. R93.TA3R 456 G03:2=LU COGAMflG x a:PA AGO= 2152 CAGLr'r C CCt= 16 HGATAR 457 GGO CUIGAGXG X 03A ALM)L 2153 cTIC=T C CLICAC 35 HSCAM-R 4,58 CtJU13 CtEADUG X C[A ALJUUEJ 2154 AAGCAWI C ATIC 38 H.9GflMR 459 GGUC= aflAUA X COA AI~UGAUW 2155 CAATCT T CACP 39 H3R 460 G33UCU CUt XM x A AA1GAUXJ 2156 AAA~T= C AA ttCC 56 HSOM3R 461 tO00 CUGAUGA3 X CGA AG3C3 2157 CtCGAT C CAC3C 80 HS3AA3R 462 CC0 CIAtx:94 X CMA AGOCG 2158 -CC C AG0, 97 HGAT3R 463 '"IM UA~LM X CMA A03 2159 ACttT T CCI= 98 HMAT3R, 464 cmom mmumL x anA AAOCO 2160 CC3CCC C C=C 102 HRTAM3R 465 COC033 C JALGA X C11A AG3A 2161 CCTI= C CC330 114 HRaz=R 466 OOCOCGAU= X OMA ACCOC 2162 1 - .r T 11. 115 HSAT3R 467 03300 CJ3AILM X 03AA AACOO 2163 C30i'0 C C3C0 208 HSGAA3R 468 L130OU CLML X CGA AGAC3 2164 GC03= C AA33C 244 HSG.A3R 469 GAU CaXKiXW X 03A AG003 2165 C033 C .AGCC 252 HSC2=R 470 CCDU CLtGAXSG X CMA AGU13 2166 akoCr C MOM 255 HSAE3R 471 COUCCM CUGAUGA X CGA AGGAGU13 2167 CCACr A CA P 273 IH. IA3R 472 GCCn CrxwIP= X CGA A-UMC 2168 G3030 A CCI= 301 HSPMR 473 AUGEWA CUAxDi X CGA AMCAE 2169 GA7G= T TrU 302 HSCPMR 474 GUXM~A C MtXU3 X 03A AAGCAIJ 2170 A~TGI=F T TMAMC 303 RgCWMR 475 CAUInJM CLUGALIM X CMA AAGCC 2171 TrGii T TACA0 304 H~93R 476 L103AUOM CUPLA X 03A AAAGCA 2172 G0C=r T ACAC~ 305 HS31M~R 477 MOM=fl ctGAXM X COA AAAAPC 2173 'GI7M~r A ACATOMC 310 HSAM2R 478 MV-=~ an)AGA X CGA AVLMM~~ 2174 TM=T C GAGGC 317 HSGAMR 479 GJ~UU CUAU X 02A ACG~ 2175 ITCGLA1 C AAOCA 331 HSGMM~R 480 tWAG3G CLUMLA X CSA A03UmXJ 2176 AACCA0I' C C0CO 339 HSAM 481 mccmGajum xtlI X :; ~AG 2177 CtCO r A C MMA I342 H932R 482 Awatt= anViMG X 03A G 2178 COMICT A C3MACLT WO 00/61729 PCT/USOO/09721 67 -table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 351 HSCATA3R 483 CCLI)= C~r-;I).A X CC-A AJGTAX 2179 CGAAACr C GUItCAM 355 HSGTh3R 484 c..U3=CMaAMAGL X 0t3AA PACSJ 2180 AAC~T= C AG3C 375 HSGAwIA3R 485 U.COGa .r CMM K X 3A AtU= 2181 GCG~ A CCCICM 380 Kc.GAT3R 486 GYLUCG CMALUA X~ 0 3AA ?DGJ3C 2182 GGICMt C Q3ACtCCA 416 HS3AT3R 487 AMAAGM CtXAUMG> X CCAA AGGC= 2183 OCxCO C T~r 421 HSCT3R 488 GOAMf CtLr-ACA X 03AACGG 2184 CrMtI=j T CATrCXP 422 H.GATA3R 489 QOIfJJUf CUCAUGPG X OMA AACM 2185 CITITrT C AGC= 429 HSGATA3R 490 AGOOLM CaUXA X COAA ADCAG 2186 TCAGGT C CtiCM r 433 HSGTA3R 491 POCCAG CMALGA X OSA AGO=C 2187 G3AT A CWI1= 480 HSGATA3R 492 tLCA= CUMMrG X CMA PM3C= 2188 CAO r C (OCC= 491 H-lGTA3R 493 G33t3= CXMA X CGAA AUUCAG 2189 cCTOGAAT C TCG 493 HSGATA3R 494, AGOOUE CLIGIYIA X CCPA AGUtX 2190 'IGAAa= C AGCrr 501 RSAM3R 495 tUtM CLMA X 03A A3G331X 2191 CAGOcc' T =CAAGP 502 HSGATA3R 496 G~rUt)WA CUMMXG X 03A A003CL 2192 AGzttcr C TCGA 504 HS~AMR 497 ACL=~7 CLEAMAG X (IAA I~ACAC 2193 CtCiwr C CAAG= 513 HSATA3R 498 GSLIOAM U PM Xin K AA ACGUXU 2194 CAAGr C CATCt 517 HS A= 3R 499 CtC.fl3 CUGAUGXG X CMA ALaj .2195 A(CM=~. C CACA 528 HSGAM3R 500 X-M 3 CUGA[XiG X CMA AGC 2196 C~CAC C --MM 541 HGA3R 501 UAGALa CMAMtX~ K MA AG3 2197 G030I= C 'I003= 543 HSGA3R 502 GGLPCA aLXNUIGA X CA AC0 2198 GCxtwi C 03MA'C 547 H9GAT3R 503 G333 CU~n X 03A AC=Z 2199 CTCI=r C LTAtC 549 FASaThR 504 C33 Ct'GALtM x aA AG03A 2200 C7C=t A CCCC0G 561 HSCAM3R 505 AGAGC CUGUXW X CNA.AGCM 2201 CCOI' C G7OI =~ 564 HSAT3R 506 ALXA CtLXMG K A A~C3A 2202 G30Cr C cMwicr 567 HSGATA3R 507 ACAGA cUxmDl x aA ACA 2203 CI03IIM C CICCri= 570 HSAT3R 508 CCGACAA CtflAU X CA AGA 2204 G=wiw C CrIti 573 R9YX:A R 509 CtCCOC CIGAU= X CCPA 2GGAGG 2205 L:1 rCtr T GC33O 576 H.G'I3R 510 G300= CMfAIXPG X C3A ACAAGMG 2206 CIwri= C 0333 601 HMATA3R 511 AGG'CA CEGX2X~ K A AGGUG 2207 CCOrA C TirC r 603 HSk3R 512 GakN mmvmGP K crA AGGa 2208 GCACLr T CAri= 604 HRMM3R 513 GOG3A= CUAUGA X CtPA AAL~Lfl 2209 =cit' C AC= 609 HGA3R 514 U== CUG~tX2G X 0:A AGL1AAG 2210 C77CA= T C03X 610 H3GAM3R 515C L30 CUGAUMG X CCA A03IA 22.1 TIAT C C3CA 634 HSGA3R 516 UC33! CLMXw7G X CA AflOfl 2212 AGGwr C TCOO~ 636 HS~.TA3R 517 GOx)i= KTGAM X A A 2213 GGM1C CC03A 648 HSM=AR 518 PAZ= CarAI= X 03A A== 2214 GGAI C GC~rC 654 HGA3R 51-9 MOM=l CUAUMG x aA ACGO 2215 ATCOI= C CAM=~ 666 H9M 1 I3R 520 AGO CLIGAM X OMA ACtEU 2216 CtC I' C 3 = 6"75 H.!E3R 521 003=C UaWn0L K O:A AC 2217 GOOO C 13C 703 HSG.a3R 522 t cUOGU CL'GUXMG K CZA A0CAU 2218 GAGI=C C AAMC 708 HSC3R 523 G~tk= CGAU X C:A ACUJGA 2219 Ct'IAAGI A CAG= 744 HMAT3R 524 AGU33C IGUCMX K MA A.LT= t2220 GCGG~ C GCI 747 RC;3R 525 GCA=n CLGAA K CCP AC 2221 GGAG= C CCCW 753 RGAR 526 tflak a) GUI X A AaXM 2222 GFttt= c amaI WO 00/61729 PCTIUSOO/09721 68 Table III. Hammuerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 786 HSGAMUR 527 UCGACGL OflUAG~ X OGA ALXCUCCA 2223 TGCAG=r C CwICGrS 789 HS3TA3R 528 GOG= CGA M X A1G X 0MAM= 2.224 AOCCI=~ C G=-,AtC 792 HSOAUA3R 529 cGnxU z CMMA X CG@A ?AGA 2225 MCC=n~ C GACCACC 808 RgGA'.3R 530 UkGG= CXMAA X ctMA 1'L333LI 2226. CACrt'-! C LACCAC 816 ROGATI3R 531 ADGG3 CMAMX~ 03A AGGfl 2227 CXA=C A CtO3r 825 HSGAh3R 532 C333CG CLr.A= X CA AGl33C3 2228 CrCtCr A CItrt= 837 HRcA!A'.3R 533 C DG~aX CMAMA~ X CGAA ACL= 2229 GtttGAr A CAGC= 843 HS3GI7MR 534 MPJG CMXAIlAL X CGA AOCU=~ 2230 GrArAGr C COSA=T 850 HSAMR 535 G03)33A CtXMAGr X CGAA ?AGUCO 2231 'iC~C3r C TICtCt 852 HSAMR 536 U33 CtXALMS2 X CCAAG 2232 ~COGCmr T CCCCCtC 853 RSCA2R 537 CUf332= CU7-AIM X OA~A AALGAC 2233 GSACI C otttO= 879 HgCAII3R 538 COGL3 CUMMAG X CMA AGCtt 2234 cx30 r C CC0L 891 HSA2%R 539 tlUGC CU3-AII X 02AA AGCZG . 2235 (CALC= T C3A 892 HSG~kR 540 UtXXOLt CMA3GL X 03PA AAG'CflJ 2236 ACIT C M3AMMA 903 R93AZ.3R 541 t =3XU CX17)GX~ K cA ACUXrAJ 2237 AMA~ C CAO 921. HC73R 542 CUGf3 CMfAUIX CXA AC03 2238 GxttG= C CACA7 960 RIMR 543 cX~x CL13AIGA X 0A.A A==~ 2239 G(CALtT C GACtt=f 996 H~I3R 544 tDMCAL3 CAnXMG X (XAA ALGtCC 2240 OOMALr A Ct'IGMA 1018 HG3R 545 tmnOUMM CtX;V)lC-A X C A PGCCA 2241 1roG= C TANIXA 1020 HOAVR 546 UUtUGnXA CL!GUA X 0AA AGGO 2242 CG33 A TCACAAA 1022 H9CA=3R 547 CMLRXXXYJ CUAUA X CCA ALGA 2243 GCICM~. C ACAAAM 1051 HSAM 548 GUtLXMM COMMAL X CMA A30= 2244 C030= C ATV= 1054 HM73R 549 UDXX3W CUMLIGA X OMA AUGA03 2245 CrwIC= T AA~M 1055 H.SL'Th3R 550 CrUG CtGAUM X Cat AAGAM 2246 CCTCIATr A AGCCA 1074 HSrAOR 551 UnxaxrA CUAnUiA X CGA ACAGtIJU 2247 AAGIO r C TGCA 1098 H~'Th3R 552 UCGACA CUAUGA X CMA AGU 2248 A003A C CIUCI 1112 H.k73R 553 GGXUG CfLUIflG X OMA AAGUU 2249 mwiaCI C AGL 1132 HGAWR 554 CCCUtC C XMIML X OA AGHLG= 2250 =A=c C TGAGA 1162 FH.WThR 555 GCLX0 CUGAM3AG X OA ACG 2251 CAO= C TGAA 1180 HSGA3R 556 UtflMm CUMYLA K CMA AGOCU 2252 'IVI= C 'U~nC~A 1182 HMMR 557 GCULIOIA CuLIGAGA X CA AGAG 2253 'IGItT A CICAG 1.185 FHI7M.R 558 GkAtt=f aXWXmG x CXAA mm=L~L 2254 GCIC= A CAG 1192 HSM~3R 559 ALnPIX0 CUGAUGA X OCA AGUU~ 2255 TAAGr T CCA~T 1193 HMAMR 560 AAfltfl CUGAUG X CGA A3AGXfl 2256 AAAGT C AA 1199 HSGAlr3R 561 ttfLGtUA CUGMDyW x aA AIUXXA 2257 MrCAAT A TMACAGA 1201 H9GAMR 562 GOLrl-= CU2UMG X 03AA NPLDtflf 2258 CACAT T AAC 1202 H EG MR 563 GOOU= cu~tA x aA AAEMI= 2259 ACAA=T A ?A~CAC 1217 HSAMR 564 CUUtnUtm CLt7-49flA X CA AGCC 2260 Ct'CItGL'r A IGAAA 1234 HSGAM3R 565' CmUGG CUAUA X 0A MC=U 2261 GAG C CAACA 1257 -SCP=R 566 AfLXXE CGALIMG X CGA AfltUWUU 2262 AAAAAIU C TAAAT 1259 HSAMR 567 GaArX13 GflAGA X CA AGAAUUU 2263 AAA2It A GCAA= 1266 HG3MR 568 Acuuuutn CM4UXLG X 03AA AXXI= 2264 IGMAAT C CAAAAAG1 1293 HRGXVR 569 CCLrxCAG CLu~riP X CA AMC=if 2265 GCATUALT C ANCIGM 1305 HGM3R 570 tttafl2 CUAG X K : ~Aar=~tL 2266 (XmwLT T C 'ilk~ WO 00/61729 PCTUSOO/09721 69 Table Ill. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1306 H-Ir.7M3R 571 UtUtUt= CMXAMfl X OMA ALGU= 2267 GAAGGrr C CCCAA 1320 HS*XT3R 572 GGUtMAAC CUAfLr-x1r X CCAA AZJtX 2268 GAAAGr C crrrACC 1323- HSAT3R 573 CCJE= CMfl.Lr-L X MIA ACGAt= 2269 CAOIC= T TAACC3 1324 HSGATA3R 574 OC~3EJ CMX3MAlG X 03A AACGGU 2270 AGICrr T APAtC2 1325 HSGTA3R 575 GtC= aflAMAG x CAA AAAG13 2271 G'It1IIT A ALCCCOC 1339 R9SA4.3R 576 MUMMA~ Cr.UGP X CC@A A0300 2272 OCCtOt' C TCAA 1341 HSGAMh3R 577 UfLflX;= CAMaOi X CGA AGG 2273 CCCttw C CAACC 1353 HSGATA3R 578 LrAGW C!XAUXG X CSA Ptflfl 2274 ACACAI~r C CItCI= 1356 HSGT3R 579 GOCU= CMfAMAlG X 03AA AGM= 2275 CATU=~ C CtIGGC 1369 RSGAT3R 580 A1;3 COGAUGAXG X 03A ALUGJ 2276 AGCAA C TOICCIT 1371 HSG.Th3R 581 tLrAA=2 CU3-IflG X CMA AGLflfl 2277 CXAATI' C CXWI' 1377 HSMM3R 582 AGl22f axMix X CMA AG0A 2278 CItCGr T CAGCCAT 1378 HGA3R 583 GAU J CLXI.z X COAA AA3= 2279 1tCIT~r C AGC 1386 H92=R 584 tftUG 3 CIALMG X 03A AGJ03= 2280 CaC3CI C C;CCC 1428 HSGA~r3R 585 ACG f Cfl)Ifl-A3 X CSA 2IU3 2281 CC3= C CCT 1437 HCP3R 586 GUCCAAAG C~LrDA X CMA ACA2tX 2282 CAGCr C CrrIW-A 1440 HG3MR 587 MOO= CXX4UGA X CGAA AGGC. 2283 CC~IG1Cr T 'IAC 1441 HGAT3R 588 tfLmflz CMALU.tG X CA AAMUM 2284 CIUIWI T GUC 1458 HSMT3R 589 CCAI!f CLML~ X CMA A03OC 2285 CC1OT C CACA 1468 HSAT3R 590 ALUflCJ axMrx X OA ACtAU 2286 AGCXAI C ACCG= 1481 HG3:3R 591 AG33r=YC CErAMnG X CGA AMC 2287 crA'IUr T AGG 1482 HGAT3R 592 C2G = C~LXPG X COA AACCCAM 2288 alm=I A GGI= 1493 HSG!E3R 593 tnGA r CUGAGAXP K CA AGDA= 2289 QGICI' C GAG 1500 HR3kT3R 594 .ttl " UCUA'A X OA AGAO 2290 TCGA C ACG 1521 HSGTA3R 595 ACU3 CLGUC;G X K P AZLC= 2291 OOwP C CCIGa 1530 HSCP=R 596 tCAAAD CtGALUA X OA ALU3=L 2292 rCIG= C ccrir= 1534 HSAT3R 597 CAGUM CLIMLtP X CGA AGOGUG 2293 (AGT=r T 'ITCI'I 1535 HaT3R 598 C2AAGJO CMAMXAG X CA AAGO=~ 2294 AittIC r T = ='I 1536 HSkI3R 599 tLIXar CUtGtflGL X CA AAG3A 2295 G7CCrr C ~C.IM 1541 RSAT3R 600 AAAAU(3lC cum=P(. x A NAOAA 2296 I1=L T GCT=~ 1546 HgC3R 601 CCLAAM CLXPL X C= AL13AAGJ 2297 ACI=T T TrICI3 2547 HSAMR 602 tttUOCAA CUAUGAG X OA AAGCAA 2298 CrIT T TIOGO 1548 HSC2R 603 CtLXX CMUMG X CMA AAAIGA 2299 TIM=ar T TOAM 1549 H9CN3R 604 GCUOtt CLIGL'M X COA AAAAI= 2300 1= MIT T GCAGMWP 1561 HMMR 605 CL1Axik CUGAL'G X 03A Acti~a 2301 GGC~ A ICTGA 1563 HST3R 606 GOJrEXM CLPI7 X 03A AMC='t~ 2302 AGA C ~ATGMG 1573 R9STA3R 6017 At JtJ CMUIA X CA AGCUA 2303 'IGA= A AA030GT 1586 H9MM3R 608 AAAAPALI CLXGADM X OSA MOM=X 2304 CGTGA A 1A.TG~T 1588 H:; R 609 CAAAACA CLt7ALXPG X CA AIUIJA 2305 ATIMAM. A rI==i 1592 HM3R .610 OurXXAA CMw ~ X OA ACAUUMI 2306 AT~k= T 'TICA 1593 H3UR 611. GCtUUtA CtIGALUA K CA AAXP.EAi 2307 MkIT T TIM= 1594 1tOAM3R 612 tUGtrA CLGUA K OA AAACAUAWJ 2308 ATArrr T TGA 1595 NH.Th3R 613 acuc cupwxwG K a3A AAAC 2309 MM=i T GAG 1614 RsP=R 614 GMAA an=AG X CA AzuUE= 2310 -1 AAAAT T AMIGT= WO 00/61729 PCTUSOO/09721 Table [1I. Hammerhead ribozymes targeting U 9 ATA transcription factors (1, 2. 3, 4, and 6) and the complementary sequences 1615 HSC2A'T3R 615 GGAAACA CUXAM7Pr. X CSA AAIUtX3 2311 OAAAATr A T~rrc 1619 HSCA'I3R 616 AG33= CtM2.ID3G X 03A ACAL1tLAJ 2312 AAM=~ T wOCArr 1620 H.SAA3R 617 AAGL CGAtfl X CMA AAIALIJ 2313 A=TG.= T O~CCA r 1627 H.92A'T3R 618 CCTU= CLUMG X CGAA AGU03CA 2314 TIUC=2 T TGOAAD 1628 HSCA'T.3R 619 UJCCUUtOt CtXA1GIG X 0AA AALX~ 2315 'IGC= T GCAA~ 1640 HSGAT3R 620 ACCA CtLr-At.P X CIAA AXICUU 2316 AGGA= C ACG=~ 1651 HSAT3R 621 03AACAA CLM A X CGAA ACCAA 2317 MUG=~ C TG7G=IC 1657 HSGATA3R 622 Gfl23 CMMA X COA ACCGC 2318 MrCI=i T CCAACC 1658 HSCAMIhR 623 AflUJt) CUGAMWC X OaA AACCAG 2319 ~MIGI' C CAA CI= 1671 HgMII3R 624 0333OCA CtTJJAL1G X CMA AUUrC= 2320 CIAMT C IGGAC 1682 HC-AT3R 625 UAUntAC CCAIM X CMA AL0300M 2321 M~CC=C~ C TGIGAATPL 1690 EgGTAR 626 G~A~U CMALtW X CGA AUUCAA 2322 CIGIMAA A AOTCCA 1697 USSAMIhR 627 MXAWMG COCAL3A X 0:14A AfL03CLX 2323 MNAGT T C17.CI= 1698 H93Aa=.R 628 AAUCA~ CUGAUGA X COAA AAItXJ 2324 AGTr C 7tGAC 1704 HSGATA3R 629 GCAUW CUMAMAG X CGA ALX~kGA 2325 Tmw'Icr c ~Au= 1707 HSAM3R 630 A1JAG33 aflALU X CGA ALM=~ 2326 ~TGAC=~ A MM=~z 1709 HSM=R 631 AAAI~kXX CUMA X CA PLULUGG 2327 ACIATT C CtCICTI 1714 H9GAaMR 632 CUGLPtAA CtMAMA X CMA A03A 2328 ~TTCCt'r A TMM 1716 H-SJAR 633 CCtLU=U CMlAUC-A X CGAA ALMCX 2329 WCW:AT T MkAC= 1717 HO3MR 634 ACCCUGMt QflAUGA x alA AAAG33 2330 CtCCC= T AACAT 1718 H.AT3R 635 GAICUGU CtMAUA X CmA AAMMOM 2331 CCMTITr A A C 1726 HR~kT3R 636 GAT-PGA CUYDC; x alA A~ttLCCt 2332 AAACOT C ICGI3 1728 H.g'TA3R 637 ~CGACI CU,-AMlG x a!A A~kCzO 2333 CA03r C 7IG7= 1730 HSGAT3R 638 CACAGC CtLEAtA X CGA AGAGtt 2334 GO=i~ A GGC=I 1751 HMM-R 639 ALLXMG CXGt7GAG X CMA AUJUUUtXJ 2335 AAAAAAT C CGAACAT 1760 HMA3R 640 UtmUU]n CtUir.A X CGA AfL73UCA 2336 CItGA= T GI'AA 1765 !{RTh3R 641 AAWE CUMUAG X OA ALIOAfl 2337 CATI=T A TAACI' 1767 RH3 R 642 ALUAG CrVJA X OM AtPLIXM 2338 7'IMTAT A ACrIB= 1771 Ha~AUR 643 UACAIAIJ CMMA X CXAA AGLXMLPD 2339 ATAMhPrr T ATAIGT 1772 Rk3R 644 ttAAIP CUflAGA X OGA AWJ4PM 2340 MkZV A TIATM% 1-7-74 HFi-Th3R 645 LtL!X[A CUAUGxG x aCA ALMA=XI 2341 TAAC=I. A TIIAGL6 1776 HSrA3R 646 UUUmCUA CLGLIP X CCA APMAGJ 2342 ACTrAZT T GIBUWA 1779 HSAT3R 647 _GMEnJ CLIA2GL X OA ACMW 2343 TAIATr A AA 1786 HS.kq~k3R 648 ULxnACA CVAM X =A AUtX)tLtl 2344 TAPGAAAT A CIMMA 1791 HRGA3R 649 AGLNw COA~UG X OA ACALMM 2345 AAMLICr A CAT= 1800 HSkrA3R 650 AUGCAIM CUAUGA X CCA AGUTJW 2346 CATGCr T 'ATI=a 1801 H.AM3R 651 CAL3A! CUGAUGA X CMA AAGUXM 2347 AAICCr T ATG= 1802 HR3MR .652 ~fAGAOCA CLIUMI X COA AAAGXCU 2348 ATCIT A ''~c 1804 HGr9A3R 653 CCGA CLICAUM X CIA APAAGUt 2349 GCrCI=. T GOU 1809 HSCAMR 654 GaM= CXGAUGAG K 02A AE=A~ 2350 TAT= C 700G= 1815 ,H9MMUR 655 CUE.A CLICAGA K CGA ACCAA 2351 ATCI=~ A GCM7AA 1821 H.&AMR 656 LrA~y UGUA X~t K A ACGCA 2352 GnY]= A AGCA~ 1845 HSCAMR 657 xw= anwmG K aA Aax=tIf 2353 aWAAM T MAMWA 1846 HSG!I3R 658 uux=c muu A x~ a3A A~VtLxJ 2354 A~fAC IT T AAGGAAM WO 00/61729 PCTIUSOO/09721 71 Table 1Hl. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1847 H.S.Th3R 659 AIMUU=t C!XnLXA, X CA AAUtEU 2355 ~AGT= A A~kT 1854 HSGATA3R 660 UU=tt cIIWGL X MIA At=tt Jt 2356 MhA~' A -, AC-z 1865 HSC2TA3R 661 ULIOCACAC C~AM3Afl X CGAA AUtXL= 2357 GmJAWA A GG7GA 18716 FEE ATA 3R 662 UUCLrtJ C~Lr-AIJ3A X OGA ALKX)= 2358 GMAAAT T AAAA 18-77 HSGATA3R 663 uutrut ctrAtflG X OSA AAIUtt= 2359 TGGAAT1' A NIAGAA 1888 HSGATA3R 664 AUCAGAC CtrUGAGfl X CCAA AGUUU 2360 AAVAC1 A GUM=l 1892 RgSkA3R 665 GAA1F4XA C~tLGALP X CtMA ACCUAJU 2361 AACMCfl C WTM'I 1897 HSMTA3R 666 CULJXrnA CMUAG~ X OM MA=E~ 2362 GUM=~. A ITC~AAAM 1899 HSGTA3R 667 uczuutx mrmAtGL x CA AAUIAG 2363 TIGTAIT T CAA'IG 1900 R92AT3R 668 GCCUUJ CUGAUGAG X CSA AiAUCA 2364 CiMAMr C AAA=AC: 1920 HSGAT3R 669 0AAA 1 CAA CUflAUGAG X CrIAA AUA 2365 CTGCAr T 1113-77ri 1921 HSGATAJR 670 -AAMCA CMtAIA3 X CtPA AA t= 2366 TGCIT T '110T7WT 1922 HSCA3R 671 AAGSAAr_ CiGALrp x c3A AACL=f 2367 GCCArrr T GrITICrI 1925 HSCATA3R 672 tWAAAA CUAMfl X CGAA ACAAALU 2368 AGTI'I= T RXWITIM 1926 H93iA3R 673 GuGAA~o CmfAmzr3 X CMA AACAAAC 2369 GrrIur T ccrrMirC 1927 R3GAI3R 674 ~AMA CUGAGA X CCA AAAMA 2370 Tr rr C CrrI=c 1930 HSMM3R 675 GCAM CtGVJG x a:A AGAAC 2371 'tUTr T TaCI= 1931 HS3G.TA3R 676 MCMIX aflAUGA X OM AAGAAAC 2372 Grir T CAT 1932, RSGATA3R 677 uo3aj CM1 I X CCA AAGGAA 2373 Trio=rr c Am = 1945 H.MT3R 678 C1AAC CLtGtflAG X CMA PAUCL3G 2374 GaC==r T GriTIm~ 1948 H9C3AT3R 679 ADG CIMUGA X CGA AOG=l 2375 AMGri T MAT 1949 HSAT3R 680 AZALUAUC CfLMUNG X OMA ACAa 2376 CAGT=r T GAG=T 1957 HG~r3R 681 UtLXtJU CtU.EXAL X CCA AUGAX 2377 'ICA7= T AAAAA 1-958 H.kWR 682 UUUUUUU CtXAL X CXA AAIOCAUCf 2378 GAG= A AAALGAAA 1968 HGAT3R 683 axxuttJut arIXM X CMA AUUUtMUtX 2379 AAGAAAT A AAAAAA 2009 HSGAT3R 684 Lro=]WC CUWGA X OMA AaXUtJ~X 2380 AAAAAAGr T GkG 2012 j HSCAMR 685 GfLXI=CL ctx AG X K A ACAC!XX 2381 AAI'I= A GOXI= 2020 HGAMR 686 GACAAU CUAUAX K AA ALX1030U 2382 Jd'M C AITM=~I 2023 HSAT3R 687 tXJTACA CUGU)3X~ K AA AUJM 2383 OSAA=I T TGIAA 2024 HR9MTA3R 688 a~xxi ~ CLIMXP K MA AAIXWX 2384 GA'Ia T T GICAAAG 2027 HSP=R 689 @ctw= ctu1XG x ~aa Aw 2385 TW=~ T ~aWI 2028 Hs;=R 690 ACXX3 cUU UL K~ ~~Af 38 TIIrCA~~ 2037 HgMM3R 691 AGAG KDAUA X M AAOLIU 2387 AAI r T G= =~ 2044 HSC23R 692 CLTXXIO aCLA X 03A A03M 2388 TI3= C TOAA 2057 HSA3R 693 AGACUfl CUOAUGAG X 0:A IAUUtX 2389 AAMA A CCAGII 2063 H9G.ThR 694 Ltj3r CUALIGAG K aA ACU]AU 2390 ATC T CI30A 2064 MSAT3R 695 ALWXIOCCM CUGAUGAG K CMA AA~CtLI3 2391 'ACCA1T C I3CAT 20-73 H3AL1IR 696 GpLULOC L7GA2 X CA AUt= 2392 TG33CAT C A GM=~i 2079 HSCAT3R 697 UGAC= aimumG x a;A AaCUMI 2393 ACIA r T PA I'1M 2080 RHiCi3R 698 PgkC CGALr4 X COA AACtGA 2394 '1CIG= A C3rI= 2085 HGA~I3R 699 AALtOGM CL-A K CA ACPJC 2395 GI

T

=I T CACC'r 2086 N3MAM3R 700 CAAU3LJ CUGLXUL K CA APOGA 2396 TAI C ALC It3 2093 RHiA3R 701 LrAMtM CLVJA X 03A AMM 2397 'iAC= T GTM 209 R9 R 02 ~ )ttU O t~ ~ At~P~ 2398 GI T T @G ri'r WO 00/61729 PCT/USOO/09721 72 Table Ill. Hammnerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 2106 HScGATA3R 703 CUM=1~ CMXALMJG X 03A ACCCCA 2399 TIG=T T TCG-A 2107 HSGATh3R 704 GCUC=tt CUGAM X CCA AACCCUXA 2400 'IGPflGI T aVGG 2108 R9GA!EA3R 705 GGtU CU2GAMAG X. - A AAAC=t 2401 C~AG3rr C AGGAC 2118 H9GATA3R 706 CCtU&G.AA CUAMC X CMA XC3C=~~ 2402 GAGA T ITICM 2119 HGAMR 707 OCLII.AA CMfAMflG X CMA ALX)U 2403 ?P CIT T Tt'I= 2120 Ha3R 708 GOCCU7'L CMAMA X O:A AM =~~! 2404 GAWTD T WTCL= 2121 HSCAaM.R 709 AGOttU clr.,AinJ X 03A AAA= 2405 AGCIT T CTDX= 2122 HS3ATA3R 710 UAO CtXAiflZ X CtMA AAAA= 2406 GCm'rr C TAO 2124 SATA.3R 711 UGLV= CAMxIAG X CCMA AGAA 2407 =ITIICTI A GCtCMMI 2130 HS3ATAJR 712 AAAPCALr- CMAtfl X CMA AGOt!JN 2408 CriAGxc A CATGIT 2137 HSGATrA3R 713 tlU C CUMAMfl X CXMA AtA 2409 'ACA r T IGrAA 2138 ESMT3R 714 ULTMlJEC CGAUGA X OSAA AAGCLJ 2410 A.~IT T GItAA 2149 R9SAR 715 AUVC CQEALU~G X CGA ACULIGUM 2411 CAACAr C Ct'IGV 2155 HSGAMUR 716 ACAACAAI CT2XMIfl X CMA AA03C 2412 GI7IT3I A ATI7GIU 2158 HSCAMhR 717 CAACAAC CXGAtX X CMA ALC 2413 CtTGT~ T GTICrri 2161 HSPM~R 718 AXJACAAAC CflAtfl X CMA A1XM 2414 GTrAT1= T Grl=~ 2164 HSCAM.R 719 LMCALTACA CUGAMtX. X 03A ACACAU 2415 ATIG=t~ T MnU 2165 HSk2AR 720 AIUVXIAC CGAUGA X CC2A AAACA 2416 TMTr=r T GBM'MZf 2168 KSC2M3R 721 A1JtUIM CMZALXAG X 03A AA A 2417 TIGIT1= A TGTA 2172 HS 3WR 722 UUGAULWA CfLrAL= X OMA AALPOA 2418 T=G A TAA'ICAA 2174 HSGATA3R 723 CXtLMAAU CMUA X CGA AIUA 2419 Gr9U= A ATICAA 2177 HSGAMR 724 C~UtL CtflALX X CGA ALXI~tP 2420 IGYTA T CAAGC 2178 R'HSAI3R 725 GSUJUU CUGAUGA X OCA AAUUAUAIC 2421 GITM;rT C AA1CAC 2192 HSGIAM3R 726 tUtULru CLIGA=X~ K A fLtXX= 2422 ALC.AAAAT A AGAAA~k 2204 HS~TA3R 727 AAIJPIAI CU~a X CCA KAM=XJ 2423 AAGT A GATr=.T 2208 HS~ 1T.3R 728 AIXGAAL CtLIfl X COA AIUPIM 2424 AIGAGT T ~TIr 2209 HSGTA3R 729 GAUMA U ~rlg K X OA AAICM 2425 TGU =T T ATII= 2210 H3Si'T.3R 730 tIGIflAAA CMXA=X~ K A AAAttIA 2426 GAGTI A TICLI 2212 HGAR 731 MM G CMAUGAG X 03A ~IAtMAU 2427 ~AAMAT T TATA 2213 HSGA3R 732 AU1M)M MGM=XP K CA AALPIAAUr 2428 = WrI.r T C~X 2214 HSGl!,3R 733 AA1VL'MJ CLEXWAXt K MA AAAUAPAAU 2429 ATFr.TI C A ICIT 2217 HSSATA3R 734 UAMAW CPUGUA X~XP K A ALAALI. 2430 MT=. C A7d'= 2220 H9GA3R 735 CUGlLIA CLtX2 G x a:;A ADGAUGAA 2431 TrCAT A Tn7AM 2222 HGT3R 736 GfLCLPfl CUM'=2P X CGA ALMIM1M 2432 C~TXflM T AACA 2223 HGA3R 737 MUMMA.J~ CU~aXMG K COA AAUAU3Wf 2433 ATA A TNM 2225 HGA3R 738 tUC7JJ3 CAM-AG X CA ~IAL fl 2434 CAThTI= A CAO 2239 HSW=R 739 AUrUtAIAC CMIflAG K CGA ACAGUfl3 2435 ~CA r T G30MAAT 2242 HSA33R 740 UPAfltUtk CUGAU= K OMA AAAAG 2436 ACI~IG= A TAAT= 2244 HGA3R 741 AMAAAUU ammw K CaA AU~kC 2437 TGI A A~~T 2248 HSGATA3R 742 AGMA~ CMfAL~r, K a!A AIXXMI 2438 GIMMAAT T VaTI'= 2249 H9GAM3R 743 C0AAAA CIflA K CGA AALXJLWIA 2439 TATAAATT T ATI'ICIG 2250 H9GAMA3R 744 aGAAA CLUMMG X OMA AAAMXXWf 2440 ATAAATrr A TYrI= 2252 R9-AT3R 745 GMC CMAUGAG X 03A ~IAAUUiJ 2441 AT T 'VCO 2253 H9MMR 746 CiU xr MGM K CA AAUAAXJ 2442 AATrMr T AWIG1 WO 00/61729 PCT/USOO/09721 73 Table 11I. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4. and 6) and the complementary sequences 2254 HSATA3R I 747 ZLAMA CtLMAG X 03AA AAL~AA 2443 AIATIT A atUCr 2260 HSGAThJR 748 CTAGAC CUGAMflAL X CTaAA ACfJ-IA 2444 TrAziCz A G~T'rMA 2263 HG3R 749 GxUt.WA CGAUGAG X 03A MMCA 2445 ai=r~r C TMAC 2265 HS'-'ATA3R 750 CaGjtCUU CUSX2.OZ X OMA AGAMM 2446- ~GI T AAVCI 2266 H.9CAVhR 751. rGJtD aMUGAG~L X OGAA AAGACUG 2447 cmrm rI A AGAA= 2276 R9S A3 R 752 AMGA CU3AX~ K A AOM=X 2448 @kACI= T =rT=1 2277 Hs-.TA3R 753 AA3AAG fLr4A X~ K (A AAGCAC~JU 2449 AACI='I T CI 'I.L. 1T 2278 HSMTA3R 754 ?AAAAA CU3MIA K CSA AAPGCAJ 2450 AC~TGWI C 'rT~IT 2280 RSAT3R 755 pr~A~cA c~ALrAG x o3AA AAA 2451 W=rICI, T TM=rI~ 2281 HS~kTA3R 756 Aw wwr.AG x cia A~LaAm 2452 =irci r T CMITI= 2282 HSCATh3R 757 AAAAAC CMAUCX~ K AA AAGAAG 2453 CI'tr C GTI=I 2285 HS3MR 758 ~APA CAMLnG X COA ?ACAA 2454 TCrii T I= =~ 2286 HSCATh3R 759 AAAAC CUAMAG~I X tZA AACGAAGL 2455 CTI= T GI''rIT 2289 FSMTA3 760 Ut--AA CUGAUCA X 03A ACAAC 2456 'ICGTI= T IGTI=A 2290 R93~a3R 761 AIUtfAA~L fLALr.AG x o3A AMNAAM 2457 CtUIT T GI1AAT 2293 HSkI3R 762 AAIXIXM GfLTAt;3 x C:A AMACA 2458 = 1 TII7 T TAT= 2294 HS1DM3R 763 AAMMf~iXmf cJraLr.G X 03A AAMAC 2459 TT T CMM=TI 2295 HSA~3R 764 AAAAmuIU cmurIf K amA AAzAA 2460 GTiGI c Am=irI 2299 HSAMR 765 AAMA CvauI x c:A AJCfAAWC 2461 arFicAAT A Trrrli 2301 HSM.A3R 766 ?AL3DCA CMr40xAG X 03A MAMMIA 2462 T1'CAA13T T TMttt=I 2302 HSAM3R 767 GA .G CMUIAG X 03AA AAMUMX 2463 TAATAT T 'iCCri= 2303 R9GA3R 768 ~A 1A CUGIW3 X CaA MAUALIW 2464 CATMT T ccrir 2304 H93T3R 769 GAAGA CLK29JG X CMA AAAAUAEXJ 2465 AAT= C CI'tIC 2307 HGAMR 770 UMAA arAUAG K CA AGAAAJ 2466 ATrrI= T MCI=~I 2308 HS~kTh3R 771 UUAGG CADUxG X CCA AAGAAAA. 2467 =rrirr C TCIt~IA 2310 H39..TAR 772 AAIJWrfA CXALA X OMA AAGGA 2468 T'rwiw c mmIAATr 2312 HSGAM3R 773 AA-AAIJG CGOGG K CCA AAG 2469 cciW=t c TcATrrr 2314 HMIM3R 774 CI.AAAAJU CUAUA K COA AGGM 2470 rrICI=I~ C AATI'I= 2318 H.k3R 775 CAA)GA CXL4X~ K NA AXP 247 CTICAAT T TICI'I 2319 HMMR 776 LTAC CLIMUKAG X OM AMMIXAM 2472 TCTCATr T T039= 2320 1H93MR 777 txwpm anIxmL K o~ AAaMLtMG 2473 CTraT= T MrGA 2321 FOGA3R 778 AUAAC Ctt=GA x1 K AA AAAAIUflA 2474 MIAArIT C CM7I9M 2325 HSMMR 779 GUXXWIr CUPOGAG K CMA ACCAAA 2475 ITrIC= T WOMAC 2330 Hs&m3R 780 AL~p=J CawuG x cmA Amr~AM 2476 GM7AAT A AXCIAM. 2335 FM M~R 781 AUMAM aCt~oAG K c A A Gj"MX 2477 AAMA=C A GMP 2339 H93AA3R 782 CXIA=l CtXMIflP X CCA AVPXM 2478 AAECkGA T AATC7 2340 R9M;3R 783 ALIXMMf cXXPD~L3 K aA AUIMM~ 2479 ACMIT~ A aM'iM 2344 RgCP3R 784 ac3cAA= amcw-l K pA AU.a= 2480 I'ATM T CAr~: 2345 HSMMAR 785 ut.cAtJ cu.oIXw K aA AAUWD 2481 AT T C I'I 2349 HSMT)MR 786 UUErj=t ctXiGAL K OA ACMAAM 2482 C T 1AA= 13 HLZCATA 787 cQ2A=Uf CtX2.uGG K aPA LUXXXM 2483 CCAAAAT T @CAiTA= 14 H143ATA 788 ccAIJom c~~imuG K CmA MtAULUfl 2484 CAAAA Tr C AAATI= 19 H1CA 789 AAAAIflCtC OXpjX- K o~A .AuUrfAAIJ 2485 M'Ir.AAT T G3=IT 25 , MCAMA 790 CU GA c~a~r.A K o:A ALtU 28 ATIGOMT T TC0tA WO 00/61729 PCTUSOO/09721 74 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3. 4, and 6) and the complementary sequences 26 HICAMA 791 AMC=X~3 CtMi X OSAA AALCCAA 2487 FLGnGa T wCCGGPr 27 HUCIAMA 792 UACLTrc CUGl~LAG X OSA AAUC= 2488 'IThrA T CCG~1iG2A 28 Hir~am. 793 UUACtG CMOUGIfG X C13A AAAAttC 2489 G33TIT C C33G7M 35 BUW!vTAA 794 CLtIflUtJ CMAMA X CGA AIKC33 2490 TCCGGGr A AAAr-r 47 HLICATA 795 ??AX3O1 CM1AMAG X 03A PD32rC t 2491 AAA A GCAW= 55 HUMAThA 796 ?JALMAA OCIJAMA3 X C:A ALGUO J 2492 ACtUT T TGI 56 HI1MMN 797 CAijtnAo CnUC4JP X 03AA AAGOc 2493 nAG rr T GICAAM 60 HUr-A 798 CCA t CAM~A~G X 03AA AA 2494 U-1rIIQrI C AA IGI= 71 HUCATA 799 JAC(G~UA CUGAMAG X CGAA ADOCMA 2495 'GIGIGAT T T~AA!Ar 72 HEW-ATA 800 U~A3= CMflMIX X CSA AUCCA 2496 CIWZa~T T AA AM 73 HUM Th 801 AMCW CMAMAG X 03A AAACCA 2497 CI70G= A ATC= 76 HIC-AM. 802 tALI= COAL X CXA ALTUtAA=I 2498 GATMAT A 03TT so RMUM 803 AAAGUA CMA=i~< X CCPA ACGUAL 2499 TAATACGr A ThA.TrIrr 82 HUMAA 804 tUAAAAL~ CrAGA X 03A AMC=1~I 2500 ATACMAI A TAITrA 84 HI.XA 805 CUtPAAAA CU3ALIL X OGA AMU%= 2501 ACUMMtI A TrIT1MPG 86 HIUMl~ 806 C3lUUAA CUUUXMC X CGA ALML4JAWC 2502 GTA~T T TI'IV= 87 HtM.MA 807 tLUM~ CUA X OMA ALAUAAUA 2503 'TAM=~ T TMOMN 88 HUflMA 808 C)UMULA CtMALIXA X CMA AAAIJLW 2504 ATATATr T MV3C 89 RUM 809 AC UO= CM-NlMAG X 03AA AAAA1JMM 2505 T~A'1Tr T AGCCr 90 Ht1GAMA 810 AACU C~rA= X CMA AAAAALfl 2506 AITT A AGrr 98 HU1'rzAAA 8fl. AAAAAACC CMMUGAG X a3A ALtrUC= 2507 AAOA~ T 03rIrIrr 102 MO~A 812 AAA CtX2 X 03A ALCAACU 2508 i'GT T TrrlC 103 HLCXTA 813 ~ A3A C~A7 X CCA AACCAICU 2509 ~AGIG=' T TrrC=I 104 FHtrATPA 814 AAG3MA CUML7MG X C3AA AACCAC 2510 GriGr T TICIT 105 KHxTAA 815 AA3ADfl3 CMt4IA X C3A AAA)CA 2511 MOO=IT T 'tCCC1'I 106 HtUfl4TA 816 CAAG3 CULIALGG X UMA AAAAAC 2512 TOG7rrr T CtCrm= 107 EVATA 817 tCAO ctGALtM X CCA AAAAAACC 2513 U;I71 11 C CC==I -12 HUMLIA 818 AAAAUIA C MAMG X CA ~AGOAA 2514 TrITtCT T IMT'rr 113 HCATArA 819 C.AAAADC CMtXWNG K A AZ303A 2515 rE'iCri T GATMrIG 117 11142TAA 820 AGtLXAA CLIAUM X CMA AUCAAG 2516 CtCrI7, T TII= 118 HIC.TA 821 AAGA1CA CMAUGAG X CGA AALXAAPL 2517 CITIlId T TIMICI 119 HMTPlkA 822 GAGU CMPOUG X OM AAALMAA 2518 TTIGI= T TGT 120 HL~rzATA 823 CAW-ir CIGAMP X CMA AAAADCAA 2519 I'T7A T CGI'I= 124 H14MM 824 aLXXXA LIX2LXAD K aMA AIXCAAAAA 2520 TrrrI= C TI033 126 H24MM 825 anGU CLtXWMX CK LA AGAUCAA 2521 TIC=~.' T C0MA 127 1HIMAMh 826 ACLUGl CX;UJMG X COA AGAUCA 2522 TTGA=~ C G03 r2 136 HUtzATA 827 GUr-A LGAnUiG K CMA ALCEG= 2523 G~a r T C'CI~CO 137 HtICAMAA 828 COMA OULIA G K OMA AACU=l 2524 C(ACAIT C aIUCCA 140 HUA 829 AUMEM CUGDML K CA A=~Ct 2525 CAorIMM, C CCC 149 Kt4MA 830 AACGAUA OUX K CA AtUfl3 2526 CCC A 'I']auI 151 HtMGAMA 831 ACAIJ CUGI K CCA AVL'G 2527 ACC T AIII 152 HLICAMA 832 AAAA3 CtnAGA X CA AAAWOC 2528 COCA=~ A 'ICrG r 154 Ht1MMA 833 GCAIACAAC CL13AUGA X CGA AM~A=~f 2529 CA'ffT C GIITI' 157 11'lAMA 834 AorcAc CfAIM K 0:;A AC~nkXJ 2530 ATI!G= T r r WO 00/61729 PCT/USOO/09721 75 Table HII. Hammerhead ribozymes targeting GATA transcription factors (1, 2. 3, 4, and 6) and the complementary sequences 160 RUWAMA 835 AOCXXX CUGLA X 03A ACAA=I 2531 ATCIGTI~ T GXCT3r 166 HLCd 836 GAAAA CU=, X OSA AC3CA 2532 G770=r C Grr=i 169 HUCNfAV A 837 GGAGLGA CUAUGAGi X 031A AJ3 2533 GCCG= T TrwCIcc 170 HUWATAA 838 GOAGG CUGAUG1G X C@ZA AAfCC.A 2534 CtUIt=I T WIC!tt 171 HUWA~kA 839 GGGGAGA CGAUGAG X OSA AAALC m 2535 0I 1 11! T CICrttt 172 HUW2UA 840 CO3AG C!UGIiLA X 03A AAAA= 2536 GCG=i~ C TICrt 174 HOWATAA 841 CO133 CUAx tx7 X C[IA AAAAAM 2537 CTr C 'TCC= 176 RUM.Th 842 cA03= C!GALEu X 03AA AGAAAA 2538 TITIC'= c CCCIG 188 HOWAThA 843 AGGLIMC C UX][X2AG X CGA AGC 2539 GCM=~ C CIIGC 2191 KUIC.A 844 COCA= aCLX;rA X 03A AGA 2540 'iGIwr T G.CCI= 231. HL]JAA 845 GUttt= CU3IAIXAG X CG@A 7ALflUt 2541 C33A C GL-433SC 245 HOWDk7 846 ~AGttI CUGA=x X CGIA AC~a 2542 CAC=~ A TCGA 247 HUW.kA 847 CAW= U CXAUGA X SA~A AU7CN= 2543 CCAMIR, C ALGTI= 254 HUW1%M 848 CCU= CUAUG7) X CGAA AGCU=t 2544 TCGAr T GC~CAE 293 HC3WATA 849 CtCX'Cn CUCAUGA X O:A AGGC= 2545 CT=lIC A CCG 317 HOtWJAMA 850 axU1GAr7 CIAU~g X O:A AG3 2546 CGGCt= T CATOAz 318 HbLrAMA 851 CmGJ= CDCAUGA X C:;A AAGL= 2547 GCtt' C A==~ 341 HUWA72A 852 C03GA CXU3oA X CGA ACC 2548 COCO c ciCG 344 HICWA 853 .ACCUM CrJM.LxAL X 0:;A AGM 2549 CnOiwr C GCCGICr 351 HtI2M .854 GODGA CUGVlAG~ X CaA ACTXn 2550 TCOC~ C 'IAICC 353 HUCfATA 855 U333=l CLGAX X CCA AGCt11 2551 GCCcA=t A CCICXX 377 HU4EAA 856 CAOA CUU2 X C3A AG0L= 2552 03~ro C CI~I'I 380 H[]WAZrA 8577 CCGA C70 X CGA A0D 2553 GIWI' C agiWIU 384 EUrA 858 A00 aUIVtZ X OCA AC33AC 2554 TCIt=I T CIOr 385 HUDCAA 859 CA0CCC CULCLI X CQIA AAOA 2555 CC~ICr C RAXAIG 395 HOW-A 860 GGG CUC49JGAG X 03A A. 2556 G3I0= C CPIt= 398 EtJUfAM 861 CLUENA CtXGLXPG X 0:]A AGC 2557 riCI r A CCCA 402 HIUAJhA 862 Ctf C 1ACA X 0:A AGL0 2558 TCCM C CO 422 1LUU 863 03AM CtGAU= X 0A AGC 2559 CO33 C '~t 428 , IJMMTA 864 G3C COAUGL X C1;A A03CAG 2560 CItCI=1 C C3A 440 HL14MM 865 tGOa aCtI0C X O:A A033 2561 ttOC r C G303C 467 HUJ3A 866 C0CC CU1GAUC2 K 03A A. 0 2562 GOC C TG11 535 HaIMM 867 0333 CGAUGtG X CGA AGO 2563 GAG r T AAC= 536 HLICA 868 G033 CUGAUX~ K=kA AAGCU 2564 AGII' A CAC 554 , MMMM 869 A-3 Ctr1ILXCL3 X 0:;A A. 2565 GCIGI' C GC3 563 EL14MM~ 870 03AG= CUGAIXW X 0:A AG3 2566 GC03r T C7CC'I 564 HtI3A 871 G3%G2 CUGAUCG X CA AAC 2567 CCU= C IWI'I= 566 HUC40M~ 872 C32k CUGAUG K CCA AGA 2568 GCGC= C CI'1t= 569 Fi1A 873 LLrCt= CU~g X CCA AGAGA 2569 CrICi= T CC0M 570 HUWAM 874 GLItt= CUZAUGAG X CCA AAGACA 2570 TICIWI C C033C 587 HUW~A 875 .. - CGA~tZ X C:P AC 2571 CAC~ C CCI= 635 H=40M 876 CACE=f LIAUi K CA AO= 2572 'TGC3 A CAGIG= 686 E1MMM 877 C33 aOICILA X CSA zACUO= 2573 CGG AC3 = 701 HLC0 878 AGX: CU20= X QPA AGO= 2574 CoaI' TC03 WO 00/61729 PCT/USOO/09721 76 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 702 HUMOMA 879 G cc CX2AMX2G X CCIA NXXX 2575 OC03=I c xCrrc 710 FMTAA 880 UOflIUG CtMAIX2 X MAA AGLCCXG 2576 C03= C CIAC=t 713 EUIrA5M 881 GOtflPG CUGiflG X 03AA AGA 2577 GOiCc A CICCP2CC 716 KMIA 882 AGXtX CUGAMAG X 03A AGJAG3PG 2578 CItCr= C ~CwrC 725 Har.AMA 883 AACm33 CI2At X CCA AG33= 2579 CALttr A cC03r 733 MrIA 884 GCAIJ3J CtrALxKL X OSA AGtC= 2580 -ACCCD= T A~a= 734 HtMA 885 C33CCALI CM491DAG X OSAA AADZ= 2581 CttCIT A CAT= 755 HCkT 886 03CCCAG~ CUAUGA X CXAA AOt= 2582 iGGG r C cmxa= 779 HUA 887 GOttXG CUGAMAG X CMA AGC 2583 CG~Cr= C 0t3CC 791 Ht1MAM~ 888 GU= CLMAMAG X M!A P03 2584 Cnx'Ccc T CGACAGM 792 HUATA 889 G33CLX C MUGA X MA AG333 2585 oGCCri C GACt 804 HUMMAA 890 CtLfIL OtXrAEXMG X CCA A0U 2586 AmrCC r C COAi AG 853 MrIA 891 CAAC CUMAGL X OMA AIULXXJ 2587 ACCCCAAT C T'IA. 855 HUDMA 892 MA =~~I CMfAUGXG X CGA AGLI= 2588 CCCAMCT C GAM=T 859 HU'LMAA 893 GUCAAACA C XAUGAG X cXMA AU03AGAU 2589 ACI= A IUITIGAC 863 HUZThA 894 AGXGC CUAWAG.O X CA AM' 2590 CATAur T TGAC~ 864 h7JMCAXTAA 895 AAG'= C GUAMA X CaA AACAUAU 2591 GAMGITr T CGAMI 8'72 FKICAMA 896 CxUUCGA CxGAMAG X CMA AGIO 2592 EGACI T CRMC 873 191MATAA 897 CCUttA Ct'3AIflG X OA AAGUMUC 2593 CAM=T C TaGA 875 HUDAMA 898 UGCCUULU O3LI"-XM X CA AGAG 2594 OAC='~ C AMN 894 HtELMAA 899 CCACjU CUGAUGA X COA ACCA 2595 CGr=I~ C AACI= 907 HUD~ATA 900 Gfl3M CUMJWflAL X CA PtCC = 2596 Gi~ A 7'I= 911 hIMPIM 901 GC333CCXLUXG X CCA ACUAO 2597 GOCMr C CACO 921 HMUM~ 902 C30ttCA CUGA=X~ K A AGO3J 2598 ACCOMr C 70A 943 FUD'MM. 903 CAAA CUAUA X OA ALCCO 2599 GGACr C ACA 947 HUMAMA 904 tGCA CaAUGA X CCA NIJ]CCC 2600 GOGIC A WCIGI= 949 RUMA 905 GM33C CaE-0GA X CGA AIJMGL'C 2601 GI1KM= C TIUICA 969 HUCfATAA 906 WUtnOIA CtXPLtMG X CXA AGCA 2602 '1UI= C 'ITACXk 971 HICMA 907 tutmfl2 acXL K 0:A AGG 2603 'iG3'c A coMA 990 HUSA 908 GCOXJ CGAxwMG X OA AUIfaLuX 2604 AA.T C AAO 1002 FIMAMA 909 03ayXW3 CtGAUGL X CMA A03 2605 C330 C ~ATC 1005 MUMMaA 910 L1JAGO= CUIGW X CGA AM= 2606 CCIZT C AAC 1012 111CA 911 CCGO CGAUGiG X CA AGOrXM 2607 'iANr C G3 1025 HaIMM 912 G32 LAM X OMA.AAC 2608 CtCi3r C 03It! 1031 R24MM 913 CU03 CLGUM X~ K PA AG03A 2609 GCCI C CtXX2 1047 HtW-A 914 GCa%~ CUGAVM x a3A A0C 2610 G3r C ITCM=I 1049 HUMA 915 U33ACA CUG X COA AGG 2611 G3Cic C CG7= 1131 HEMAA 916 UtCAUGU CIALUG X C:A AGC 2612 TGi3Cr C TAAP 1133 Ht1M.A 917 OCUCIfl CLP'Z X CIA G 2613 COC A CAGAG 1143 HtIAMA 918 ACCCO LIflAUMG K CMA AGCtUZl 2614 AMU=~ C CA3 1162 HUCA 919 CAULIGM CLAMPG~ X CA AtU33 2615 CCAGr C TIUAM~ 1164 HtUTAM 920 COUtJX CLMM K OMA AGAGO 2616 AG3C=t T GCA 1 185 HUCWAA 921 amxxn CUAUGAG X CA ALCX 2617 G%33A C akAC2 1219 Fucmm 922 axwtAnu arfAmul- x co AwqEcm 2618 ACIAAT A AA=t1AG WO 00/61729 PCT/USOO/09721 77 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1-223 HUMA 923 GLXU) C X-IYJAG X CGAA AUMMX 2619 Gt7TAAAT C TAGPA 1225 HtI-J'%A 924 tU J CXGAIXG X CSA AGJUUtIJ 2620 ATAAAW~r A AGCAC 1240 HtUlA 925 OCL73AG CU3AtX= X C:PA AGtCtL= 2621 CACA~ C Cr7CMC 1243 HUMATA 926 ALM=CU Q)AUGA X CGAA AGA 2622 AC~ICTr T CAGGr 1244 Htbr.AAA 927 CACnU CtY3AflG X CMA AADDG J 2623 AGCItC=r C AMC= 1260 HUCf~A 928 CGG=J CM1AMflG X COAA AGtrtr 2624 GGA= T CtCI= 1261 HtJAA 929 GC = CIXAMA X CCMA AAGOEt 2625 AGAGcr C CICtC= 1264 HtMA 930 OCfL'3 CUGAUG X QMA AGAA 2626 GC~Ir C COC= 1279 EtMA 931 CGJtXtX2 CMU3AlG X OGAA PDT 2627 Gcwrwr T CAGA 1280 HtIMfATA 932 AG1Utfl CUtXLDW X MAA AIG 2628 CiGT r C C~Ar-AA' 1289 HtIMA 933 ctstxfl acU3jjr,3 X CGAA ALGJtXfl 2629 CACrAC C CACA 1327 HUIA 934 CUxnrtxr; C~-A~rtA X CMA ~AC 2630 AGA~T=r C CCMA 1332 HU A 935 LIC JtJ CMUAG~ X 0CAA AL3M 2631 CflttCXI' C AC.3= 1352 HUC-IA 936 AGMCAAU CUGAUXTG X CMA AAG= 2632 'iGICr C ATCI=c 1355 HUM~fAMA 937 CGUAGA CMXAIX3G X CMA AU-A 2633 CtIG=~a C TCAC= 1357 HUM3MA 938 CtJG J CUGAUGA X OA AGU2- 2634 TG7A~rr C AM=~ 1361 HUMATA 939 tGLnx= aXDg X CMA AG G .2635 ATI=IE A 033 1376 HUMAIAA 940 CGiC1C CfarwmG X C3A AGECLG 2636 CACA C CMIGIt 1382 HLr.ATA 941 AGrtn CMfl9A x a7A ACC3g 2637 CICtC=1 C COCA= 1391 KICATA 942 MACtUA CUAUGAG X 03A Attfl3 2638 CCAGAr T CICiA . 1392 HIAA 943 Oaf!'LXi= ax2XMGI7 X OMA ACG 2639 C~ACAmT C TCG7A 1394 HIUMMM 944 uc~u= Ctaxmo X CM A43AA=~ 2640 cGrIG r C AGIK2G 1398 HMMA 945 AILM= axLI X CGA ACSAP 2641 TICI=G C AGrG 1409 R1JMUM 946 CALUOCC CLXUGAXG X CA AAL70 2642 I= = c MOO 1424 HEIUAA 947 GGUGlAIX CGAUGwG x aA AG0 2643 ~iwC~ c cATCCc 1428 HUMGATA 948 PACGf CM40MG X CXIA MGM=~ 2644 OtCI= C ~CtCCt 1437 HUCATUA 949 GCCGA CtM.LA X OMA ACAD333 2645 CALWT- C CI7= 1440 HLMAA 950 AG33 C axwxG X 03A AGAA 2646 CiCiwr C TCO 1442 Nt1'VAUA 951 uco axwoA X CMA A~GA 2647 IIC=t C GOCt'I~ 1455 HU43ATA 952 U~~n axUIXMs3 X CGA AGUU 2648 C7GAAr C 'ICakC 145-7 HIMcAmA 953 axrnm anaum x OMA AG;G 2649 GAAGIt C CCZM 1469 RUClA 954 GAAG CIAUGAG~ x a!A 1AEtC 2650 ACAGC A 'IT'IC= 1475 HMMONA 955 UG030 ax2UXA X CA APiCAUAG 2651 C7A i C 'TCCI= 1477 HL4ATA 956 GaAC C!LX2CX x A MAO= 2652 AL1GIOI C CO:I 1482 BECA 957 @LCU axP~rmG X 03A A0GA 26593 WICtC C AMC 1490 HtC4UM 958 LtCUOLG COAUGAG K OA AMtX3f 2654 -CGC C 'TCC@kC 1492 HIMMA 959 Go~rnn arAE)M X COA AGC 2655 GLImr C CAAGC 1505 HUEATA 960 ct XL Xf Camu K aM AGflU= 2656 GACA C CAGA 1517 MtIflA 961 UGJtMA CUGAUGA X CGA PLGLt= 2657 GMGGCI' c TraM~a 1519 HtIAA 962 AM=Jt CLIMXML X O:A AMAG= 2658 AM? T aAA 1528 Ht1'fAMA 963 CAGA axPLIGA X CA AMtfLXL= 2659 GOA= C TOM=~t 1533 HIJ3.MA 964 X =A anunAG x om ALazLu 2660 AGIC-ItIT C TIODi 1535 Iu~rAMA. 965 =27-xc CUAUC X OGA AGCL 2661 7CIGIc T GOOA 1546 MKMMA 966 GuC cuXqmG x oC;A AC==KX 2662 CtCiNT C AC=A WO 00/61729 PCT/USOO/09721 78 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1557 ixaA 96 C-Gr-%UCrA X Cr-A ALM=~C 2663 GOGA A ALC= 1560 HUU'ATA I 968 tACOCAG CtxiT.PGb~ X COA AtUY= 2664 GACTAAT C ACtG A 1568 HUrkAA 969 3SAAAU aiULA= X CPA ACtrC&J3 2665 CI= A A~T'I'tt 1571 HUMn.AMA 970 AGAG3liAA CArJCI3c X OSAA AtXA= 2666 - GOrAAT c rca= 1573 HUMAT?. 971 GAAXXA CGXAUGA X 03A AGALRMM 2667 CM~AXIM, T CItTIC 1574 Ht1'fAM 972 GSAAGAGG CMlALG X CCMA A Dt= 2668 GTAAaCr C CCTCC 1578 HLICZA 973 OGGSP CUCALUAG X 03A A3PG 2669 TcrIlw C ITtII= 1580 HUblA 9*74 CAGA CUMI X (IMA AGA03A 2670 'T'tICr= T CCCIC 1581 HLICAMA 975 MAMA Ct4XL3 X C@A AG=i 2671 'tctrr C CItrI= 1585 HtX' 976 AAUUfLr-A CUflDGAG X 03AA AG3A 2672 W'Ttt'I' C CIr.AATr 1588 HIbMAM 977 ?AlMxJU aXnw7G x aAA AOG~ 2673 TCC= C AAATICI 1593 1iUMATA 978 CGLIOAG CEJXt. X CSAA AIJUE3 2674 CCTCAAAT T CI= 1594 HtIMA 979 CtLOCA CtXGAGA X OSA AAULXJCAL3- 2675 CICAAAT C CI-A 1613 HMATAA 980 tULtt't C LUXP X CtMA AGLIt 2676 =IGcr T MAM 1621 HCX--.A 981 UtUMXX CQY-ALDP X CMA AMCtCCA 2677 TGGGGT A GAAA 1644 RMUM1~ 982 OCCC= CUGAUMG X CMA AGCA 2678 ccIGrt C CAG= 1659 lxkrA 983 ?AGAA C UX3A X CMA AGC 2679 GCxx3= C ciIICr= 1662 MUMMATA 984 .ACMC=X CPD3 X CMA A~AU 2680 G3CCr C 'iOC7r 1671 HUClA 985 GSAIJA CMAlGAG X CGA AC7= 2681 TGIC= A ATGACI 1678 HL4rJXTA 986 UtLX;UJ CtflJUJJG X CSAA AGCLJ A 2682 TAITGCr C MMCM 1703 HZCPA 987 tCtAUt72 MrflIA X MIA PJJrJ 2683 AAM= T GAMX 1709 HtLTA 988 ~AAUmr CGAUGA X CA~A AOJUCAA 2684 crI'iVG C GAA 1716 HtUMA A 989 CCUAACC CrUIPL X CA AUGUOM 2685 CGAAT C 7t0I'IM 1721 RUMAM~ 990 axuttt' ai~u7GAG am ~A m1 - 2686 AAWIC= T PA3kP 1722 HUGATAA 991 GCUUttCGAUMG X 03A ACCflA 2687 AICI'rT A G33SAA 1737 HUGATA 992 GAAAILC CUMUN X OA ACC 2688 Ga~iur T GOTII 1742 HtnA 993 ULrAGAA L7CUCIG X C3A ADtCAM 2689

T

i= T TICIAG 1743 HUMi 994 ALtU3SLA CGIGtX~ K PA, AACtA 2690 GI'IGAT T rTCICGA 1744 MrLEA 995 CA1nGA LIIA X CGA AAAICA 2691 TICT= T CICGAtG 1745 HMUM~ 996 GALMMt CUMUMPG X OMA AAAL= 2692 'TGGMr3T C TCGA 1747 HMMA 997 A03tU CE)GUGAG X CMA PaAAA 2693 CGTIt C Aa= 1756 H24MMT 998 AGCGUG CULP X CA .AG1EU 2694 AGAI' T TAA 1757 Ht2lA 999 CAGO= CUGAXLA X C1A AAGOL7. 2695 GAIGCI T ACC 1758 MMAOMA 1000 trICAGC CUADCu X 03A AAG fl 2696 A'Ir1'I A CAO 1790 Ht1,ATM 1001 tXXGLZU03 CLGU3X;3 X 0A A033= 2697 CtCC 'r T CACA( 1791 HZMM 1002 CKUX CG~tX2 X 03 AAG3GUGGl 2698 CLAIT C AGACA 1810 1UMUM~ 1003 AC0AACAU ~ x~ K MA AVOC= 2699 CACI=T C TICCIU 1812 9HrAA 1004 LiAM CLXUCW X COA AGAUG= 2700 CIKacr C 7CIIT 1814 F1143ATA 1005 ACLICC CUAUGA X CA AGGM 2701 GMIT C CI1I 1823 HU4L17A 1006 AALEX= CUADMG K CA 'AUMCA 2702 CIMIG~ T GGAGA= 1831 HLICAMA 1007 UOOAAG CIAUCPG X OM ACL= 2'703 TGOAG' T CII= 1832 HUM~ATAA 1008 LX)3A CLGJA K CIA APCL= 2704 GGAGCT C TMKXA 1834 Ht1rTAA 1009 tflutxA cumumG K cxA AcAtU 2705 WTAGACt T Mr=VA 1835 HICATAA 1010 xxv= mm= x aK iA AAAA 2706 CEIC=I T CtVT WO 00/61729 PCTIUSOO/09721 79 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2. 3, 4, and 6) and the complementary sequences 1836 I1ATA 101.1 CAM=ufl CMXAIX.AP X CCA AAAAC 2707 A~CT=tr C ccA 1346 HFUAMA 1012 (3GCAAG CflLX3AG. X CMA ACALUtJ3 2708 CAAGPr C riuTcc 1849 11MATA 1013 CA33A CUGAMA X CakA AGCAi 2709 GATG=t~ T GI 1852 ETIMAM 1014 ?tflC= CflAUGG X CMA ACAGA 2710 Garwrt r c ccwi= 1861 HFI-A 101.5 CAUO3 CLr.3JAG X OSA ACCG 2711 CttI= T CCCCA=I 1862 HIC~AM 1016 ACAGXM3 CUMAG X OM AACL= 272.2 ctirr C C~CCA r 1876 HUtzATA 1017 Cr-ACr=z CMtWAG X QMA AGCCC 2713 TGIC A G1ACO= 1887 HLICIATA 1018 CAAXXA CMfAMAG X CCAA ACtCA= 2714 -Ct'GI T TIa=TI 1888 HtMAMN 101.9 ACAUGM CMnUir X CGA AALtAM 2715 CG ~i r T TdGr 1889 HAUIMA 1020 CACAAUGn CflAD=~ X 03A AAACtCAC 2716 G703=T T I'%IG 1894 IUUflATAA 1021 AGAAACAC CUMAM-AG X 03A AUX2AAA 2717 TITtt=A T MI='~ 1899 1RUMAA 1022 CX2IEPCA CMAMPG X CC;A ACACAAUfl 2718 CAIII T TIC 1900 HCTA 1023 GOLaPC W3AG X CMA AAAAU 2719 ATIGI=~ T C~G 1901 HIcaTAA 1024 OCXIUA CX3AUMGP X 03A AAACCA 2720 TIM=~I C TAC 1903 HUD'fAM 1025 UE3 CMMJ=X~ X QGAA AA 2721 aiGriwr A GLCACO 1916 HUMMTA 1026 UGUUCUCA CUAU X CMA I4C= 2722 CGAGA C TUAA 1955 HUOAMA 1027 U003= CUGALUAG X OMA AOA 2723 ccOC=' C CAC= 1974 HICNfAMA 1028 GOCAAA CtXAIX2 X CMA AOCCGU 2724 GAVX S' C IUITI= 1978 HUrACM 1029 AM C MtJAG X OaA ALAI= 2725 GA=IGur T TCCP 1979 HtLflATAA 1030 tAAUO CtrAIGAG X CGA AACAGAU 2726 CATC=r T GCA 1987 HMATA 1031 CA~rG CMALUIG X CGA ACU3C 2727 MCC A CCIM 2021 HUMCIA 1032 GA30 COGAMA X COA A033= 2728 ~ CAGO T GtCOCA 2029 HIMMTA 1033 AG03= CUM)M X OCA A3= 2729 M'1CICT C CAM= 2033 HLI.CAM 1034 CUCAGM CUGAUGAG X CMA AIXXW= 2730 CCA7=~. C COrITW 2038 HUMMA 1035 Cnxt'O r CUSAMAG X CCA AGOOGAU 2731 CATCr T GA3 2061 RUOAMA 1036 G=IXMM CuLIGA X 03P AU 2732 CCtIG. C C~kM 2065 HUIlA 1037 UUOGUIAI MrIMAtf X OMA AGGI 2733 GCT A AMCCAA 2068 KM TAA 1038 AGAUtUO C!LU1MM X OMA ALM~ 2734 'iCCtI~AA A CCAAWI' 2075 924M 1039 uomcm ctam x OmA AU~XMR 2735 MCa;AA C 'IGLI= 2081 Mr-AM 1040 CAGUt= CLGAM X C3A AGCfl 2736 ATWIGcr C CAAAACTG 2120 HMA 1041 UCCO= axMUNG X 03A PLMC 2737 TGACTr T CCO3G 2121 HICTiAA 1042 CEXXXA CLGAM X CCA AAGUE=f 2738 GWicIT C C03 2132 HLIA 1043 tU300 MGM=~ X CM AGU 2739 GOCIA A GO 2143 HICATA 1044 GL13GL MUM=X~1 X C:A AG 21M 740 G303= T AACA 2144 HUATA 1045 UGGU= CAL70A X C1A AJAU= 2741 GOOMr A ACC~ 2164 HMPM~ 1046 AutnriAn CMtfl3,g X COA AGO 2742 COA C AICAAAU 2167 HI1OfAM 1047 UOCUnr CanVA X C3A AMA=U 2743 A ICrCT C AAAA=I 2186 HI{NA 1048 UGOOA CtLr4VXP X CMA AGU 2744 7G1MAL T CCLIO~ 2187 FUCAM 1049 am cutvim x osA APGaxf 2745 GOCACIT C 'IOCCA 2189 HtJCAMA 1050 Acaxm- mrmxnI am ~A mA 2746 cwncr C CCC~r 2202 HEICNAM7 1051 GG= CGAGA X COA AGC U 2747 AGI= T Ctt'It 2203 EMMA~IA 1052 AGAG3 CMLIA X CA AGO= 2748 GG~TG C CtwiC r 21 HSGAT6PR 1053 G(tUo arfAmAG K OA MO[ 2749 G3:7= T C3CA 22 HSGM6PR 1054 = =r~ C~iaLD g x 0:A AA 2750 CALt' C G303 WO 00/61729 PCTUSOOIO9721 80 Table III. Hammnerhead ribozymes targeting- GATA transcription factors (L, 2, 3, 4, and 6) and the complementary sequences 35 HSCTA6PR 1055 C UANA CM1AXAG X CMA ACG 2751 AGiG= T 7GrrAG 36 HSGTA6PR 1056 CCCWAC CtMAD3A X CMA AACA= 2752 GCIOIT T GT 39 HSC4TA6PR 1057 GALGttU CMAWAG~ X CA ACAAACG 2753 CIVITI= T TGIC 40 HSG=A6PR 1058 CSttU CUGL)-A X CZAA AAA 2754 EGrI'fr T A00 41 HS@.T6PR 1059 C03AtCMUA X K %A AAACAAAC 2755 aITMI'1r A GaxrI= 47 K9WAA6PR 1060 GACU=~ CMAMAGb X C17A AGCttUAA 2756 TAD r C G3IGA= 55 ISATA6PR 1061 CCU,-4U CUGJGAG X OaA ACLA= 2757 CO~GGAT C CATA 60 HSGTA6PR 1062 G3uCc CMAlGDG K CMA AUIOGACU 2758 AG7CCAT C AGA 79 HS=6PR 1063 L13COGA CtUiLUAG K CA ACt 2759 GCIOCPor T TICC03 80 HS~TAGPR 1064 CIXX) otCAMrG X CA AACEGCA 2760 CI'AGIT T iTCC 81 H93AA6PR 1065 tU3 CUALA X CS AAACti 2761 70CAIT T CCGO0A 82 HSGALIA6PR 1066 CUCx= CUMMA3P K CGMA AAAAC=f 2762 GCrivr C COCAA 95 HSGAaTA6PR 1067 GCOCJ CLX i. X COA AZCfl3 2763 AGA A A~G 106 HS3AT6PR 1068 034A CrUX2; X CGA A00 2764 AG3Cr C CICIC=t 109 HSYCA6PR 1069 AAGGAGA CxtxLK X GA AGA= 2765 cocicr c m-=rrr 11 HSGA6PR 1070 AAAAAA CU7Lr3xZ K C1A AGAGGAM 2766 CC0IC C ICCrI'r 113 RSGTA5PR 1071 AIL.AAAG CUXAA X 0A AGAG .2767 TCICIC C CrrIT 116 HSA6PR 1072 tMWA.AA CUGAMXG K 0AA AGNGG 2768 WCIWI T Trnk=~ 117 HSGTA5PR 1073 GUGAAIJAA Ct,-XMGJ K CMA AAG2GA 2769 CICIC=r T TnIU C 118 HM6PR 1074 GgflAALWk CL13UXG K a3A AAG 2*770 TC'IWI- T 'IATIACC 119 H9GTA6PR 1075 tOGLIGW CUIMI K CMA AAAGGA 2771 =3717rI T ATIC 120 HSGA6PR 1076 CLI3LGA Ct'GLUA K CMA AAAAPC 2772 'TCCIrrI A TICM 322 HSATAPR 1077 Utmfl CLGUM X~ K A AUAAAAG 2773 CI'rIT= T CACM 323 HSCAM6PR 1078 C~ LO= CLEXPLXW3 K C~A AALUAAAA 2774 ITITTr C ACA 152 H.GATA6PR 1079 GLM CULO K COA AGC 2775 CC03= C GOM= 158 HSGTA6PR 1080 CAGO= UP A K OAA A03CM 2776 CICt3T C GCCOU 174 HGA6PR 1081 @GAGC CGAtX2G X aA .PGOC 2777 GGOO C GCrii 179 HSGA7.6PR 1082 G0GM CTJ~IXG K a3A AGO 2778 CCI= T CICIt= 180 BSMA6PR 1083 MO C UtXP43 X C3A AACM 2779 CC33Crr C 'ICIC= 182 RH.TA6PR 1084 .. O CEXUIIW K CMA AGA 2780 CGOCt' C 'TC00C 184 N.9G71.EPR 1085 C00MCUEPLA K C3A AGLP)A 2781 GrICI1 r C 203 HSGAMSPR 1086 CLICAUGG K CODA AGOG( 2782 AM =t~ C 216 HSG.AAPR 1087 GCALIG CUXXPL X CMA AC3C 7783 G03 T CIA 217 , S-7G.6PR 1088 0I3CA= CIXU2 K COA APO 2784 ctGI'I C 'Ta:; 219 FSGTA6PR 1089 L1303CA CULXPl= K OA NAGACO 2785 GriM r C CUG 246 ESSA.6PR 1090 CUA = CIAMMn K 03A AGD!C!r 2786 GAGG A CAMA 252 R9STh6PR 1091 IrX2QA= CfLrAUM K CGA AOMtUA 2787 CLrGA= C AGriC 257 HSGAT6PR 1092 GC0tt LGAIXMG X MA ACCIA 2788 CUM= T GB 285 HSGAM6PR 1093 CGX~( CUALM K CA AGOCAU 2789 GAGCI T CAIM 306 HSrAn6PR 1094 a== CLuxLr K a2A AWiL 2790 CIMI=T T GX A 318 H.MAMMP 1095 C3C CLxxpUtG K OA AGOO= 2791 GAGC~ T 033 319 HSAE6PR 1096 ~ t CL AUGn X C3A AAGC= 2792 Tr~'1 C 033C 348 Rsamm6P 1097 Atrrn am m. K aA Aax. 2793 -c~w c acw= 357 RG6PR 1098 GCCO cuMti X CC 'trtxOC 2794 a;Ct' T 'IUG= WO 00/61729 PCTUSOO/09721 81 Table MI. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3. 4, and 6) and the complementary sequences 358 HSGATA6PR 1099 -CCO CMXAIWL3 X C:1A AA=CUtt 2795 PCAG r T CCG= 359 HSCATA6PR 1100 CCtfl CarJ.G X 07-AA AAA3Gt)C 2796 CI'IT C CACG 375 RS@.TA6PR 1101 GO flfl CMUM X (SAA AM==X 2797 =M=tt C CAOC 386 HSCA.TA6PR 1102 GAff3= COAP X COA A0X3C 2798 'COCC T CCtC'a 387 KSGTA6PR 1103 AGAU CtflAIGA X OSA.AO 2799 GCIT= C CtJC r 394 RSGATA6PR 1104 cmaGA3 CtAIJrC x a2A ALU33WA 2800 mrct= c ItTrt' 396 HRATA6PR 1105 ACAGA CUlAtX X 0:;A AGOG=~ 2801 CxCttCi= C T ICLW~ i: 398 HSGATA6PR 1106 GGACGM CMfAUA X (JMA PAA 2802 CCAICI= T CCltIC 399 HSGATA6PR 1107 ~AGAL3 CtLrALXW X CSAA AAAA 2803 CATI=M C cCItGIm 402 HSG.A6PR 1108 AGAGA CMflWD X CMA AGAAA 2804 CTCtT C GIWIWI 405 HSGATA6PR 1.109 AGAM3 CMXW= X 03A APOAGSA 2805 IIWITI C a'icCr 408 H.SUAIM~PR 1110 AOAG CX3AtXW X 03AA AGAC 2806 CI103 r C CIWIC T 411 HSGAM6PR 1111 AGMZG CVLAIXP X CCAA AGAGA 2807 GWCtT C CTGIC 417 HS-..T6PR 111 Cmt= C)AI2 X CMA AGAG 2808 CItCIC I C C3 467 HSGA~k6PR 1113 = CLIGAU X OMA AGC 2809 WA r C A1W C 472 HSGTA6PR 1114 tCCGUG CfLrAIM X CrIAA AIGAtPGf 2810 ctIcA~r c aok 507 HSG~r6PR 1115 GCGCG CfLrAX= X CMA AGO33C 2811 GOrC C GCIGI= 517 HS=I6PR 1116 UAGGACU CMXAL= X COAA AGA 2812 CIGitr C AGrICM 521 HSGTA6PR 117 AGCUAO afLAIV-l X MA ACMAGM 2813 iTiCcr T CC:P 522 HGM(PR 1118 AACU cutAIm x a2A AALY.AD 2814 GiCarr C CTAC=T 525 HSGAAPR 1119 GCAA CIGA X OM GAC 2815 CArt' A CI't= 530 H9GTA6PR 1120 GOGM= =293=~ X 03A AGOUG 2816 C=XI' T C3Ct= 531 HSGA6PR 1121 ~Aif CUGAUGAG X COA AGCLIA 2817 aiM0rr C GC.~aC 536 HS.Ak6PR 1122 ~ a Ct =20MU~XG X Cx;A AMAM 2 2818 CIT C CtI= 540 HSGATA6PR 1123 CUGAUGAxG X 03A AEG 2819 CT T 03033 541 H.SrAk6PR 1124 GMBLC CUM)=~ X OMA AGGGAM 2820 CATwr C G333C 548 NSGATA6PR 1125 tUflO3 L17GL x aM OC 2821 T033= C CCA0& 560 HSG.Ak6PR 1126 A003 LtGAUN X 03A AG3I J 2822 AM =' T COtT 561 HGA6PR 1127 CAG3CCtM.tXP X CMA AGO= 2823 C3IT C G33 574 HSOATh6P M18 0330 CUGAUGL X CA AMCt 2824 CCIG= C G3 597 H93AMA6PR 1129 CaxAG= CUMXwx X OGA ACAGO 2825 @.P~iO= C GAMU 612 FSGA6PR 1130 ACOCA CUM=X X CMA AGC 2826 G~GGCr T G~G 621 HSA~6P 113 -GOLA= cu2mDmL x aA A.GCQ 2827 G~UM= T CACI5 622 HSGAM6PR 112 PDLU CUGAI3AG x aA A3CG 2828 CIrIM= C AMiWrc 631 HSC.A6PR 1133 GoUEmr CUMVMG~ X OA A3UAU 2829 ACIM1' C G~MA 666 HG~6PR 1134 CG03l CL2ICAL X CGA ACACG 2830 GCIUI=1 C CAC 693 HSGAT~fPR 1135 C33 CUGIflPL X CGN A03 2831 GAO T COA 694 H&A6PR 1136 uoo actx &. x K AGO 2832 AGCIT C GCCCA 720 HSGATA6PR 1137 GOOD= CtGAUGL X CIA ACU 2833 G3GA A CCGA 730 HSAT6PR 1138 AGG= CUAUA xXIP aP AGl3GC 2834 C CI' C GC3 737 HSGA~k6PR 1139 OfL33ALk CLIGAMA X CGA A00 i.3 2835 'TC37r C It~ 739 HSGAA6PR 1140 mtwlA c 7vLw x a7A A 2836 GC03T C 7CA 741 HG.I6PR 1141 Ct1U fl IAtX;;G X OMA AGG 2837 OOItI C CAOCG 752 1HSMaLkSP 1142 G03 aXU.IxML X OA A~CtHE 2838 GCAO C WO 00/61729 PCT/USOO/09721 82 Table Ill. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 762 RMAT7- -R 1143 CGCC=t CuX~JGmL X C:IA A= =l.~ 2839 GCDC=~ A mc= 783 HSG3AA6PR 1144 AM=2~C Ct)3A X CMA ?LGttC' 2840 C300a=r T CUM=r 784 1-TGATA6PR 1145 GAG-I C~wJA X GMA AGC3C 2841 G33ITr C G7C 792 HS93ATA6PR 1146 -033CGC CM~AEXA3 X CMA AGG 2842 CXIO2IM= C ICOl 831 HSGATA6PR 1-147 JAACO CflAMAG x aA AGCU= 2843 GOCCA~r C CCit'r 838 HSGA~Ik6PR 1148 GOCACGA CtflAtfl x a2A AGW 2844 rcCCCC C IACG 840 HS9ATA6PR 1149 tflGCAC CflAMPG X CGNA AGC 2845 CCCOt' A QIrGCCA, 863 HSGATA6PR 1150 CACAG CMUMLG X CMA AMtCMi 2846 CGIT T CC~AT 864 HSG~Ak6PR 1151 GCAG=f CMfAtMA3 X CGA ACCtAC 2847 CGicxrr C CATG=I 880 HSGATA6PR 1152 WGUA= CLT3MLG X GMA AGDt 2848 CC03= A =AC 885 ,H.92A6PR 1153 GCfl CMXA= X CXPA ACOP 2849 CLEAC= A CCCI= 900 1R.TA6PR 1154 LCLID CUGXALA X OMA ACtt= 2850 GAG T C CGC 956 HGE6PR 1155 MAO= CMUXMG~ X CMA A00CCI 2851 GCrG=c C N3Lflrr 963 G~ATA6PR 1156 UflX= aflALU X CGAA A3CEIG 2852 wMAOMr C G3C 977 HSCAIA6PR 1157 GCOOA fLrALXM X CIP A033= 2853 AM =t' C c;M= 981 H9GAa6PR 115C8 COmL)3 CMVlX2G X OA MOM 2854 cct'r A CAG 1038 RH.MMA6PR 1159 cOOU CMflMtG X CkA AGCP 2855 COL'r C AGC 1054 HR~ATA6jPR 1160 C03 CUC4)3AG X COA AjS 2856 GCOCA=I C IGOX 1056 HSGA6AIPR 1161 AG3 cAI= K CMA AG~a 2857 GCAIt C G303 1065 HSGAM7~6PR 1162 AGUA= CLMAlfl K CIA AO 2858 G3r3 T 'MC= 1066 HSGAIA6PR 1163 GkUG CUADA X CA A-D3 2859 GCGrr C CtOICi 1071 RSGA6PR 1164 t13MM C2M.P K OMA AC3A 2860 crIttw A CIIM 1074 H.GA6PR 1.165 GCU= CtlLOGA X CA ALGA 2861 ctt'CrI7 C 'iTOCCO 1076 HSGA~~A6PR 1166 C333= CUGAUGA K CMA AGGM 2862 CrCT C CG 11.20 HGaAPR 1167 GCOGj CLXMG~ X CGA AC-7 2863 MUP T 'TACO 1121 H.SGAPR 1.168 COCO= CfLGAG K CA ACL' 2864 C33Gr T.AOO 1122 HRTA6PR 1169 CO= CMfAMAG X COA AAC= 2865 G3GAGrr A 033 1-172 HS9kTh5PR 1170 MOM CtLIM K CMA AC003 2866 ~G T A GCI 1206 HGM6PR 1171 Gm3= CUAU X COA ACU3l 2867 GCC A CAC 1212 HGM6PR 1172 CCzCG axIGAUGG K CA ACCLVJC 2868 MUM=r C GCG 1218 HSOTA6PR 3.173 CL13AUM X COPA ACGOM 2869 C03=r C 1245 , 3gML6PR 11.74 G3mx= CUAUGA X COPA A04U= 2870 co Tm A CCALTAC2 1277 RgGAMA5PR 1175 G33 CUAUGA K a:2A A10I3=~ 2871 ACACT C CGG 1287 Hg~kMM 1176 A030 CLItxw X O:A A033 2872 akGO A CICOr 1290 HSGATA6PR 1177 03P aLIGA= x aA AGUIPM 2873 CCWTC r C G WCC 1296 HSGAMF6PR 1178 CCOAM CGAUMG X CMA AG30A 2874 ai7tO r A CG70 1338 , SMT6PR 1179 GOCX 3 CUGALA K CMA AG0C 2875 C30AT T OSAC4= 1339 HG.TAPR 1180 G33rt LTJGAIx X CMA AAGOE 2876 GGACttr C GAGA 1387 H.AM6PR 1181 GCT= CIL'GUA X C1A AGO 2877 GCC C CCC; 1403 HS~6PR .182 = =n CM40A X OMA A. O3 2878 CC03= C CAGTG 1431 HSrAM6PR 1183 GOrU= CLxIMUGA X CCA ACGfl 2879 GAmIur C CCflG= 1461 HSA.6PR 1184 WMALIG CLyIGAXM K 03A AG~tM 2880 CIGOT C CAMCAGA 1465 RWMAi6PR 1.185 axrn caxUGA X CCA ALUGA3O 2881 GOIt= C CAA 1503 j .TA6PR 1186 TME =D CMfAMMG K CMA 2882 ~C0 A C~II WO 00/61729 PCTUSOO/09721 83 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 11525 HSwA6PR 1187 Llt)r= CflNJO3 X CM~A AGCCCOA 2883 T03= C TAAX1 1527 HSAZA6PR 1188 UCUUt CUGW3AG X = ACA CC 2884 C333= A cAA 1546 HSGATA6PR 1189 Mom CflAEXW X C13A .Awmxi 2885 ACT C AG~CO 1558 HSGATA6PR 1190 GOUflAI CUMAG~ X CMA A033=t 2886 cxxxtt' C ATICAGt 1561 HSGATA6PR 1191 DC33U CMAUMG X O:PA AGAG33 2887 Cttt = C AAC 1583 HSGAT1A6PR 1192 CCOMlIfl CMUKfl X 03AA AGCA 2888 GO== T CATA3 1584 HSGATA6PR 1193 GCOGU CtflALGA X CGAA AAGO=C 2889 C'r1CI C AC= 1587 H~SG PR 1194 OCOO CtflMDG X CGA ALM=a 2890 GC~ra=. C AC 1597 HSGTA6PR 1195 GA C CUGAWNIZ X CMA AOCtG 2891 0030r T GAT=t 1602 HSA6PR 1196 C~AC C JUAMA X CGA At=A1 2892 GrIf T MCC=GI 1605 HSGTA6PR 1197 UXXXACAG CUGIA.L3 X (X:YA AAUtk 2893 ~TIA C CIt~t= 1619 H.ZAMPR 1198 LUmn= WMXJGAG X CMA A=XM 2894 C~CAA r C ACCCC 1631 HGAT6PR 1199 UAAG=l CMAL I) X 03A AGmJX 2895 CC.CACr A CCC 1638 R9GATA6PR 1200 tUO = CMfA[LA& X a2A AGLOfJGM 2896 TA~kDCAr T A~X 1639 H9dC.6PR 1201 CtX CMAMAIr X COA AflG J 2897 ACCACCr A 'ioxGCA 1679 H.OA~PR 1202 GAELA CtMALX X COA AGAL 2898 CAZIA T GI1GA=I 1687 HSGATA6PR 1203 UtAUG CEr.AEIYG X CCA AGCCC 2899 ~I70A= C =TA 1689 HSGATA6PR 1204 GUtMAtX CUAMA X C13A AGGV 2900 mccicr A CAGN 1699 HSGATA6PR 1205 ?LCCCAM CUAU= X COA AGLtXD 2901 ATIAAACr C C~ZIG P 1720 HSG.AMSPR 1206 UtrXtMW CLIAM x aA AGmxG= 2902 AMC=' T G: 1724 HSGTA6PR 120 UUEXXXtDM CUXM X CCAA AGCAA 2903 ~CAr=~ A TGAAAAA 1741 HSGT6PR 1208 a.103= CUGALUs3 X COA AnttC r 2904 GAMT T C.AACCG 1742 HCAT R 1209 CCmxG= UALXMGx X C3AA AAtUt 2905 AGATr C AACLA 1763 H0AT6PR 1210 tUIfUG CUGAUMGC X CMA ANSfL1J 2906 GAAA A AGAAP 1771 HGTAPR 1211 GA1UtUE C.1X~z X 03AA .AIflXLUU 2907 AAGACA A AAA=~ 1775 HGA6PR 1212 CtUtXIGAtJ CUGAUGAG X COA ALMA=Ifl 2908 ACMA A AAdCAMG 1779 HSGAM6PR 1213 AGU=l CULIM X COAA ALXrXLW 2909 AAATA~AA C AAAGCIT 1787 HSM6PR 1214 ACAA CLIUMI X COA AGJCIIW 2910 CAAG~ T GICI= 1791 HSGAm6PR 1215 UAULMC CUflAUGAG X CGA AGAAU 2911 @ACr=~ C 'I~M 1796 H.GAM6PR 1216 A1X~aW U x MiG X COA ACGA 2912 GCC A AACAT 1799 HSGAM6PR 1217 AUM=Ifl CUPLUM X CMA AU11CC 2913 CIMMAT A aAMAX 1805 HS.ATAPR 1218 AAOGfl CUGAL70A X OMA ~AUntwIA 2914 ATIAT= A A7ItC= 1808 , RM~6R 1219 A=fl c umum x aA AIXWXX 291.5 GMA' T CC~r 1809 HSGAA6PR 1220 U33AX3 amom x A AAMJA=l 2916 aCATATr C CATI= 1813 HgGAMPR 1221 CMEA CUALUA X OMA AIL33AMJ 2917 AAICCA T CO W 1814 HNCA.6PR 1222 AGUCAUM Lmpm x aA AAUOMW~A 2918 ATItCT C CCiI=c 1823 HSAT6PR 123 GA=f CUGAUGA X CMA AMU 2919 ~CA7Ar C @C I= 1829 , RSGMPR 1224 AGG CL70AtXW3 X CMA ACUflPL 2920 C0AAr T OLCCT 1830 HSGTASPR 1225 Aau= axx.I2 x aA A~uxM 2921 TCCXB= C CACCI= 1836 IH.TA6PR 1226 AGUMGA LXPxL x a A A0U0A 2922 TICA= C 'ThPcncr 1838 HSGAA6PR 1227 MAGMAGP UA~LA X CGA AMD =f 2923 CCLt'i= T Cn)EI= 1839 HSGAMPR 1228 CMAGxI CUC4Utx; X CA AGIGGM 2924 CACC!T C TAC7IM 1841 R93ATA6PR 1229 AILfl-AW arAuMG x OmA AGiM 2925 O'itTI= A ACICGA.T 1845 HS~kr6PR 120 AAxx=r CUMLU. x CcN AaUMA 2926 TwAcr c Ga WO 00/61729 PCT/USOO/09721 84 Table H. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1853 K9.AA6PR 1231 UUO=fl CUGAfLMG X C:A AMfA=t 2927 CAJ T GDCAGC 1865 HSGMATA6PR 1232 G33C2AG CLUAJDM X MM AUUUtJC 2928 -OCAAAAAT k Ci'it= 1868 HSGATA6PR 1233 LIM=~f CMfAMAG X 03AA AIJUM t 2929 AAAAACr T CtCCCAA 1869 HSG.TA6PR 1234 tIUGLXX3 Ct)3V-AG X CGA AAGUAUU 2930 AAMMCT C COtCACAA 1886 HS~kTA6PR 1235 tWDX.U CMUA X CYJAP AXS fl 2931 CAAA' A CAGCCICA 1893 HSGATA6PR 1236 CtCU CIUAG X OSAA AG3fLJA 2932 TACA=~ C AG33=X 1940 HSGTA6PR 1237 GLXrt= CUGI2 X CCAA ALDO=f 2933 GCCCA~AT C CCGA1& 1957 HSGATA6PR 1238 GAAUACUU CLIGUtP X CG A AGXU=U 2934 TGXP C AALiM=i 1962 HS-AM6PR 1239 GACCGA CtfALIW X 02AA ALUXIO 2935 GICAAGr A TIrC 1964 HSCTA6PR 1240 UrP= CUGD31AG X 0GAA AUAPCUMAl 2936 'ICAAGIAT T Ca3IMA 1965 HSGATA6PR 1241 CUtLMA=t CMAXAGL X COA AALMiCV 2937 CAA0rATfl C GOrCA 1970 HS9GTA6PR 1242 CCAUT!U MrAUISG X COAA ACGM.A 2938 ATI=.C AAA= 1-981 HSMM~6PR 1243 CCULM= CUGAUMG K OaM AC1= 2939 GAG r c T~A 1983 HSGATA6PR 1244 CfltCfMIf CGUGIG X CIWA AGG 2940 IGItT A CAM 1987 HSAM6PR 1245 CU3rPC CtL2AIGAG3 X C13A ADUAA 2941 -CIrA~a A GOOICAG 1993 HSGAMAPR 1246 GCNGA CtGAG1O X OA ACUCC.U 2942 ATG C A0ICIC3 199*7 HSTA6PR 1247 COA CLIa- X CA ALCflA= 2943 GC7 C I3CI= 1999 HSGATA6PR 1248 G3GM CUGAUGA x aIA AC4CLtMC 2944 GtCIGr C G0r 2004 HSGAMPR 1249 CGC CUGADM X CaA AG0A 2945 'T~CTC C GCO 2017 H.aAn6PR 1250 GA:' CU t X 03A AaX=t 2946 (COGA~ C ACX IC 2022 HSGATA6PR 1251 GCCOA C atXMG X OMA ACLAU 2947 A~CAI C CC=I 2025 HSAT6PR 1252 GUOCC CTMAUGA X (XAA .ALGiDMf 2948 @.AiG r C 03GM 2039 HSGAT.6PR 1253 GCCCG aXULXG X aMA ACCOGU 2949 G~ACO T CWItUI 2040 HSG~kPR 1254 C3ACA CGUGIA3 K CGA AAI03G 2950 AC0.Tr C CIC;= 2095 HSGTA6PR 1255 =- CLMLM K OM AGOCtttt 2951 GAG=~ C 30 2108 HSMMPR 1256 Aaxn~~; anXw~ x a3A Am 2952 Gca3= c ALIc= 2112 FSAr6PR 1257 CAOSan CMXIGAW K aA AGLXz 2953 GiCr7 C CACI=I 2117 HSGTA6PR 1258 GCGAA CL1AUA X COA KAflM;J 2954 ALIT cr C GI7GCI= 2122 HSGA6PR 1259 CAAc axWXPL X CMA ACCM 2955 ACTC=u C 7ITI'I 2127 HS~TA6P 1260 COACA cLIX20M X OA AGAGC 2956 ITG7C T T MGM=~1 2128 HS.k.6PR 1261 GC1CC CMUGA X C3A AGLkW 2957 GII=r T 7GG~: 2129 H3Wah6PR 1262 tmDXMC aUMxMG X CMA AAM 2958 iTiC rr T G0CA~k 2140 HSAT6PR 1263 ALtUJXfCu II; axom x A AaXXMC 2959 GAGYT C CAAC~ 2174 FOCTA6PR 1264 G32ACGL CMVWGA K CA ACA03r 2960 AA I= T CIrIOC 2175 HSA~M6M~ 1265 AGCM CtCAUGrx X OSA AACAJ 2961 ACI=' C 'ICG1T f 2177 HSGA.6PR 1.266 AA03= CLK;V)M X 03A ~AIkJXC 2962 GIGATIt'r C GIGtTI 2184 HSI!A6PR 2267 UCAAAUA aCumIG K 0A AGC~3 2963 'TmGI= T 'T.TrrIG; 2185 HSGAT6PR 1268 tUtCAAAAU CGUGtW X 03 AA03CXa 2964 CGIt3r T ATrIGA 2186 HSAPR 1269 UJ3LXOA CUPIPA3 X OGA AAGO= 2965 G00=T A TITIrA 2188 HGATAPR 1270 UtMCAA CtUGAIM X COA AUAM 2966 GOrrT~ T T13AA 2189 HSGTA6PR 1271 CfL'LJUCA CPOM K OMA AALMAAG 2967 CCIrAnTr T 1GAA 2190 HSAM6PR 1272 tflLVTX= cvmmw K aA AAUAAA 2968 CI'In=I T @AA~ 2202 Hs9AT6PR 12 73 UU3WAM CUAMA K COAA PAIAU 2969 ACC T TI'1tCA 2203 HSC.M6PR 1274 amooam aC xw. K 35A AA7tU 2970 G;M= T TrCW WO 00/61729 PCTUSOO/09721 85 Table Mf. Hammerhead ribozymes targeting GATA transcription factors (1. 2, 3, 4, and 6) and the complementary sequences 2204 HSCAM6PR 1275 tctumoaki CtvxiX x aA AA?~LxU - 2971 ~AAM= T WCOA 2205 HGA6PR 1276 CUCU=l3 CtO1?4J2 X CtA AAAACAL 2972 GAI'I T CCA)GP 2206 I-[G.TA6PR 1277 cattt.D CtX2.AD x oA AAAAAfl 2973 ATGIFI= C CCAAGM 2217 HSATA6PR 1278 LICAtr3L CUGflNX X CMA ?AXtEX!J 2974 -AALMO= T GJIGAAAG 2269 HSGATA6PR 1279 AGlGO= CMnA~MA X OaA .AL0DZC 2975 Tfl3fl= T G33CCr 2278 HSATA6PR 1280 (ra)3 C tX3 X 0:;A AGfL33tt 2976 G3ci =~ C CACA 2293 H.SGATA6PR 1281 CCCtt UUGG X t x QA AGOC030 2977 GCrtCt C C330O 2310 HSGATA6PR 1282 LTflCAAW2 CWrAtLr4 X OMA AGA33 2978 -ACCC=z C ~CriT= 2315 HSGTA6PR 1283 -GCJ~tLX CUGALGA X CCMA PLM 2979 WItA T CaGAG 2316 H.crATA6PR 1284 GaxUUan CMflAGl X 03A AAfl31ML 2980 CTCCALI C CGAGO 2331 HS&TA6PR 1285 CC== CUAc X CCA AGXtttf 2981 CCADGAA= A GaACCIGO 2344 HSG.AM6PR 1286 UaLAGO CIUGflAG X CMA AGCA 2982 ci7Mcr T ariwI 2352 1LGTA6PR 1287 At.LUXC CtxGixMG X OMA LAGCGC 2983 ~T'IC ' A T0AAA 2359 H-SGAT6PR 1288 Utt7JAA CrMMAG X CCPA AUX-CAU 2984 TAGAT A TINGA 2361 HSGATA6PR 1289 =tX==a CUGAUG X OGA AtLhfltk 2985 TOAT T CGPAGC 2371 HSGAM6PR 1290 L'UXIAAA a3M~X~ K A ArXrMn 2986 AGAGAAT T 'TrrAAAA 2372 H.GJM6PR 1291 UUtXJAPA CGUNG~ X CMA AAIUttt 2987 @GAAr T TITAAAAA 2373 HSGTA6PR 1292 LTXtUItA CMMA X CCA AM=J~t 2988 ACA T MW.AAAA 2374 R9S.TAPR 1293 CUuuutx CUAxUi X CMA AAAA=t 2989 GAGA=I~ T mAAMA 2375 HSCAM6PR 1294 trtXXUut CMAU1GAG X CM AAAAAI=U 2990 AGATrrrr T AAAAAPk 2376 HSGATA6PR 1295 AIXU=uu CUGAUGAG X aGA AAAAAAUfl 2991 GATiTi i A AAAAG 2385 HSGATA6PR 1296 AAAOA CtGAUGA X OMA AtYXTJUTUUU 2992 AAAAGA T TICA= 2386 HSGAZA6FP 1297 AAAL13 CMfAM X COA AAMUt=X 2 993 -AAA~AGAr T Tomrrr 2387 HGAT6PR 1298 CAAAALIOC mmucx~ X A AAAEXUW 2994 AAAGA=Tr T GTTIM 2392 H.Sa!A6PR 1299 L2C CL X-AMA X 03A ~AAAA 2995 TI'ICAT T TMIICCA 2393 H9RSGAM6PR 1300 UtXG~kA. CUXPLX X CGA A14flCJAA 2996 TrIG=T T 'IUMtA 2394 RgGAA6PR 1301 ULXUGtC CUAM X OM 2AA1GCA 2997 TI'iCa'r T G7CAA 2397 HGATAPR 1302 LrAXXMx CLUGAG~ X CMA ACAAAAM 2998 CATITIU C CAAM 2404 H9GATA6PR 1303 AGCACA CLMM X CIA ALWXXIt3 2999 3AMA C AIGT= 241.2 HSGAMA6PR 1304 AUCAGAAG CUGAEXW X CA AGAAJ 3000 CAG=~ T CIIGAT 2413 H9GTh5PR 1305 GAL2A CELOUA X CYA AGCC7 3001 A.ITGT C TCGA 2415 KSGAA6PR 1306 uumamc Ctxx~m x aA A=P)mc 3002 aIT'rCr T CI7I'TA 2416 HSGThSPR 1.307 ALXtPIC CIAUGAG X 03 AGAA~ 3003 ictrr C 'IGAT 2421 HS6R 1308 CCAAAAUU CUGLIAX~ K MA AIXCfAAL 3004 CI=I C AA~TIM 2425 HGA6PR 1309 ACACA C!LXCP K CYA AMCIWk 3005 TGM T TIM=I~ 2426 HSGA~6PR 1310 AACAAC~k CUALICx x aM AAIMtMt 3006 GA7CATr T 703r=~r 2427 M?3G.TA6PR 13-1 GACAAC CLIGALL X 03A AAAXItJU 300Y7 1tATr r T GGrIGTIC 2431 HGA6PR 1312 UMMWA CXIAMA K CA ACAAAU 3008 A~rri= T GIICA 2434 HSCTh6PR 1313 AAntrI= CUGAUGL K a:A ACA 3009- TIIG T CAGV~ 2435 HSGYIA6PR 1314 AAAUtL)= CVGPC2 K 03A AAAAC 3010 TI'GT C CAAIT 2442 HSG.AM6PR 1315 UAUGAAG. CUGZAU= K 0A NAtXZ'tlp 3011 7tCAAA T TIC'I 243 RgGAT.6PR 1316 ciUhi~AAG CtflMXJG K CCA AAUIX=ll 3012 CZATr T CrIKAM 244 RAT6PR 1317 GStflGA CMUGA K CCA AAAI~rMf 3013 avz C raAC 244 9GMT6PR 1318 A~AL U Ct)=[G K aA .AGVWX 304 kmk='rTc~r WO 00/61729 PCTUSOO/09721 86 Table 1U1. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 2447 HSGATA6PR 1319 AAG= CM.X1GAG1 X C~A AAAAA3U 3015 AAT'=I C ATfl= 21450 I-LMTA6PR 1320 OMAA S3 CUGrS1X.3 X CCA AIJGAAGAA 3016 TITr A CV1 'rrIC 2454 HSG-AT6PR 1321 ALGL~rA CtXGLMI2 X OMA AGSUffMf 3017 T~CrT T TIXM= 2455 HSGAT-76PR 1322 C.AIXMX CUr.AIY3AG X (XMA AAGGUIfl 3018 ~CCT T ICA 2456 HSCATA6PR 1323 GGAU=fl CMMAGi X CXMA AALIU 3019 AMCi r T CCCA 2457 HSGATA6PR 1324 tfl3.A=Xf CMLGAG X CGAA AAADO 3020 ThAtITI C CAC 2463 HSCATA6PR 1325 GATAItU CtUD&M X CMA AIL13OGA 3021 TICCT C CATI 2469 HSGATA6PR 1326 oncAmm wawmr.A x cA Amm.Au~f 3022 ACAGT T TCAT=I 2470 HSGATA6PR 1327 COCA=~ arwAG X CXMA AAUIUO 3023 'CA= T CKr G= 2471 HSGATA6PR 1328 APLCCAU CUGAMA X COAA AAAU=t 3024 COPGA=~ C ATGI=I 2480 HSGA!A6PR 1329 trtrcA= CMA3LG X CMA ACt~aM 3025 ATGI= T CAOGG 2481 HSGAJA6PR 1330 UtUUCCA Cx3AtXSi X MAA AAOCC 3026 T'1I0I C ATGGA 2493 HSC-TA6PR 1331 CCtrAAITJ CUGAGA X CMA AiUtUttt. 3027 GAAAA C ACTGG 2497 HSGATA6PR 1332 AUflXC CMfAMAG X MIA AG.1tU 3028 AGAICCr T GA3 2506 H93=r6PR 1333 GanJACCA CUOXIXMG X CakA AM=lXt 3029 GUM T TWM= 2507 HSGATAf6PR 1334 UG~nF,= CtL3UA X C@AA AAtUtU 3030 AGCCTT T GMCM 2511 HSGTA6PR 1335 GAGAUG CEMAUG X CrA ACCAAAfl 3031 CT='~ A CAtCA 2517 NSCIA6PR 1336 CCUCrtG CUMtG X 03AA AIXXXXIAC 3032 GIMCACT C WCIG 2519 NSGAT6PR 1337 AGM=~ CUGAMIL X CMA ?AIALUJ 3033 ACCA C iGGA= 2532 H.GA6PR 1338 CAACC CUGAUGA X CMA AMY 3034 GCIAr C LOUI -I dU 2536 HSGTA6PR 1339 AmttA= a)zA= X OMA ACGA 3035 cAGI=r T CAGA~ 2537 HSGTA6PR 1340 GCCU73 CIGAUM X CMA Mam=J 3036 AGICI C AMA=C 2545 HSGTA6PR 1341 tLraA4w Cn-AG X OMA ACUCAUG 3037 CMaXP C TC17= 2547 R1TATA6PR 1342 LmmtiAA CUMLXM X COA AGC 3038 TGG C 7ETCA 2549 HSGAM6FR 1343 uutJmfwI cu~miXA x CmA AG~~Lt 3039 AGII= T ATCAAAA 2550 HSGTA6PR 1344 AMILXGt armxwG X CA AAGAM= 3040 03ICII A TCAAAAAT 2552 HM6PR 1345 AfLMLXXj'uut ar AUIA X QCA AEUUVM 3041 TCITT C AAAAA=.. 2559 R9STU6PR 1346 MAM~IA CUGLM X MA IXfJUttk 3042 MkkAAT A TIDCCA 2561 HSAMIPR 1347 AACMEflw ax2UJGA X CCA XILJ!JW 3043 AAAA= T ALICI=r 2562 E9AM6PR 1348 AAPLUPLG CUCAIGAG x a2A AAUAUUUU 3044 AAA=~ A CrIorri 2565 H9G.TA6PR 1349 LICAALT UGAMIX X CGI ~JAGLMU 3045 A 'ocr C AITIGC 2569 HSGATAPR 1350 G~L1LX CUGt7.UG X OA ACIG 3046 TACIICr T TGAAA 2570 HSG5kPR 1351 AGEL=f CLUMLIMG X OA AACLMM 3047 ACirC;r T Gomm= 2583 RgGATA6PR 1352 mAx.G c aCLtM X COPA AUOCAX 3048 GACI=T T GIALrI' 2586 H9.Ak6PR 1353 GUUPAAG CUAx IGxG X CA XACAL~ 3049 'TIU= A ACITIA 2590 HSGATAGPR 1354 GLMXM CELMX X C)A AGXPLA 3050 TIAACT T 'M)CAMC 2591 IE~rPR 1355 tmGnA u CULTMGA X CM AAGX7KA 3051 TOM=CI T ACAMC 2592 NH.Ak6PR 1356 anLIA CaGUiM K CA AAAflXAC 3052 G1 A ACTAA 2597 HSkA6PR 1357- UtACl CUAMtn X CGA AIflJEMA 3053 TI'IACA~T A CAI7 2613 HSGMT6PR 1358 CvtLJ CtGAUGA K C:A ACUC 3054 ACIAMr T TCIAAG 2614 HR=6PR 1359 ACUUUGAG CUAnGA K CA AACG= 3055 CIM=I T CICAAADr 2615 HS GATA6PR 1360 AACUtG CIAUMG K CA AAACGUCA 3056 TGArr C TCAAGI 2617 HSCTA6PR 1361 tX2AA= UCAM XIIlL K PA AGAACOJ 3057 ACT'tI C AAA~rrCA 2623 HS;A6PR 1362 MACAMMM anqr.W X CIA AZJEXM 3058 cr~aPWr T a~iTI WO 00/61729 PCT/USOO/09721 -87 Table MI. Hammrerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 2624 HSGATA6PR 1363 OZa;L-V CUrAMOG~ X CMA AACUtfl 3059 'ICAAA=r C ATATI 2627 HSSATA6PR 1364 CCAACAA CMAMJAGI X 02AA ALr-L!JtJ 3060 ArGT A ITIG7= 2629 H.AT6PR 1365 ADOCAC CMfALMAG X OMA AIMA 3061 G=rIAT T arTG7 r 2641 HS3ATA6PR 1366 txAaMrxA CXAMAG X CXMA ALAQ 3062 '13CIA C TGA 2648 H.MAM6PR 1367 U= =U CMXAtfl X CMA AL JtJCA 3063 TCTGACr C MTCOA 2652 HSGAT6PR 1368 CAAADt= CUGIflK3 X CMA ACtLrA=U 3064 AAGIC= C GSATI' 2658 H=A6PR 1369 ELXXXM C3tLrA X a3A AtMMtC 3065 GMAT~ T =AC 2659 HR9GTA6PR 1370 CtlUUUThC CUCIA1L X 0AA AAEXXtA 3066 ECrAATr T GTUAAG~ 2662 HSGATA6PR 1371 ALttfla t CtXWX2 X CCA ACAAAIJEC 3067 GA1T A AAA 2671 I-LGATA6PR 1372 LXXXXXIO CUAx=t X CXPA ACtfLU= 3068 AACG= A CCAACA 2683 HSMMT6PR 1373 AAG~AAAA CtMADXM X CCA ALM=~X 3069 AACAAGAT A TrI'III 2685 HSGATA6PR 1374 GSAAAAA CtflAI X 03PA AIIALt= 3070 CAGTA 7TrI= 2686 H-c.Th6PR 1375 tJMAGA CGUXIA X OGAA AAUAtttX 3071 AGTA~Tr T TI~I'It 2687 HSMMT6PR 1376 AUGGAAGA MGM=3 X CA AAAL= 3072 IAA~TrT T WItT 2688 HS-,;A6PR 1377 CAUrJSAPA CMflEIG X CSA AAAAIIr 3073 GATA=Trr CrC 2689 HSC4M6PR 1378 ArMCA CUM'= X 03A AAAAAIUIJ 3074 ATAT=I C T~TCC 2691 HSCAM6PR 1379 ALCA CrA~IXM X OM AGAAAAAIJ 3075 ATI'IIC T CCAU,=7 2692 HSGA7h6PR 1380 M~IA=f CMWI X CCAA AAAAAA 3076 TrI~rI' C CAMIurx 2698 HSGTA6PR 1381 UtUnt= CMALMtf X 03A ACAGGA 3077 TTm .'iar A 1TAM 2700 H.rAM6PR 1382 AMIJMIUt aUQMin X CMA AAIUO 3078 CCA= A CA~AT' 2705 H=6PR 1383 AAMAAAAIJ CUL-W)M X CZAA AUUGUAUIL 3079 TA33CAAT A A~rrrrrr 2708 HgGAMPR 1384 UUtUAAAA CUALM X CGA AUtA]tGJ 3080 AC.ATAAMT TrI9AA 2709 HSA~6PR 1385 UUtXUAAA axmix2 X 03A MAUM=~~ 3081 CAAT~ T TITAAA 2710 H9CTA6PR 1386 uuuuaAAA CGAUGAG X CGA AAAfLXM 3082 AM =AIT T TrThAMP 2711 HG6PR 1387 CVEXJU!AA CtGAI= K A AAAAU1JUI 3083 ~AIAArrr T 7MAAAG 2712 HSGATA6PR 1388 ACUxxAt CLGAU= X CA AAAAAILtA 3084 TAATrrrr T TAAAA~r 2713 HSGAI.6PR 1389 CALUUUU CLGUGAG~ X OMA AAAAAAIXJ 3085 AATrrrrr T AAAAAIG 2714 H~SGA PR 1390 GCACUUM C~rz3)= X C3;A AAAAAAAU 3086 ATIII A AAAI= 2726 H.GM6PR 1391 GCA CtXGIX= X CCA ALXXXMU 3087 AGI7GA T 'iGrI= 2727 HSMMPR 1392 UX2UA CLtXW1GLG X CIA AA1XA 3088 GCIUC= T GOI=I 2732 MMM5PR 1393 xmm cuwnw x a2AankAAU 3089 A~rImr T G~aAT 2741 Rqm6PR 1394 um~a an~rx X CCA A)==l 3090 G~akm C AMIMA 2747 HG~kPR 1395 AALIXXJ aXLI =X~ K A ACrCU 3091 ATCAIGT T AAA~T= 2748 HGkrnk 2396 A1AfAGXJ CGAUGAG x a2A AALCA t 3092 ICIAI' A AAT1C.TIT 2752 HgMIAPR 1397 IAIJAU CXLPLM X COA AWXJUA 3093 7G~nAA C ATIICAT 2755 H~SGAAPR 1.398 CCAL3 CUAIML K CGA AL3ALIEM 3094 TAAAa=.T 7 TCX 2756 HSMA6PR 1399 tmwLP CUX2IXPL X OMA AAUGAEXX 3095 AAA=~ T GCTG* 2761 HSAPR 1400 UtMALi CUAUixA X CGA AUOCAAU 3096 AM =I~ A G~kTrA 2766 HSGA6PR 1401 L13a)Oxw7 CUGAUMG X CM ~A IUA 3097 @nM~AGA T TAC~ 2767 N.-.aM6PR 1402 AM =n~ CUGALIMG X OM AAUCCLIAU 3098 AAG 'r T ACOG 2768 HSG6PR 1403 AA~aXlJ COGADMG X 0A AAUL 3099 TAGI'IT A ACAG= 2776 HSM6PR 1404 uw .A an~m K CCP A1fX 3100 AAM T ITrIMA 2777 HRkMPR 1405 AflUAA CtLUg K C:A AAItfl 3101 AC43 T FDMAT 2778 H9MMT6PR 1406 C&JtLXMIA CM MA X CC AAAID=f 3102 a~'IT T T1nW ZI WO 00/61729 PCT/USOO/09721 88 Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3. 4, and 6) and the complementary sequences 2779 HSGATA6PR 1407 CEAUUAIA CUGAUGAG X OA AAA1GCU 3103 AGCTIT T TAA'IG 2780 HSGATA6PR 1408 UUCAUUAU CUGAUGG X CGAA AAAAMIf 3104 TITT T ATA'IGAA 2781 HSGATA6PR 1409 AUDCAUUA CLAUGAG X CGAA AAAAAAM 3105 CTITITr A TAAGAAT 2783 HSGATA6PR 1410 ACAUUCAU3 CGAGD X CGA AUVAAAAA 3106 TITrIA A AGAA'I 2792 HSGATA6PR 1411 AAAAGXU CUGAG X C2A ACAUCCE 3107 A'ITGAAUr A AACATIT 2798 HSGMA6PR 1412 UAMG A CGAIEJAG X CGAA AUGWUAC 3108 GrAACAT T TMACITA 2799 HSGATA6PR 1413 UAGA CrAU. X CPA AM UJtA 3109 TAACATr T TIAA 2800 RGTA6PR 1414 AU=G aGAG X CAA AAAUU 3110 AAACATIT T AACITpT 2801 HSGATA6PR 1415 CAUGAWGU CUGAGG X CGAA AAAAIfU 3111 AACMTIT A ACITPA'G 2805 HSGATA6PR 1416 aAmpU CUGnAG x CGA AGDuAAAA 3112 TITDACr T A'IGC 2806 HSGAT6PR 1417 GUACUE CMUGAG X CGA AAGUAPA 3113 TrCIT A AGCr 2812 HSGAM6PR 1418 AUXJUUAG CUGAUGAG X CGA ACCAUUAA 3114 TMAMGT A CITPAAAT 2815 HSGATA6PR 1419 ADMADPUU CLGGAG X CGPA AGUMEAU 3115 AIGGC T PAAATAAT 2816 HSGTA6PR 1420 AAUALUU CGAUAG X CpA AGM=A 3116 'IMCIT A APATAMT 2821 HSGAA6PR 1421 UUUEAPAU CrAIMA X CIMA ADOLXAG 3117 CTMAAAT A ATrrAAPA 2824 HSGATA6PR 1422 U tJ XA CUGMDGG X CMA ADUAUMUU 3118 AAAATAAT T TAAAGA 2825 HSGATA6PR 1423 UXJtCUUU CUUGFDG X CGPA AAUXADOU 3119 AAATT T AAAAGAAA 2826 HESGA6PR 1424 tUUCUtJ CGAUGAG X CGPA AAAUAIXU 3120 ?ATATIT A AAPGAAA 2839 HSGaA6PR 1425 MEUAGU CIAeM.G X OpA ACAUUU 3121 AAAAMA= T AACDGA 2840 HSGMA6PR 1426 GUCUAAGU CUIL;G X COPA AACADUU 3122 AAAMTG~r A ACINGAC 284 HSGAT6PR 1427 GAAtDCU CapG X CGA AGUUACA 3123 ' cr T ?~CATIC 2845 FSGAG.PR 1428 AGAUGUC CtLWGp X OpA AAGUUAC 3124 GTMACUT A GACAIc 2851 SGMA6PR 1429 AGCADAAG CDA G X CPA AUG[JAMA 3125 Tn.MT T Cr=r 2852 HSGA6PR 1430 AAGCADA CUGAmG X CGPA AAUGUCUA 3126 TGAT C TIG 2854 RSGTAPR 1431 AGAAGCA CtGAMAG x QAA AGAAIGM 3127 GATI= T A'IGCI 2855 HTA6PR 1432 AAGPAGC CUGAXMW G X oMA ADAMXU 3128 ACATICT A 'TlUIT 2860 HSGATA6PR 1433 30APAG CUGUGAG X CMA AGCPAAG 3129 CPM T CrrACA 2861 HSGA6PR 1434 UXIGAAA CULINUW X C3PA AAGCAUAA 3130 TEGIT C TrrIACAA 2863 HSGAM6PR 1435 AGLXA CzWXMp X CGRA AGA AU 3131 AIGC=r T TnCPACr 2864 HSGMA6PR 1436 UGXUiA CLmG. X CGPA AAGA 3132 TiCrIt T TACAPCIA 2865 HSGM6PR 1437 GUCGKlJ CUM]G X COAA AAAGAME 3133 OInInT T ACAC 2866 HSGAT6PR 1438 3U3POXI CUM= X MpA AAAAGIW 3134 CIIIT A CACnDCA 2872 HSGMAGPR 1439 AIom CwEmG X CGAA A==3AA 3135 TCA r A CM C 2876 HSGTA6PR 1440 UAPAIHM apMnG X pA ALIPI XJ 3136 AACDnAT C CCITA 2881 HSGA6MPR 1441 AAA1PA aosmG X CGA ALZM;= 3137 CIIIT T TITALTIT 2882 HSGMA6PR 1442 GAAMUA CosmG X OAA AplXZU 3138 AHATr T nTIIC 2883 HSGTA6PR 1443 DMJAAI CGAG X oA AAAXZ 3139 1' IT T ATMTI 2884 HSGA6PR 1444 !)AA0AIA a IMG X OpA AAAM= 3140 C=CTI A TUTICCA 2886 HSGMA6PR 1445 AUXuPA axmumG x CGPA AuAAAw. 3141 CMT=IT A TIcoAT 2888 HSGAT6PR 1446 CAAUt0A CXsDMG X MpA AUUA 3142 TIDUMT T 'ATIG 2889 HSGMA6PR 1447 ACAAU30 CUGALUG X CGAA AAULAAAA 3143 TMDTr T CCAI' 2890 HSGMA6PR 1448 AACAIXIU CUGpMpG X 0pA AAAtmIUA 3144 Tn ATrr C CAATIGIT 2895 HSGATA6PR 1449 uCxUAAC Cxxm3G x GaA ALAMMA 3145 TIT T G 2898 PR 1450 u UUCGP aDGG X CGA ACAX 3146 CDATrGT T AAAGAAAA WO 00/61729 PCTUSOOI09721 89 Table III. H-amnmerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences I2899 HSG~qA6PR 1451 Luuuxu CU3AMwr X OSA AACAMIMf 3147 f V.IT A AAGAAAA 2909 HSC-ATA6PR 1452 tLUXAPA CMXAMA1XL K GA ALXU=~~t 3148 ?AGAAAAAT A Trr-APcA 2911 HSG.A6PR 1453 GE=XrA CUGGAMA X CCA AM=It~Xt 3149 AAAAA]TAT T TCAGA 2912 MATA6PR 1454 UMX=U aU2llMMA X CO.A MAU=U 3150 AAAA=1d T MAA 2913 HSG..TA6PR 1455 mu=fJCt arU-AD x ~ai AAM.MLWX 3151 ,AAATM iTr C AAkA 2924 HSGATA6PR 1456 tflAwAAA cummfl. X OmA NUtLJE 3152 GA1ACAAAT C TMTCMI 2926 R93GATP6PR 1457 CanAGG CtCfl X O:A AGUUUJ 3153 Af-AAAM T CM7:PM 2927 R9S.TA6PR 1458 LIMLGAG CSAUMG X OCA AAGAUEMf 3154 (CAAT C 'r=Mk 2929 H3MiA6PR 1459 MMMtfl C!nAMAG X OMA PA~IntJ 3155 AA'IC1't C ITCA 2931 HSG~AA6PR 1460 AUrtj anNXIG X CC;A AGCAC 3156 TC~iL~r C AGAA 2940 NSAM6PR 1461 AGAAAGOC aYMAGX X OMA AUUtXt 3157 ADG.AAAT T GIir 2945 HSCATA6PR 1462 AAMO~k CXMC; X CDA, ADGJCIAtJ 3158 AATI='C T MM=~ 2946 HScATA6P 1463 AAAAGA CLXAMtfl X (XP.A A~AGOAJ 3159 AMU=r T CICTr 2947 HSGA2k6PP. 1464 CAAUG CLtXAUGAG X CCA AAGGCA 3160 TIUCCTI C ITI 2949 H.9GATA6PR 1465 AAAAIA CUAU X OMA AGAM 3161 GI'I'It C MTIUI 2951 HSCAMAhPR 1466 tUt~.ACAA arAMXGL X Om 1AGGA 3162 CrriIc A TIGIM~ 2953 HSG..TA6PR 1467 tuaxwL) CtuaL1m X omA AM2GA 3163 MI=. T T(mMAM 2954 HSAM6PR 1468 tJUCUEAC CMUMAIG X 03A AUAGA~ 3164 =IIATv T GITMAG&A 2957 RH'AM6PR 1469 AUELICtJ CUMMAG X OA APUA 3165 crATriar T AAGAA±T 2958 1HSGATA6PR 1470 AAAAUICtfl CU3IflML X 03A APAAIU 3166 mTrT=II A -AFI 2964 RSGATA6PR 1471 tUMIA cuZoImG x aA AUtJEXWAA 3167 T1MAGfAAT T Trwc 2965 HSAZ6PR 1472 UtX;VPA CUGXUGAG X K AA AA1XCXM 3168 MAA T TMONMI 2966 HSGATA6PR 1473 CUL13UAM CUGAUGAG X CMA AAA1JtUJ 3169 AAAATr T TAAN 2967 HG~6PR 1474 tUtUUUnL CLXW X CMA AAA1 3170 ~AAA= T ATAAAG 2968 HSG~A6PR 1475 UUCUUG~ CMAtnAZ X CGA AAAAAtXC 3171 GATI'1' A T~ACP 2970 j FA- 6PR 1476 ILWfl~f axmXPL X o3A XAAAAD 3172 AT=IT]T A CAA 2984 HSGM6PR 1477 AM33 anwxmG X ccA AXJ== 3173 AMCCAT A MMt= 2986 HGTAPR 1478 AAO= CMUGAw X CNA 2AIINIXI 3174 AC;A A COX=rr 2993 HGAMPR 1479 G~AAA ajum X C~A Aaoa 3175 MU= T TA'IT= 2994 RTA6PR 1480 A~IAAAw aCmUGAG x aiA APa33J 3176 ACOM= T AT=LI 2995 ESAT6PR 1481 CAG.1AM~ MIUP1AG X CA AA= 3177 CCO A ~CI 2997 1R.~.6pR 1482 C;OkapA anv~cm x CCA ALMAM 3178 =r=~A T TMCIUI 2998 HSM~6PR 1483 cau CaEXpL K aA A~AnW 3179 C~1Ir T - EIGI1 2999 RMAMM 1484 ImJ~cyw arA1XPL K c3A AADAAAG 3180 CrI'1r.TIT C T A 3000 HSG~6PR 1485 T.xm= anuxm x a AAAMX 3181 Tr==rr A CIMIPA 3010 HS@.U6PR 1486 cmm a.nn x aPA AXtM 3182 TMOMAT A 41IM 3025 HRMM6PR 1487 a~xnx= antLIXAG K 03A AXUXUXX 3183 GANWA T GMM 3037 HmrA~pR 1488 Aomwm cumzwX K aA AMLU=Xl 3184 AMA T ri;CTA 3038 HS6PR 1489 UAGOMM~ CLXPL=G X CA AJALGlU f 3185 ~oCAACA T 3039 NS-..T6PR 1490 Utva]PG auIxam x ccA AAW=XI 3186 AACL'r A C~ 3042 HSUMPR 1491 c~xmm anxwIX. x a AGMAAJ 3187 ACrr=C A 3046 HSGA~6PR 1492 CLU - KUALA X A AGMC 3188 TACM= A ACMM a3053 I-LA6PR 1493 ~AAAAU C~UP K C3A AUCGX 3189 MA3M A GOIT 3058 HSAT6PR 1494 tWJWM MMUIA X CMA AUXEr1 3190 -r T kG= WO 00/61729 PCTIUSOO/09721 90 Table III. Hammerhead ribozyrnes targeting GATA transcription factors (1, 2, 3, 4. and 6) and the complementary sequences 3059 HSG-AM'6PR 1495 GJLXT= CM.AMXAG X CGA AALX13= 3191 AAM'r T GIrAAMC 3062 HSGATA6PR 1496 PGJAnu C[JrAWP X CGAA ACAAAL10 3192 GCa A AAI= 3066 HSGATA6;PR 1497 ACMWG~ CMflAIX X CGA AIJULMCAA 3193 'rITGrAAT A CI~rGG 3069 HS@ATA6PR 1498 CAL= CflAtfl X CIMA AGUMM 3194 TAA r C TA = 3071 HSGArA6PR 1499 CAu c CM fl X (IMA AGAUAU 3195 AAWIA T A GWntI 3075 HSATA6PR 1500 UUUACAGA CLAA X 03A ACtCLUA 3196 CICLA= A ~TCIGAA 3077 HSGaA6PR 1501 t~UGMN~ CMAUGA X OMA AL~cttWG 3197 Cr13T C TGZA 3081 HSGATA6PR 1502 AGAG=U CUAX~ K QA ACAtCkz 3198 GrAT A AACAC'I 3088 HS3A6PR 1503 CUtMAIJ CMXWriAG X CGA AGX7JtUak 3199 MAACACfl C MAGA 3098 HSCAM~6PR 1504 ACUUC CUAULGA X COAA ~ACUCI 3200 GkG~. C MM=A~ 3102 H-rAMA6PR 1505 UCA M ClALMPG X CMA ACAAXJ 3201 AAGIr= A ']AIGI 3104 HST f6PR 1506 AGCAC anuxpG x aA ALUCAC 3202 MCtI=. A G7GTGACr 3113 HSGATA6PR 1507 CUM=~ CfLr-AUC; X COA AGCAA 3203 GIVIC=L A ACCACA 3128 HSGAT6PR 1508 UXJAAACC CtXA~.X~ K MA ALtU 3204 AGCA T =%;CA 3132 HSATA6PR 1509 UUAAUGUlA CAxiCiG X CtPA ACLA 3205 ?ArI7 T T TAA 3133 RW~A6APR 1510 AUUAALU CE GAMAG X CGA AACCAACC 3206 GGnrI=r T AC~AT 3134 H.SrA6PR 1511 AMAM ax~mC xJ~ K A AACCAC 3207 WrI= A C~AT r 3138 RHAM6PR 1512 AAAAAAUEJ CMtAnAG X CMA AUGUAA 3208 G79M= T AATI I 3139 H-9MM6PR 3-513 AAAAAAAU CUSAUGAG X a3PA AAL13LAA 3209 TIM%=~' A ATITr=I 3142 HSCAM.PR 1514 AAAAAAAA CL)g X CGA N~A tflJU 3210 ACTIAAT T Trrrrrr 3143 H~sm PR 1515 AAAAAAAA C ULXMG X COA AAIJUAU 3211 CATnka= T TITI'IT1T 3144 HAA6R 1516 CAMAAAAA CUAV= X C1A AAAUtUAAU 3212 ATnAT= T TrITITI 3145 HSGAT6PR 1517 UCAAAAA CU IX X CCA AAAAfltAA 3213 TM =T~ T TIrrMtk 3146 H=6PR 1518 tLXAAAA CMfJIflMI3 X CM AAAAALXVL 3214 'mATrrrr T TrrriMA 3147 HSAT6PR 1519 AUUAAA CUAU= X CMA AAAAAAUU 3215 AAaT=I~ T Trr@.AT 3148 HSMTA6PR 1-520 CAUWAA CUAxLi X CCA AAAAAAAIJ 3216 ATIr T TrlIkaAG 3149 HSGATA6PR 1521 CCAIE2A CUALM X OA AAAAAAAA 3217 m'rrI= T TIXM= 3150 RSAT6PR 1522 CCCAUUCUIXO L X GA AAAAAAAA 3218 'TrITr T TMA 3151 HGAM6PR 1523 L~XDCC aXLIC X CGA AAAAAAPA 3219 TITrT= T GAT~ 3163 HSR 6PR 1524 LX00UW CLISMtXMG X CA ACU 3220 'GI= C CLXGA 3166 HSGA.kPR 1525 GSXX CtGAL3M X CMA AGGAAER 3221 @GIUIT A 7GNa 3176 HSGAM6PR 1526 U03LIGAM CIAUGiG X CIA .AnGrXX 3222 GGAA A TrCA~ 3178 HSGA!MAPR 15277 LrIxUUS CaX2G X CGA AUAGGUUJ 3223 AAC= T TCCA 3179 HSG.Ak6PR 1528 CUUG C!XPL X COA AMAGGEU 3224 AACTh.T T CAXM 3180 HSG.Ak6PR 1529 ACtxUCn CUMD= X CMA AAAMCM 3225 AC~n= C ACAM 3189 HSG.AM5PR 1530 AUfltXXXA CUGAD=~ x a2A XAtEC J 3226 ACG~ T T AMA 3190 HGA6PR 1531 LXXXXXP CtLXX2G x aA AALtr M 3227 CCorrI T ThAAAAA 3191 HSC.Ak6PR 1532 UrUixxxxi CLX;VXPL3 X CA AAAC=Lf 3228 CIG= T AAAAAMA 3192 HSGATA6PR 1533 UUUAUUUw CUGAMZG~ X K AAAAL!L 3229 ~AGAG r A AAAAMAA 3198 HSgITA6PR 1534 ACCtCtJXt CLGAUGA X OGA ALXXXXIAA 3230 TIrAAAAT A AAAG~ 3207 ,HS2AIASPR 1535 CAAAACAA CU-IXP X CAIA ACCCrUtUr 3231 AAAG3T A 'ITT I_ 3209 HSGATa.6PR 1536 GAAAAC cumIflw x aA ALUA XJ 3232 AP 1 GI= T arrIIIG 3212 R9MM~.PR 1537 CGAI@A CIGA X CCA ~AA 3233 OGMI= T TIG7CI 3213 HSGAM6PR 1538 Aar~ amumG~L x cuA AAw 3234 ir TIcIr WO 00/61729 PCTIUSOO/09721 91 Table Ill. Hammerhead ribozymes targeting GATA transcription factors (1, 2. 3, 4, and 6) and the complementary sequences 3214 HSGATA6PR 1539- OCA C arxAMix X CrA AA1ACAL 3235 MNTI'I T G7CrICI 3217 HSGATAGPR 1540 GUAtGA Mr AMAlG X CCAA ACAAAACA 3236 'IGr=rI cr.7iC 3219 HSGaA6PR 1541 CLXM C Ufl A M~ AX X C3A .ZPGACAAAA 3237 TITIGIC T CrIMCAG 3220 HSGT6PR 1542 BLIX;MM CUGAWAG X QMA AAACA 3238 TrIGITI C rG1 G 3224 HSGATA6PR 1543 ACLX=c CXAUMG X CIAA ACGAG 3239 'IC'IWI A CAIGi~r 3233 HSGAM6PR 1544 ~AOGD CtXAM7iAG X QPAA ACE)Ctf 3240 CAGIGA T OT~trl 3234 H9AM6PR 1545 .AAA CtflAI x aIA AAC~UCA 3241 AGTGIT C Cricrr 3237 HSGATA6PR 1546 CGAAA= CMM X CGA AGGAALUC 3242 GI'Iwr T CWI'ITI 3238 HS~TA6PR 1547 tLWAAAGQG CtMD X OMA AAGGAACU 3243 AGrwr C crr 3242 HSGCA7A6PR 1548 GCLAXEGA CtrAt).AG X CMA A3 3244 C~rIcw T TICAAAW 3243 RS=AA6PR 1549 AGCUUMA CttAWAG X COA AA30A 3245 CI'TC=c' T 70AAG~r 3244 USGATA6PR 1550 AGUUf CMIAMAG X 03A AAGOGA 3246 TtttM=I T CAA=r 3245 HSGATA6PR 1551 AAAGJU CUAMA x C2A AAAflO. 3247 ITtC~rTIT C AAADGrr 3252 HSMziM.PR 1552 tPhAAAC. CMfAMfl X COA AGLXUTM 3248 TCAAGI' T ITr 3253 H9MMT6PR 1553 .AIJAAAAG CGAI~k X OMA AAGUUJW 3249 C~ADI' T Crrrr= 3254 H9GTA6PR 1554 CIMAAAA CGAMAG X 03A AAAUtCtJ 3250 AAArrr C I

T

rrIT 3256 H.GAA6PR 1555 AIJAAA CUAn GAx~ X AA AU 3251 -ZDT=t T TrM 3257 HSGATA6PR 1556 CACAUAA CLMA x aA AAA 3252 ozr'irr T Tn~U 3258 H.AM6PR 1557 ACAGAUA LIMAG~ X QGAA MAAAAA 3253 CI'IrIT T TAM=G 3259 HSCAM6PR 1558 UACAGCA CtaALUAG X (JmA AAAGAA 3254 ITIM=I~ T ArOCIGU, 3260 HSCTA6PR 1559 MAO CUGXUGAG X CIAA AAAAGA 3255 TICTIr= A 70MA 3267 HSGATAPR 1560 UAUM CIGAUGc X CCA ACGA 3256 TA70= A TGIMCM 3275 HR9Ak6P 1561 AAUZVrtM CD~L X C3A AGIM 3257 ATGI7CI A TAG 3277 HRLrA6PR 1562 ILrAAM=f LCZW~ X COA AUAGPCC 3258 GIA= A GA'I= 3281 HSAAPR 1563 LP~tUGA CUMLcM X CMA ALPUA 3259 CrUMGT A TIAA 3283 HMM6PR 1564 UM tAM CGAGA X CGA AUAUflAJ 3260 ATAGAMT T MIAMA 3284 HSGATA6PR 1565 UtXMBMfl CGUGIG X CCA AAUAUlM 3261 TAA C ATMAAA 3287 H.SL1~.6PR 1566 txnmp.~l CUGAUC X OMA AUMALWJ 3262 AM=~. A TIAAAA 3289 H9GaAk6PR 1567 PACXnhJ CUGAUMG X CCA AMOCAU 3263 AMC=T A AACA. 3309 H9.Th6PR 1568 A1U1IG CLINXwi X COA AMX 3264 CUIkAr T 'IAAAT 3310 HSGAf6PR 1569 CAunnX3 cumuo x aPA AACUtJC 3265 G~rr T G Zkkkk 3321 HSATAPR 1570 Aa~x axpwGAG x amA AXXXXT 3266 AAAA=~ T mAAG3C 3322 H9OMPR 1571 AGOJ CUAUwx X CMA AAL1WX 3267 AAA=T T AAO 3323 H9GAT6PR 1572 GAAG v CIAUGA X COA AAAG= 3268 AAIGrr A tric= 3330 HSGTA6PR 1573 tXXPAAM~ CUAUzIA X CMA AGP XV 3269 TAGO T C~rrAA 3331 H3SGAAPR 1574. UUL13AA amntr. x aA AAGO3 3270 AAG3IT C CITAA 3334 HSMM6PR, 1575 tnUGxUU CLAuIGW X CakA AGGAA= 3271 WCMCCi T TCA~ 3335 HSiTA6PR 1576 ALIOCEXn CU XW7GG X CGA AAGGAAM 3272 OrWI T CAAGT 3336 HSGA6PR 1577- UAL70=J CxLA X CGA AAAPGA 3273 CIT I'= C AAPMM 3344 Rg.TA6PR 1578 AAAPGA CUGAUGAG X CGA ADOCUMI 3274 CAA A GtTIT 3347 HSCLEA.PR 1579 trcAAm CXMIxNG X 03A CtUU= 3275 AOG1' C CI'ITIO 3350 HSGAA6PR 1580 032CCCA xGAUGA X C3A AGACIU 3276 AIG r T MGM= 3351 HSTAM6PR 1581 C33C= CUMOUG X 03A APGACt1A 3277 TIGFr T 13A= L3352 I RIGM6PR 1582 Am =~ ctxr= x a AA~a w 32-78 AGM=C-1 T W.C WO 00/61729 PCT/USOO/09721 92 Table Ml. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 3]361 HSCATA6PR 1583 AGLMA CMfALUAG X CrA ACDGtt 3279 OSAMt= T T=A=c 3362 HCAM6PR 1584 AACXXF;C C .XAMXAG X CMA ACO) 3280 G(GC=I T (GIAccr 3366 ESGATA6PR 1585 AUMAAM CMAMI37 X QGAA ACCAAAG 3281 07rIr= A CCrrr= 3370 HSGATA6PR 1586 AGLMP CfLr-XXGA X COAA AGUA 3282 TGM T T~MTCr 3371 HSGATA6PR 1587 AAGAAL~ CtAUGAi X crSM AGG= 3283 07=1'r T 'TCCIT 3372 HSGATA6PR 1588 CAAG JW CM X OMA AAAC= 3284 GrACI'I T ATACCTIM 3373 HSGAA6PR 1589 CrAUO. CrUCIG X CMA AAAASM 3285 TACCITI A I'IC= 3375 HSOATA6PR 1590 AGCAW C!)PIA3 X COA AU~AA 3286 CCTI'T A CtTI=t 3379 R90ATPA5PR 1591 AAIJAAOCC CtLi?4XiD X Cr.A AGGOAUAA 3287 TrIAT= T G(r=I 3384 HSGATA6PR 1592 CUUCAAAU CMALUIG X CXIA ACtAG 3288 CtTI=r T ATrG 3385 R9SGAAPR 1593 ALUEMAAA CMflPMXG x a!A AACCA 3289 CrI'I= A TI'GA Gr 3387 R-9GTA6PR 1594 CAALUJt2 CLIAMAG X CMA ALU)LAt 3290 TGOU=I~ T GAAGrIM 3388 HSGA6PR 1595 UrAActx CUGALUA X CGA AA~kA= 3291 C=Tr T GAMMA~ 3394 HS9LITA6PR 1596 CAxnnx CLILA X CSA ACUtCAA 3292 TIMO0 T C.ACJG 3407 HSGM6PR 1597 taUAMA CUIGA]AG X OMA -ACIf 3293 CATG= T AGTMMI 3408 HSGA6PR 1598 GUGLAC CPMAG X CA AACC= 3294 A703=r A GI'InEI= 341-1 H.9GA'A6PR 1599 AGAGUAG CMAXMG X CMA ACA 3295 GIgr T ACrAI= 3412 RSGAA6PR 1600 CGAUA COGUGA X CGA AACAAM 3296 GGrnGrr A C7CI= 3415 H.SrA6PR 1601 AU0AM CLEAUA X COA AGAAU 3297 M~GM=C A CTCI=. 3418 HSGTA6PR 1602 CACAUG CxMACA X CA AGLGUA 3298 T=l rC C ITCdC I 3420 H9I7M6PR 1603 t.3CAAUl CUAUGA X OMA AGAGUAG 3299 ACJIC= C CAGI 3430 HS~kTMPR 1604 CrIGcc CUGAUGA X COA AMC= 3300 A==U~. T G3SAA 3440 HSGATA6PR 1605 CUMIAA CUALxw X CGA AIGCI1 3301 G3A T TrBUMMA 3441 HSATA6PR 1606 ACUtUM.PA CUMXMA X CMA AAC!Ut 3302 ~2GGAC T T TMLA1I 3442 HSGA.6PR, 160 CAUUtW CXLIXPUGA X CGA AACE= 3303 GAArr' T TAV 3443 HSOTA6PR 1608 CCAJtWA CMUAGJ X 03A AAAALtflJ 3304 AoCAG= T AAGIM 3444 K9S.Th6PR 1609 OtcUam anumXr. X IA~ mAAX 3305 avIrr1 A MAG 3446 RMUMhPR 1610 tXOOZA CaVWIW3 X CA AUVAAAC 3306 arrrrAT A AGG3A 3460 H-qGTA6PR 1611. AIAt~u cuagiXM X CmA AGtttJ 3307 GLV cr C AGM=7.. 3464 HS.Th5PR 1612 uwLAtxA aflAuiX~ =A .ACM~X= 3308 GACir A 'rn'i 3466 HSF PR 1613 AAMMtAtJ CUAU(2G X (3PA A1MCUG 3309 C1TCA= T ATM 3467 HSM~kPR 1614 A~W.P anWXL X aPA AMAaM~ 3310 MAG A TMV=r 3469 HSI~PR 1615 tLM~mu am1upL X COA IAW3U 3311 AGk T AzTr1m 3470 HSAMPR 1616 C~~.aLXAAA LggG4 X COA AANAUA 3312 GI7ATM r A M.TIGAG 3472 HGA6PR 1617 AUtICAA CUGLIML X COA AIMA~AUW 3313 AT7.TA. A TrIGAGAT 3474 NHLA6P 1618 tULfl= CUGAVGAG X CIA AUAUA 3314 7A IA T TGGU 3475 1SGTA6PR 1619 AUCALIL CLUVJ4A X 03A AAUUPMA 3315 ATM=A~ T GAUM 3484 HSGAM6PR 1620 AAAL10CE COGArGA K CM AUCAUfl 3316 CAkT A AGO=' 3490 HSGATA5PR 1621 CCAAA CMLO K CA ALICL 3317 ATk%=. T I DI~Rri 3491 1SGTA6PR 1622 OCAA~ CLGUA X CCA AAEM CP 1 3318 MkA= T IU1''I= 3492 HSGTA6PR 1623 Utr=%W CUMLIM X OaA AAALTX 3319 AGIT= T GTI3G 3495 HSMM6PR j 1624 jnt~ umX=M KUM X :A ACVAA 3320 a.Trrt T 'i3MA 3496 HSGATAPR 1625 gutU~CCC Kn= X :2A AAAAI 3321 ATr=I T 03AA 3509 HSWTA6PR 1626 AtmIJUW an~jIPr X 0:A AGC7 3322 ~AA= T AAAA= WO 00/61729 PCTIUSOOIO9721 93 Table m. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 3510 HSGATA6PR 1627 AAUUI3UUU CMN1MAG X CGAA AAGZAUMf 3323 aAZI A AA =~~ 3516 HSGATA6PR 1628 tUan3OAA CfLrAEJ.A X CA AXUtUtAA 3324 TrAAAAA.T A TriGA 3518 HS3.A6PR 1629 CUtXU= CLIMA X CMA .AIAUtJUWJ 3325 AAAAAMT T CCALAAG 3519 HSGATA6PR 1630 PACUUtf C .X37flA X CZA AAUJUE 3326 AAATATr C CAAA~ 3528 H.~AT6PR 1631 AAAA=rU CtUDAMA X CGA ACUtUtttG 3327 CAGAAAr T CAGrrr 3529 HSGATA6PR 1632 AAAAAULJU CMUXIG X O:A A~aJULt 3328 ~AAA~krI C AGTITIT 3534 HSGAA6PR 1633 AGAAAAA CtrUILG X 03AA AU[IGAC 3329 GTIAGT T TITITIC 3535 HRZAMPR 1634 AAGAAAA CUGAUA X O:A AAttLflAA 3330 TMWA=r T ITIWI 3536 HSGArA6PR 1635 AAAflAAAA CUX2MAG X CCA AAAItCflA 3331 'ICATr T ITIWII't 3537 HSGTA5PR 1636 CAAAA CMfAMflG X CXMA AAAAttU 3332 CTI'IT T 7IWIMI 3538 HSa'AAPR 1637 ACAAAAA CtLIGAM X CCA AAAAAUT 3333 AG~TITI T TICrriu 3539 HSGTA6PR 1638 CAAAA CEIGAU X OGA AAAAAAUC 3334 GUaI'T= T w'rrIGIG 3540 HSGAT6PR 1639 tCAA CX fl X CCA AAAAAAAIJ 3335 ATITTI T CrIIUIk 3541 HSGATA6PR 1640 tLXCAAA CMfAUA X 03A AAAAAAAA 3336 TrITITI C TIIMI 3543 RSGAM6PR 1641 CAUICArA CAUMxG X CA AL3AAAAAA 3337 TIrr T =%A 3544 HSGA.6PR 1642 L)IXUMC CUGAMA X C1A AAGAAAA 3338 TI'IrtI T GIM.A 3556 H9QTA6PR 1643 CCtGALP CUPLXAG X CMA AIUtUCAUU 3339 AATAAAT A TII 3558 HSGATA6PR 1644 G3C@GA CLJAM X (GA AMMIUEC 3340 TGAAAMT A rivIl= 3560 RH.AMPR 1645 U003= CtflAUtX X C3A ALUMMEIJU 3341 AAAMTAT T CGOC= 3561 HS~rPR 1646 (IGO= C GAUM X 03A AAUA=IX 3342 ?A.TaT C 7000 3582 HSGAME6R 1647 UNAA CUMXPL X C3A AIX U 3343 AG3 T ' TCI 3583 HRsGAMPR 1648 CUGAA CUGAUC; X CMA AAO= 3344 0300= T CCIrCiG 3584 HG6PR 164 AL7AA LCUAIG X~ K MA AAA= 3345 MCC= C CrriT r 3587 KH.TA6P 1650 AAAL= CMJYUQ X 03A ~AGAA 3346 GAT=1 T TCAGrrr 3588 HSGATA6PR 1651 AAAAACfl CUGAUGAG X COA AAGGAAAU 3347 A~rI=r T CAITrrT 3589 NSGAT6PR 1652 AAA UGAM Xxi K AA AAGGAA 3348 TIIT= C ArI'I7r 3593 HSG.AMPR 1653 AAGAAA CttWXW X OA A~t!AAAG 3349 CrI'i T TIrir 3594 HSCATA6PR 1654 AAG3AA CLEAMAG X CGA AALZ"A 3350 TrIGTr T TrItCI= 3595 HS.kT6PR 1655 AMM)A CUADM K a: AACGA 3351 TIZGI'I T TI~rIr 3596 HSGT6PR 1656 CAAa COGAL~t3 X CrA AAAACLX 3352 'TG T TCrri 3597 19GTA6PR 1657 GOUAAM3 CUGAUMG K CGA AAAA~aUG 3353 CAITrr T 07T= 3598 HSGATA6PR 1658 L13CAAM CUAUGxG X CA AAAAAALU 3354 AGirr C CiITIM 3601 HS.kT5PR .1659 QGMIWA CX!XM X MA A~aaAAA 3355 TITrItt T TICAA 3602 HSCAT6PR 1660 ACU~ CtUiA17= X CA AAG.AAA 3356 TrrIttr T 'iCAA' 3603 HSAT6PR 1661 C~a CU3Vw= K CA AAGGAA 3357 TI'IWI= T GCAC7 3615 HSA6PR 1662 GAGAtIE CMLP X CrA AGC 3358 ACGT= T GkBG t 3621 HSGATA6PR 1663 AGCUUGxA aIXPO=~ K CA ACUZAA 3359 CIMA~Pr C TCAA 3623 HSGAMPR 1664 tUG X7 CUX2Gl X 03A AGAUUtA 3360 IAA=~ C AAAGC7M 3630 HSGAMPR 1665 CCUrA= CLOAG K CA A~UJ 3361 TCAAAGT C ACIW 3640 HSCAMPR 1666 ACUC CUAIXM K CA ACUA 3362 CCTC2; T 00t 3649 HSCa;6PR 1667 U -7 CULML X OMA ACGUCr 3363 ~GPK T ACOO 3650 HSC.A.6PR 1668 GUU33O CUAVi X CA AA3 3364 CAGAr A ~CCO 366 HSGM6PR 1669 tXWJCT= CtflAE;G X OA A==tttf 3365 CAAGT A G~nkAA 3670 HSGAMI6PR 1670 A~ci=tE ct~xAL K OA A~a]A 3366 AM A GAM=~ WO 00/61729 PCTIUSOO/09721 94 Table IT. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 3679 HSGA1k6PR 1671 CCAZX33 CU3ALG X OakA ADUC= 3367 G(AAZIM T CCW=i 3680 HSCATA6PR 1672 GocfLr ac~XAGA x CCA AAIrAmW 3368 AAMATr C C;T 3690 HMUTApR 1673 AALMCAAA CUAMin X OMA AGCrU 369 AGTG3r C TI7Tha 3692 -HMAA6PR 16-74 AAAAAAIGAUGA X 03A AGG 3370 TGOC'r T ITI ' 3693 HSGTA6PR 1675 GAAAUM CLGAM X CGAA AAGA= 3371 G0C=r T GAiTri 3-'696 H-TAM6PR 1676 GAA AAtAc xUMA X CGAAAC 3372 cCvr'r~r A TrITwrIC 3698 HSGM6PR 1677 AUGAAGAA CUAM X 0CAA AIMCAAG 337-3 -cr'W T TMC'T 3699 H-ATA6PR 1-6-78 AALMAGA CUUU~XA x a3A AAMCAA 3374 TrIG=AT T TwrI=~ 3700 BSG~AMspR 1679 CALM CM-49nA X OA AAALACAA 375 -T1aT= T crra'i 3701 HsGAA6pR 1680 ACAUGA CUA MAGn X CMA AAAAtr- 3376 'IGTATLr C TIrd'I~r 3703 HSATAPR 1681 CACAU CUMtJAG X CMA AAAAAIA 3377 TATr=C T CIrIG 3704 HSATA6PR 1682 LICAAC CIGAUM X CMA AAGAAA 378 AMT=~r C AMIMI 3707 HS.TA6PR 1683 LMXA aC I X O:A AUGAGA 3379 TICI'IAT T GI'IAG 3710 HSGATA6PR 1684 -AInTM= CAnUiW X 03A ACAAIAA 3380 TIM.TI~r T G;LM 3715 HSMA6PR 1685 -CIAAAL CaX;nUL X CCAA ACtCAAM 3381 7GICrrGr A GA'rrCAG 3719 HIcAT5pR 1686 UtLtCt~ CGAMAGn X CM AULTWC=f 3382 cGAG~k 1 T CAGGAA 3720 HSGT.6PR 1687 AflUXttn CUGAL=c x aA AAICtUXU 3383 ~ AGO 'r T CAON 3721 HSGI7T.6PR 1688 GAUutXu CxMD= X CMA AAA=~f 3384 GAGA=r C AGAA= 3729 HSGTA6PR 1689 CACC CUGAM X CM AttU= 3385 CAGA C AGM 3739- HSMTA6PR 1690 UUXXX CL7i X CCA NALt!= 3386 GGO T 7CCA~ 3740 HSGTA6pR 1691 GUAiXn CUAUMG X 03A ACA r 3387 @AMiar T CAAAA 3741 HSGAT6PR 1692 tnjEnrnJ CiXBM X CCA AACA= 3388 AGM=i C ACAA 3747 HSGM6PR 1693 t-tMMU CLAx x X GA~A ~AULMM 3389 TIO A CAAM 3762 HG6TpR 1694 CAAU CILXUGA X CM& AGOC 3390 GA7GO T TAAL' 3763 BHGA.EpR 1695 UCAC= CLXMiM X CIPA AGOflA 3391 AGO=' T AALIM7M 3764 HSGA6PR 1696 LXrACPW an1 X aIIA AAG 3392 7MOrr A ALIGu'iA Where "X" represents stem II region of a HH ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20: 3252). The length of stem II may be !2 base-pairs.

WO 00/61729 PCT/USOO/09721 95 Table IV. Hammerhead Ribozymes to TR2-9 and TR2- 11 Orphan Receptor Genes Pos Target Sag. BZ Seq. Substrate I.D. No. , I.D. No. 9 HUMIR211 3393 GCM C CGAUGG X CGAA ACAGUCC 4172 GGGCIGr C GCGCI 14 HMCR211 3394 C033= CGAGAG X CGAA AGCGACA 4173 TGIr C GOCG 32 HUMiR211 3395 CCCtoCU CtrILG X CGAA ACtV= 4174 CGCGr C AGCA G 52 HUMIR211 3396 CCAGAUC CCLGAtlG X OAA ACCUU 4175 AAAiDG A GACAG 56 HUMr211 3397 GUMCAU CGAM3AG X CGAA AUCUAG 4176 CGGIAT C ATGGCAAC 68 HUM211 3398 ALU UC CMAUGAG X CGAA AUOG= 4177 GC.LAT A GAAGAAAT ~7 HUMR211 3399 trADLC CMAG X CGAA AUUUCUUC 4178 GAAGAAAT T GCACATCA 84 HUMIR211 3400 AAAUU COGAUGAG X CGAA AUGUGCAA 4179 TIGCACAT C AAATTATr 89 HIJiR211 3401 UUTCAALU CLAAG X CGAA AUUMAM 4180 CATCAAAT T ATIGAACA 9o HULMI211 3402 UtUCAA CTlAGG X CGAA AAUUUGAU 4181 ATCAAATr A TIGAACAA 92 HU=IR211 3403 GUUGULC CLGAm=G X CGAA AUAAUUJ3 4182 CAAATAT T GAACAACA 113 HLMMR211 3404 MU PAAC CMAMAG X CGAA AUCDLCCC 4183 GGAGAT T GITACAGA 116 HUMIR211 3405 1GCCCUGU CtAUGAG X CGAA ACAAtUl 4184 GAGTI T ACAGACA 117 HUMIR211 3406 CUCCG CCGAWAG X CGAA AACAAUCU 4185 ATIGIT A CAGAGCPG 143 HtR211 3407 ACZAAUCG CUGAMAG X QAA AUXXUf 4186 CAGAAAAT C CAGAT 149 HUfR211 3408 GCrAC CMIAUGG X CGAA ALU GAU - 4187 AtCGAT T GIGACAGC 161 HULIR211 3409 UAAU CMAMAG X CGAA AGCLU3U 4188 ACACPC T GATMAA 165 HUI211 3410 UAMUUAU CtGAUG X CGAA ACCAGG 4189 CACrIGAT C ATAATACC 168 HUMIR211 3411 U GUAU CMAmGAG X CGPA AIrULAA 4190 TIGACAT A ATACCCAA 171 HUMR211 3412 TCU=Ct CMAMAG X CGAA AUUAUGAJ 4191 AICATAAT A CCCM C 187 HUMIR211 3413 tPAWM CMALAG X CCAA ACIEU 4192 CAAG T CATICIGA 188 HLMIR211 3414 GUCAAUW CtfAUAG X CGPA AACCUU 4193 AAGCPDT C ATICIGAC 191 HUM1R211 3415 LUTX P CUGAUGG X CGAA AMA=GAC 4194 CAGrITCAT T CIGACAAA 192 HUkmi211 3416 AUUGMA CMAtrLG X CGPA AAMAACJU 4195 A~FICAT C TGACAAAT 201 HUMIR211 3417 GCCtUm CLOAtAG X CGPA AIJUGTrTA 4196 TGACAAAT C ACGA C 211 HUMMR211 3418 UtUrAG CMArEfl X CGAA AGCC G 4197 CGACCT C TACICA 213 HUM'R211 3419 GUtMAG CMAUGAG X optA AGAGG 4198 ADCICT A CI7AGC 216 HUMrR211 3420 UUtCUUG CU AG X CGPA AGUAG 4199 GCMIC C CAAGCAAA 227 HKMrR211 3421 GODAAU CLAUGAG X CAA ACUXU| 4200 MrAAG C ATIClr 230 1UMR211 3422 a rw a AmG X CAA AmU U 4201 AAAGICAT T CII= 231 HU1MI211 3423 C=3=A CUMMAG X PA AAtCQUJ 4202 AGICT C TGOCCAGG 246 -HUMrR211 3424 Co3GUO CoLAUAG X AA AMoCC 4203 GGCAAGAT T CCACICCG 247 HLIM211 3425 C lG CM ArmrG x aA AAEUtC 4204 GCAAGAT C CACICC 252 HUMrR211 3426 UULrIE CUIAtrAG X CGA AGLAAU 4205 ATICDCr C 03GAAAA 263 HEMR211 3427 GUAAGGAA CMfAtG X -CGA ACUtXIE 4206 GGAAAAGr T TICCI 264 HUMIR211 3428 UGUAAGA CUGALmAG X 0oAA AACUJUEr 4207 GAAAPGIT T TCCITCA 265 HUMR211 3429 UXflAGO CUGAAG X COA AAACUUEJ 4208 AAAAGrIT T CCITCAA 266 HUMIR211 3430 GGUAG CofMAG X CGAA AAAACUJU 4209 AAAGITIT C CITOCAc 269 HUMIR211 3431 GGAGUUGU CCGAMAG X CGA AGAAAAC 4210 GlTTICr r T ACAACIC 270 HUMR211 3432 LAGUI CUAG X O A AA03AAAA 4211 ITr~Irrr A CAACICCA 276 HUMrR211 3433 cIr3tr CMAMAG X CPA AGUUALA 4212 TraCAAC C C GA 293 HUMr211 3434 AAC~m]U CaMM G X GAA ACACC[ 4213 GCAGGI C AACIT 301 HUMIR211 3435 UAAAAAAU CUGAmUG X AA ACU3 4214 CAPwCCGr T ATITrITA WO 00/61729 PCT/USO0/09721 96 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 302 HUMR211 3436 GL=AAAA CUAGAG X CSAA AACaGUU 4215 A;CCx.~ A TTTTAC 304 IR211 3437 t=GAAA CCGAUGAG X CGA AUAACU 4216 CC=GITAT T TITACCA 305 HUMER211 3438 AA CGAGAG X C3A AAUAACG 4217 CITAT T TMC 306 hu'nR211 3439 GUM A CGlAW AG X CGAA AAAUAACU 4218 AGITATIT T TrACCCr 307 HUCR211 3440 GPGUUA CLXGAtG X CGAA AAAAUAC 4219 GITATL'IT T TACCACIC 308 HUMrR211 3441 GGI= CMAmpA3 X CGAA AAAAAUAA 4220 TATITIT T ACCALC= 309 HUMR211 3442 AG%= CGAMAG X CGAA AAAAAAUA 4221 TAMITIT A CCACImr 315 HtDMR211 3443 CGA=l CMAMAG X CGAA AatMUAA 4222 TZACCACr C CIGICIG 321 l-i1HUR211 3444 GCGACA CAGAAG X 0AA ACAGGAG 4223 CICIGAT C TGCi.A 325 hUmR211 3445 GXGtLCA CMATA X CGPA ACAGALA 4224 'IMCIGT C TOCACAA 344 HUMTR211 3446 =XI =UG CMAMAG X CGAA AGCLCAG 4225 CIGTCAGC C CTAACPGA 347 HUMfR211 3447 UUIC CrAeMfG X oAA AGAGC 4226 CPGCIC A ACGATAA 354 HUMl211 3448 1GAGAAJ CUSAMtfG X CUPA ADLCIA 4227 TAACPGAT A ATICICCA 357 HUMR211 3449 GLUUGG CMAUGAG X CGAA AUUADCUG 4228 CDCATAAT T CICCAGPC 358 HUMR211 3450 CX)M GA CMAMIAG X CGAA AAUUAUCU 4229 ATAATT C 'CLAGAC 360 HUM211 3451 UUUG= CULGALJPG X meAA AGAUUAU 4230 ATAATICT C CAGACCAA 378 HUM211 3452 AAAAACCU CGAMG X CGAA AUUWG 4231 GACCAAAT A AGGTIT 383 HLMI211 3453 AGAUCAAA CCGAG X CCAA ArUDUADJ 4232 AATAAGGI T TrIGACT 384 HUMJ211 3454 AACAA CMAmSG X CGAA AACCUUAU 4233 AAAIT T TIGAMCI 385 HUMtR211 3455 AAAGAXA CMAMAG X 3MA AAACCUUA 4234 7 TA rr T 'IGMA IT 386 HUMIl211 3456 CAAAGAUC CfGAGG X CGAA AAAACCUU 4235 AAGITI T CACrrIG 390 HUMR211 3457 UACCAAA CAUGAG X COAA AUCAAAAA 4236 TrrrIGAT C T MICCA 392 HUMmI211 3458 ALUI A CGA1xAG X 03PA AGAtrAAA 4237 TrIGAr T 'IGCGra=r 393 HUM211 3459 UACU CUGAWNmG X OAA AAGAUAA 4238 TIGMITA T GC=rA 398 HUMR211 3460 CCACAUAC CMALGAG X 0eA AmcAAAG 4239 CPIGOr A GnTAUIu 401 HKMR211 3461 UICACA CMUMeG X CC3A ACUUC 4240 TC= A 'ITG GA, 418 HUMIR211 3462 G~C[CU CAMAG X C3A AICUUM 4241 CAAAT C AmCIC 426 HU1'R211 3463 ULAUAJ CoAUmOG X meA ACG[Iro 4242 CCPG C ATLA 429 HUMTR211 3464 ImrCCAU CMAMAG X CGAA AMPCG=t 4243 GPCICAT T MGGAGCA 430 HUMR211 3465 CfOCUCCA CUMempG X CGAA AAUAC= 4244 AGICAT A IGGADCAG 440 HUKrR211 3466 UCACAAGU CUAXGAG X CWA PCCLGtC 4245 GGAGC A ACrIGIGA 444 IUMIR211 3467 Go)CAC CUrAMAG X 0eA AGWXCt 4246 CAGBAPCT T GIGAAGC 463 HUMIR211 3468 UUPIAPA CfLOAG X C3AA AtCUUM 4247 CAAMAT T TITAAAA 464 UIRfl211 3469 CooUUAAA C 1AMAG X CAA AAUCCUJ 4248 AAAGGMT T TrrpAAwG 465 HUMrR211 3470 ULJUXIPA CEAmG X CGAA AAAIICUU 4249 AlAT T TMAAAGA 466 HUR211 3471 UUCtUUUA CMAUGAG X CA AAAAUtU 4250 ATrrr T TAAAN3AA 467 HtMM211 3472 CoC UUUU CUGAmAG X CGA AAAAALCC 4251 GATITIT T AAGAAG 468 HIMrR211 3473 GCoUtX CoAsMG X 0MA AAAAAtU 4252 GATITIT A AAGALGC 479 HUMIR211 3474. UUUUUXG CtflAtG X CGA AMCUC U 4253 AGAAGCAT C CGAAAAAA 489 HUCR211 3475 AUAUCXA CoLMMG X CGPA AUUUmX= 4254 GAAAAAAT T TATA 490 HIR211 3476 AAUAUACU CUGmAeLG X CGAA AADUtX=U 4255 AAAAAATT T AGATAT 491 HLM9R211 3477 GAAlUU C AUG X CGA AAAUUUUU 4256 AAAAATrr A G TMIC 494 HUIMR211 3478 CAUGPAUAA CUGAGG X CGPA ACUAAXJ 4257 ATrGT A TICA'IG 496 HUMR211 3479 GnACAmAA CMAMPG X 0pA ALMcAAA 4258 TII A TICdIIC 498 HU211 3480 UCGACA CUGAMpG X CGAA AUAULCUA 4259 TGUAT T CItGA WO 00/61729 PCT/USOO/09721 97 Table IV. Hammerhead Ribozymes to TR2-9 and TR2- 11 Orphan Receptor Genes 199 HUDRl211 3481 CUCGACAU CUGALG X CGAA AUAAPCU 4260 PGTATATr C AGICGPG 504 HUMIR211 3482 MGAULC CUGAMfG X (rAA ACAlAAU 4261 ATICA'IGr C GA'ICA i51 HMIR211 3483 AAUCUUU CUGALMG X CGAA AUCCUCA 4262 'ILTWAT C AAPGAT 519 HUIMR211 3484 AAUAAUAC CI)GAAG X CGAA AMCOU 4263 CAAhAT T GrATTATP 522 HUMkR211 3485 AULAAUPA CMAG X CGAA ACAAUCCU 4264 A=TIr A TrATTAT 524 HUMIR211 3486 UIUUUAU CUGApG X CGAA AUACAAC 4265 GATITAT T ATIAATA 525. HUnR211 3487 CU.AAA CUAMAG X CoA AAUPCAAU 4266 ATIGIAT A Tr>ATAPG 527 HUMIR211 3488 UICULAUU CLUAmG X SAA ALALA 4267 TGrATrAT T AATADCA 528 HUMR211 3489 GmLCUUAU CnAM G X OCPA AAUAAUAC 4268 GIATIATr A ATAADCAC 531 HUMrR211 3490 GU GCU CMAWAG X CGAA ALAAUPA 4269 TITrAT A ADCAC 552 HUKM211 3491 GCPGUAUU CUGAAG X CGAA ACAG3 4270 AMIr C PATACIC 556 HUMIR211 3492 ACCUCCAG CA G X CGPA ALtACAG 4271 CIICAAT A CIGCAGP 565 HuMrn211 3493 A=C=CUGU CUGA=AG X CCAA ACCUGCAG 4272 CIGCAr T ACAGAT 566 H IMR211 3494 CArCtU CUGAMAG X QAA AACA 4273 'IGC Tr A CAGACA 576 HIMrR211 3495 AAACAA CtJALMAG X CGAA ACAUCTU 4274 AGeGIGr A TICrIT 578 HUMR211 3496 ccAAPcGC CtX3A[G X CGAA ACuC 4275 AIATa T GGTtu 583 HuMfR211 3497 UCADUCA CMAUGPG X CAA ACCAAUA 4276 TAI=GP T 'TAA'GA 584 HUMTR211 3498 UTAU=CC CEApG X CGAA A.CAAU 4277 ATIGCGIT T GGAAGA 601 HUIR211 3499 AUGC-A CUGMMOG X 03AA AGUCUWO 4278 GCAACr C 'GIICCAAT 605 HUrR211 3500 LCAUG CUGAUGG X CWA ACACuC 4279 GCICIG C CAAIGA 626 HUMMR211 3501 GAM=UPCU CUGAMAG X CGPA AMC=XU 4280 AAACCCAT T GAAGC 632 HMIR211 3502 EuimA CmAmfG X CAA ACUTAAU 4281 ATIGArG A 'ICGAGA 634 HUI=R211 3503 UUUCUCGU CUGAUGG X CGPA ADACUUCA 4282 'ITGAAT C ACGAGAAA 646 HUMr211 3504 AGUJ AA CtAUSAG X CSPA AUUXXT 4283 AGAAAAAT C TICCAACr 648 HUMR211 3505 ACAGCW3 CMAmGG X CGPA AGAUUU 4284 AAAAI T CCAPCIGI 649 Htnmr211 3506 CACAGUGE CUGAUGAG X 0AA AACAUU 4285 AAAA'II C CAACIGIG 663 HMIR211 3507 UttoJUG CMALGG X CGPA AGCOC 4286 GIoor T CAACACAA 664 HUmai211 3508 UU=mU CaWMAG X CAA AAGCC 4287 10=uc1: C AACPGAAA 677 HUMmR211 3509 COAUADA C AlG X CMA AXJUUU 4288 GAAAAAAT C TATM 679 M211 3510 UTCGAL CUGAUGG X CpA ACIAUUUU 4289 AAAAAIC= A 'IA[M AA 681 HUR211 3511 CUmaA arw G X CGAA ALUGLU 4290 AAAAT A 'IcAG 683 HzMrR211 3512 tXL7C CXAMAG X CGPA A UA 4291 AT'ICITT C CGAAA 695 HtMR211 3513 G3Uno CMAMeG X CGAA AG[ICU 4292 AAGGAmr T rAtc 696 HuIR211 3514 U033= C AmeIGG X CCA AAAGPGU 4293 AG IT C GraA 699 HUIR211 3515 UAAU c CMAMAG X CAA PGAGUJ 4294 ACCrIC3r A GCtrATIA 706 HMI211 3516 UJ wGUU CALGPG X 0AA ALM=CU 4295 TAGCAT T ACICAA 707 HEtRM211 3517 GoLC= CLGADGG X CAA AAUoCU 4296 ACCAT A AC1GCAAC 717 HUIrR211 3518 AAAPUUG CAUmGG X CGAA AGUOCAG 4297 CIGCAACr C CAACrIIT 723 HUMR211 3519 UGUUAA CUGAUGAG X CGAA AGUJGGAG 4298 CICCAACr T TIGrACA 724 HIER211 3520 CtUPtCA CMAUG X CGPA APGXU.A 4299 ITCCAACIT T 'IGrAACG 725 HUMR211 3521 UanUALC CfAM pG x CGPA AAPGUCl 4300 CCACIT T GTAACAGA 728 H1M'R211 3522 CUAULUG CUGAUGAG X QAA ACAAAADJ 4301 ACrrrIGr A ACPAAG 735 HUMTR211 3523 ACUUtAC CAMNLG X CGAA AUCUGUUA 4302 TAACACAT A GIGAAAGr 744 HUMIR211 3524 MeCCUtm CfATGf l X CGAA ACUUEXC 4303 GIGAAAGr A CA~GICA 751 HUM T211 3525 GtG=U CUAmeG X CAA AtUtUA 4304 TCA P C AAC-XrC WO 00/61729 PCT/US00/09721 98 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 763 HUMI211 3526 CLor U CUMAMAG X CGAA ACAGtCU 4305 CI~r .;ATIC; 764 hUMIR211 3527 CCUGAAUC CXAMAG X CGAA AArCA 4306 GGIGIT AZ;TICAm 768 HIR211 3528 CAUUCUl CMAMIG X Q3AA AIAACA 4307 TGITACAT 7 GAATG 769 HUZ[R211 3529 ACAUt CUGAnAG X CGAA AAUAAC 4308 GITCT C ;GGAAaW 778 iUTR21. 3530 UAUCAUGl CLUAG X (CAA ACADUCCU 4309 AGGAAT r - CMGAATA 779 K24fl2 3531 _ALAUMAU CUGAMAG X 03AA AACAUC 4310 GGAAT C A:IGATAT 786 HUMIR211 3532 UGAUGAA CMAMAG X CGAA AUMtAL 4311 TCAIGA A -C---CA 788 HI211 3533 GAUG3 CMtf AG X CGAA AAU U 4312 ATGAATAT CATCATC HU 211 3534 AGALJGAU CfLUAG X CGAA AAUAUtCA 4313 TGAATAT C ;CcIr 792 HUMIR211 3535 CCAGAULG CMIAMAG X CGAA AMAAUAU 4314 ATATICAT C Z;tCtWA 796 HUME211 3536 UUACU CMAMPG X CGAA AUGGAMA 4315 TCATA C -GGrA 803 HU4211 3537 UrAGUUUU CLAMAG X MA ACtAGA 4316 TCIpGS A ; 814 HMR211 3538 GCACAmU CtLAmG X G3A ACM GUU 4317 AACIGAGr C .20CIIG 832 u mH 3539 CCu.AUCU CCGAG X CGAA AGMCAUC 4318 GATGACAT C ;CATAG 837 HUDm211 3540 UUCAGCCU CAUAAG X CGAA AUGAML 4319 CATGAT A XGXCIGPA 847 HUMR211 3541 CCtLACAU CmAmG X CGAA ADUCAGC 4320 GCIGAAT C ;--GICa 852 HUZMR211 3542 AM .CU C=AG X C3AA AC1AUU 4321 AATCA r C;a AT 861 HUMMR211 3543 tUCUtA CUGAM4G X CGAA ALUUCCC 4322 AGSAT C:~2AGrCA 862 HuN211 3544 AULCU CMAMAG X CGAA AMCC 4323 GCGAT T ;GrCA 863 HUml211 3545 AAUA= CUtAx AG X CGAA AAALLa 4324 pAQTIT A ;GrACATr 867 HIMrR211 3546 GGCCAAUfG CUAAG X CGAA ACUAAAU 4325 AITAAGr A CT=uu.. 871 HUMI211 3547 CPUUa CUGAGG X CGAA ALUM=CU 4326 AAGCAT T 3CCAATG 884 UE211 3548 AALGAfU CMAmGG X CGAA AmLCAUJ 4327 AAGIUG= T ;CACATr 885 HimmR211 3549 UAAUGAUG CGALGAG X CGAA AACCACAU 4328 AIGIT A CATCAA 889 HUirR211 3550 LMCUAAU CUGAUmPG X aAA AIUAACC 4329 GGrrACAT C A-TrpcG 892 UMIR211 3551 GAU=tU CDnAUGI X C3AA AUAUA 4330 TACAC T ;CAC 893 HUMIR211 3552 AGAUUtC CUGAGAG X CGAA AAUGAUGJ 4331 ACAT A GAC 900 HUMR211 3553 UUUCCAA CUfA1pG X CUA AUC=A 4332 TAGCGAAT C -TGGAAA 902 HUMIR211 3554 GUUUUUC CLALAG X CGPA AGAUGC 4333 GGAA=T T 33AAAAAC 912 HUMMR211 3555 AAGAUCDJU CMAUGG X C-AA AGUU0C 4334 GAAAACr A ACtAtTr 918 HUMrR211 3556 UIGAAA cUGAmAG X CPA ALUXAG 4335 CIMAGAT C TIICAA 920 HUMiR211 3557 tUDGNGA CUGAUGAG X CGAA AGAU U 4336 AAAGATCT T TCICAAA 921 HUMLI211 3558 ALUuGAG CMGAUGAG X CGAA AAGAUCUU 4337 AAGAr T CICAAAAT 922 HUIR211 3559 UADUDDGA CUIAMAG X CGAA AAAGAU 4338 AGAM=IT C TCAAAAM 924 HUMIR211 3560 ACUAUtU CUGAMAG X COAA AGAAAGAU 4339 A7CITI C AAAAT 930 HUIRM211 3561 UCAUULAC CLUAIG X CGAA AUUJUClG 4340 CICAAAAT A GrA.AA 933 HMIR211 3562 CAUnCAU CLAmAG X CCA ACUAUtU 4341 AAAA A ;.IGAAAG 943 HuMIR211 3563 CAAULA CMAGG X CGPA ACAUUrA 4342 TGAAATIr C T-AGAIG 945 HUMR211 3564 urAAtrA cLIMAG X CGPA AAIX U 4343 AAATGICT A -rCATIGAA 950 HUMrR211 3565 AmGCEUrC CUGALAG X CAA AUCADPCA 4344 TCIGA T GAA=r 958 HUMIR211 3566 CAU=UU CGAUGAG X CGAA AGCUWCA 4345 TGAAAGCr T NIGCAA 959 HUMrR211 3567 UrAUCU CtUAmGAG X 0eA AAGCUUC 4346 GAAIr A ;GCAATGA 972 HUMI211 3568 CAAAGAG COLAIAG x CA AIrm U 4347 AAGT A CCICITIG 976 HUM211 3569 aCACAAA CoAmG X CAA AGGtr 4348 TGATAC C TIMu= 978 HEM211 3570 UUCACACA CfLAEG X CGAA AG IAU= 4349 ATL T TGIGIGPA WO 00/61729 PCT/US00/09721 99 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-1 1 Orphan Receptor Genes 979 HMIR211 3571 ALIrACAC CUGAUGAG X CCAA AAGAGGA 4350 T ACCIT T GIGGAAT 988 HUMR211 3572 UJCUtA CUGAUGG X CGAA AUIACAC 4351 GMIuGAAT T CAGAAA 989 HUrR211 3573 ALUJU CMAmpDG X CAA AAtUrACA 4352 TGIGAATT T CAWAAAT 990 HIZ211 3574 CAUUU CnAmAG X SAA AAAUUCAC 4353 GIGAATIT C AAGAAAG 1016 HUE R211 3575 CCUUGA CtAUG X CAA ACALC 4354 CGIGA=T T TCApA 1017 HDUtR211 3576 CCCUUG CMAGG X CGAA AACAUCAC 4355 GIGAIT T CAA03rA 1018 HUKM211 3577 AI3rUU CALUGAG X CGAA AAACACA 4356 TGATT C AAG3GCAT 1027 HUMMR211 3578 GAGUGCA CMAMAG X opA AECCUUJ 4357 AGGCAT T TGACACIC 1028 HuMvR211 3579 AGAG CMAMPG X CGAA AAU3CJ 4358 AGC3AT T GACICT 1035 HUmlR211 3580 TUtCAA CMAMAG X 03AA AGUCAA 4359 TIGACACT C TItAAAA 1037 HUMMR211 3581 GCUUUtC CtAmSAG X CAA AGAGo= 4360 GACACICT T GCAAAAGC_ 1048 HUNMf211 3582 C.GAUUC CUGAUGG X CpA AUGCUWU 4361 AAAXGCAT T GAATCCIG 1053 HUmrR211 3583 CrUCLAG CtnALpLG X CGAA AUUCAAM 4362 CATIGAAT C CIMAG 1081 HUmi211 3584 CCOCUACU CUAG X CGPA AGCtU= 4363 CCAGAG C PGI'M= 1085 HUMIR211 3585 AMmC CMAWAG X CGAA ACoWoU 4364 AGCTCAGT A G0CG2CAT 1106 HUMIR211 3586 ALUM=G CrAWAG X CGAA ACACUJ 4365 (AAGI T A CACCIMT 1112 HULM211 3587 CCAGAJ CMAUCAG X CAA AfalPC 4366 GIACACCr A ATCCI 1115 HIMrR211 3588 LUCCAX CMAUGAG X CGAA AUEKHD 4367 CACCIAAT C AC GA 1125 HUMR211 3589 tU3Cuu CMAMXG X CAA AUCCCAG 4368 CIG.T T CAATA 1126. HuMI211 3590 MIAmU CLAUGAG X CGAA AAtUCCA 4369 ToCGATT C AGCATAA 1133 HUMMR211 3591 CfGLJU CtLAmelG X GA AL1tCUUA 4370 TCAAGCAT A AATIkCAC 1137 HUMR211 3592 UtGoU CtAmLrG X CGAA AUUUAUOC 4371 GCAAAT T ACXoGMA 1138 HUMIR211 3593 ULtxXH CUGAUGA X CIA AAXJPM 4372 CATAAATT A CACCGAPA 1160 HUMI211 3594 UtL3GG CMlAtG X CGAA AGGC 4373 GC0CT T CICAGA 1161 HUMR=211 3595 ALCxA CUlMAtrLG X CGA AAGmCC 4374 GGCCCIT C TCAGAT 1163 HuDM211 3596 GACGC CLAMAG X CGPA AGAAG3G 4375 CCICT C ATIC 1170 HuM211 3597 L A.flfD CUCAmLIG X CA AL3COGA 4376 TCAGC T CACAGI 1171 HUMR211 3598 CUACALUJ CUGAUlG X oA AAtGC= 4377 CAGT C ACAT G 1178 HUM211 3599 CGAAAGC CUGAMAG X CGAA ACALMA 4378 'CACIr A GrrIC 1182 HLMIR211 3600 GAGCCt A CUAG X CA AGCUACAU 4379 AGIM T TCAGI 1183 Hun211 3601 UGAGC= CUGnrIG X 0PA AAGCUAC 4380 TGICr T CeA3I 1184 HUMIR211 3602 GUCAGCC CUGAmGG X opA AAAGCPC 4381 GIkGr C AG.=cA 1190 HUMIR211 3603 G3AUJ CUAG X oMA AGCCoGAA 4382 TICAmer C ACCAr 1200 HUMIR211 3604 CAtPmeG CMArEf G X CGAA AG3CAt 4383 CCATl r T CI0CIAG 1201 HUMrR211 3605 GCAItrA CMAtG X CGA AaAGfL 4384 CATOCIT C IC1T 1203 HUR211 3606 AmCAUAG CtLAtLG X CGA AGAAGGCA 4385 TGCICT C CIMTr 1206 HUM211 3607 CUCAGC CInOrG X CAA Am3AAG 4386 CrI or A TGCMIGG 1216 HUMIR211 3608 CALXtAM CMAtr G X CGAA ACUt0 4387 GCCIGAGr A CCIGAAG 1231 HUMIR211 3609 CCCCAAU CUAtrnG X 0pA AGECPCA 4388 TGICC A CATI 1235 HMIR211 3610 GACtIIC CGtrLMG X CAA AIMJAG 4389 CA~ICAT T G33IC 1243 HUm211 3611 UCGAG3CA CfLAtrG X CAA ACCtA 4390 TGGGGAGr C TGCCIA 1249 HUMZ=211 3612 GCAGUW CUGAtrlG X CGAA AmCPApC 4391 G1ItIu. C CAGCIG 1261 HIR211 3613 UtnADPG CLAmGG X CG!A ACPDGJ 4392 ACIGIGEr T CIAA 1262 HUMlR211 3614 AIDAUA aAtlG x CEA AACkDC 4393 CICTGIT C TIATCAAT 1264 HULMI211 3615 GCAUWAU CMAmpG X OAA AGAACArC 4394 GCTrICT T ATCAAG WO 00/61729 PCT/USOO/09721 100 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 1265 I-ItrR211 3616 UOCAUUGA CGALMbG X CGAA AACAACAG 4395 CIGTrr A TCAA= 1267 HUM211 3617 AGAUU CUGAGAG X OAA AUAAGAAC 4396 GrITTAT c AATGCr 1283 HUMR211 3618 G3AAUCGA CUGAUGAG X CXAA AGUCCA 4397 'TIMACT T 'IiTC C' 1284 HUM211 3619 AMLAALtG CUGAUGAG X CAA AAGUTC 4398 GOCAT T CGATIer 1285 HUIM211 3620 AAGGAUC CUGAG X Q3AA AAAGGC 4399 GGCAE C GATICTT 1289 HUMIR211 3621 AAAGAAGG CUGAUGAG X CGAA ALCGAAAG 4400 CIrICGAT- T CCTICrrr 1290 HtMbR211 3622 GAAAGAAG CtAULAG X CGAA AALTGAAA 4401 TrICGATT C crirc 1293 HUMRl211 3623 CtG3AAAG CMAUSAG X CGAA AAAtLG 4402 CGATIUT T CrICCAG 1294 HUMIR211 3624 CCUMAAA COGAMAG X CGAA AAAAIC 4403 GATICCIT .C TrIC= 1296 HUM211 3625 AGCUGGA CtLrALrAG X Q3AA AGAAD3AA 4404 TICCtIC= T ICCA=T 1297 HUMrR211 3626 GAGCCUGG CMAMOG X CGAA AAGAAGGA 4405 'TCICTr T CCAGIC 1298 HUT211 3627 AGAGCCG CUGAMAG X 03AA AAAGAAPG 4406 CCTIrrr C CACICT 1305 HUIMR211 3628 UtCCCUA CXAMAG X 0AA AGCLM 4407 'CCDG C TAMGCAA 1307 HUYMR211 3629 LUUG CUCAAG X CGAA AGAGCtf 4408 CAGGICT A G33CAAGA 1325 HUqrM211 3630 ACCAGUGA CUGAG X CGAA AUCUGUU 4409 AACAGCAT A 'ICAC r 1327 HUMrR211 3631 UCCAGJ CUAMAG X CGAA AUAtmf 4410 CAGCATAT C ALauiIA 1341 HUIMR211 3632 ALCG CMAMAG X CGAA AGCUTrA 4411 IGAAAGCr T ACIOAAT 1342 HUMmR211 3633 CAUC CUGAUGPG X CGAA AAGCEUC ' 4412 GAAAG= A CIGAATG 1355 HUMR211 3634 AGAGUAA CUGAUGAG X CGAA AGJrCAUU 4413 AATGAACT T TrrAC 1356 HtMIR211 3635 AAGAGUAA CGALAG X CGAA AAGUUCAJ 4414 ATGAACIT T TrpcIrr 1357 HUMrR211 3636 CAAGNGA CAmG X CGAA AAAGXUA 4415 TGAArrr T TMCItIG 1358 HfLR211 3637 CCAAGAGJ CUGAUAG X CGAA AAAAGUUC 4416 GAACI'iTr T ACICIGG 1359 HUI211 3638 ACCAAGAG CMAG X CGA AAAAAGUU 4417 AACITIT A Clunr= 1362 HUMMR211 3639 AAGCAA CMAG X 0AA AGUAAAA 4418 TITrr'Cr C TI0ICTT 1364 HUMrR211 3640 GCAAGC CUGAmOG X CGAA PAGAAA 4419 TMrCICT T usICna. 1368 HUMIR211 3641 CUGGCAA CUGAMAG X oSA ACCAAGAG 4420 CICTIGr C TI..AG 1370 HLUM211 3642 CACo3C CUGAUGAG X CGAA AGADCAAG 4421 CIOtC T GCTAIG 1397 HUMl211 3643 AUAGUtC CfAU AG X CGAA ACAUTAU 4422 A'IGAAGT A GCAerAT 1404 HUtR211 3644 tGCuAUA CUCIfmeG X CGAA AGUU 4423 TAGCAAcr A TATIADCA 1406 HU211 3645 GU1CUAA CmAmG X 0pA AUG=E 4424 GCAAT A TNGCAAC 1408 HUMrR211 3646 AUCLX U CUGAUGAG X CGAA AUAGG= 4425 AACTAT T AGCAACAT 1409 HULMI211 3647 AA0UTC CUGAm2G X CGPA AAUAUpM 4426 ACTAT A TAACATT 1417 HUMI211 3648 AAUtACA CUGAmG X CaPA ALM=C 4427 AGCAACAT T TGICAATr 1418 H'MR211 3649 CAlmUeC CMA GW X CGPA AAUlEZXf 4428 GCAACAT T GICATIG 1421 HUM 211 3650 AGACAAUU CUGAmGAG X CA ACAAAtX3U 4429 ACATrIUr C AATIGICT 1425 HUMr211 3651 GIAAGAC CMAmGG X CGAA ADGCAA 4430 TIGICAAT T GICrICAC 1428 HUMI211 3652 AMIGMAA CLAUGAG X CGAA ACAA1XA 4431 TCAATIGT C TICWCAAT 1430 HUM1R211 3653 CLMUn COUGAG X CG3A AGACAAUU 4432 AATIGICT T CACAATAG 1431 HUMIR211 3654 ACUAfUJ CLMAmeG X CGAA AAGACAAU 4433 ATIGIT C ACAAT 1437 HUMMR211 3655 UtAAGAC CLArWG X CGA AUMA 4434 TICAAT A GICTICAA 1440 HUMIR211 3656 UUGAA C AIJY CGAA AUMU 4435 ACAATG C TICAACAA 1442 H=fl211 3657 tI0itn CAPa X CGAA AGACUADU 4436 AATIl= T CAACAAGA 1443 HM i211 3658 ALMu=u CUSAMAG X CGAA AAGACUAU 4437 ATICIT C AACAAGAT 1452 HUM1R211 3659 LrcADU CUGAmG X CGPA A10U0f0 4438 AACAAGAT A AAAGICA 1459 HUMIR211 3660 unCTjuU CfAmrGx X CGA AUUUuA 4439 TAAAA=G C APCAGAAA WO 00/61729 PCTIUSOO/09721 101 Table IV. Hanumerhead Ribozymes to TR2-9 and TR2- 11 Orphan Receptor Genes S1477 PU-21l 3661 1cr~ am pr xtlt~ XGA ~tA Nu-u= 4440 ?~AAWAT T :kIGCA= 14-08 hUL .211 3662 =AMAlA GfLrAfLr3A X CAA AAUUULU 4441 PGAAAA~r A TIA 1480 HE 9211 3663 G1CU CUGAMAG X CGAA ALMAUUU 4442 AAAAT=.. T C-TA 1493 MUHR211 3664 ~AJGLrAA CMAMPG~ X CGAA AE~LX; 4443 GAGCACAT C TrCAAALT 1495 Hu2ER2l11 3665 GU= CflAUGM X CGAA AGAUlfl 4444 G2CA= T CAACLAC 1496 uZER2 11 3666 UGUNGUUJE CflALUG X CGAA AAI33J 4445 CA~CArr C A~AMC 1502 HUm211 3667 ACLX)tf CtXAMAG~L X CMA AGUtSA 4446 TICAAACr A CAM=I 1510 HL-MR2 11 3668 tflXFCAA CMfAMWP~ X CGA .ACLL=~U 4447 ACGG~ T TIGTAACA 1511 Ht2UlR11 3669 CUMUECA CMAUGAGL X CflAA AACUCW 4448 CGGAT T WG'ZPCaz 1512 HUtqfll 3670 GtflJLFC CAMPG X 03AA AAACED 4449 AGITT T GAC= 1515 HUR.211 3671 CAtUG= fLrAU3--A X 03AA ACAAAACEJ 4450 PIII= A ACG= 1526 Ht2{R911 3672 c~GJUU mrxrAtA X C cAA ACCALIaE 4451 ~AM3= T AAA=CI 1527 hUT211 3673 GCCA CMALXJ1AL X CG1AA AACAIfl 4452 GCMI* A AACI=I 1532 ll Mil21 3674 LMAALMA CXMILtEQ X CX3AA AtUtUAAC 4453 GIAAACI' C TGATG 1538 HtJ!mfl 3675 UAULtAUC CtXAfLr-P X CGF.A AL7321GfG 4454 CICIGCAT T CAGS 1546 HrI-Rf211 3676 CAUA=EX Ctfl1MAl X CGTAA ALMA2 4455 CAGC-AT A CGAATAM~ 1552 FULIR211 3677 GG2A CMfALUG X 03A AUtt-IA 4456 ATANCG-AA A IMIP 1558 Ht-t1iR211 3678 CCUEM7AO CMtATflA X CGAA AG3CALWJ 4457 AMT= A CCI=AP1 1571 KzME~11 3679 %AAGA fLrAUX~ 03AA AUEGX 4458 AT~LflAAT A GBCItIT 1574 HIJzfIM11 3680 aflAKA CflALAL X OAA ACUAUIXfl 4459 GCAAG A CLMPIC 1577 9.1-M.~211 3681 M~AMMA CEXAIflG X 03PA AGUCUNJ 4460 ATG= C TCI 1579 HUMIR211 3682 Ct73GPCUG CUAfl X OSA ACIALIMM 4461 AM =i~ T CG=t 1580 HII211 3683 tL~LjjUA CfLCAtLr. X C aA AGP 4462 Gm~ciC c A1tcmrm 1584 HU1'rM~11 3684 AM.lA=lf C~AnUin X 0AA ACWG 4463 ITIr c ac.LA=I. 1590 HtINM~11 3685 Gaxw-u cuomrw~ x cGA AuaxEx~c 4464 GICAGA C AECCAAGC 1593 Ki!'fl 3686 tIXI3U OCtflPL X 03A AMfA=Ef 4465 CAL3GIC= C CAG= 1601 Ht2DERl211 3687 AM =xx =.GAG~ X MMA AGM=~ 4466 CA=r A GAAAM 1619 HE2IfIR211 3688 AAI3E= E Ml1IG X 03A AUtAGOLI 4467 CGAC=GA A GAAA= 1627 HE~LZ 211 3689 UtXCtttXA CMfAMNAG X 03AA AUL= 4468 PAGAAA T 'ICA0AAA 1628 HUM211 3690 UtIttUL= CfLUCEA X 0: AAJtIt= 4469 GAAAAT T CAGSAAAA 1629 HUKEM11 3691 CIUULtt CMAMAG X CGA AAAXUL 4470 AGAATrr C A9GIAAPG 1641 MuKM~11 3692 UUtrCXM CMfAtGAG X 03A APCUXX 4471 AAAGG~ T ;aGIGCA 1642 HZEtF.11 3693 A1XCCA CtLr-4WG X 0A~A AAGC=J 4472 AA1II' A IUTG70AAT 1651 HE~r211 3694 AAtLr= CUGAInAG X 03A AMJEACA .4473 TGIGGAM T CCa)A.T 1652 HuEnM11 3695 tm = axw G X oA AALXLCC 4474 G1X1T C OW.A 1659 HLIIMl211 3696 GGUEPI.WJ CUflAtL X C A ALMMAl 4475 ItAAT T AMACC 1660 HMMn~11 3697 U33UUAUA aflAMA X OA AALLUJOG 4476 CCAAGA=' A MAACC 1662 HJUflR211 3698 Lujom . fAtLrA x o3A ALAALUEJ 4477 AAGAlA A MACA 1664 HLIM211 3699 G~uutmu aXnAtr X CMA AIUflA=1 4478 CAn A ACCAAAAC 1675 HU1R211 3700 CALLMOG CUAUG; X CMA AM=lJU 4479 CAAAAT A ITCtP-A 1677 K2IR21 3701 GIUtA= CtrAfLrP X C GA AIJ~LMD= 4480 AAACAMiT C C~AGAT 1690 HtM211 3702 AUAA)CUG CUAnUIn X CSA PGOlGUA 4481 TGALtr A CW=d 1696 HU~'fl211 3703 GMJ=A O!IAIG K C &A ACUA 4482 Cr-AGG T 1697 HUM'l211 3704 AGL~xM CfLrAt~i K a~A AcatUM 4483 TACA= A 'T CL' 1699 HLIMn~11 3705 GAG=u c~IflrL K cia xLw . 4484 CAG3LIG . C CGAMC WO 00/61729 PCT/USOO/09721 102 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 1706 HU14IR211 3706 | CoUAG CCM AG X CGA AGCCDTA 4485 'CuCAT A CICICAG 1709 -U11R211 3707 AMDC=GG ColDGG X CGAA AGLU 4486 AGMCiTc A CCA 1712 HUMrR211 3708 GCAALUCU CtGAmAG X oGA AGUAGUAG 4487 CnACT C GATIC 1717 HUMTR211 3709 AxM 3C CGAGAG X CGAA -AuCUGpG 4488 ACICAGAT T GC ZTT 1725 HUMIR211 3710 CGUCUA CMAMAG X oAA AGCLX3A 4489 'IGCCAGC T TAGIG 1726 HUMR211 3711 UCLAGU CXAmG X CGAA APCI=C 4490 GAGIT T AACIGA 1727 HUMR211 3712 AUCAGC CrAmG X opA AAGCXG 4491 CCAGCIT A ACIGAT 1743 HUMRI211 3713 PGmpDGG CUGATAG X OAA AGCAULCA 4492 'TGAAICT A CCACACr 1748 HLUM211 3714 tUUCAGj CfrALG X CGAA ?AIGM 4493 GCIMLAT C ACIGAA 1759 HUM211 3715 UGPAAAAC CMAG X CGAA LCTA 4494 TGAPGAAT T CITITICA 1762 HUMR211 3716 CUUUGAAA CUGAM3 X CGAA ACAAIUCU 4495 PGAATIWr T TrICAAG 1763 HUMTR211 3717 CCtUUflAA CtIAAG X CGAA AACAAUTL , 4496 GPATIGIT T TICAAAG 1764 HU-1R211 3718 ACCUUtA CUSAMMG X CGAA AAADWJ 4497 ATIGITII' T WAAA 1765 HUMIR211 3719 GACCUUmL CCGAGG X CGA AAAACAAU 4498 ATIGITIT T CAAIC 1766 HUMIR211 3720 AGACUUJ CLAA X COA PAAAACAA 4499 TIGITITT C AAAGGI 1773 HUVM211 3721 GCCAATA CrA.G X CGAA ACCUUMA 4500 'CAA=1r C ATI 1775 HUIrR211 3722 UooAAIJ CLAWAG X CGAA AGCCUU 4501 AAAmICT C ATIGOCA 1778 HtMMR211 3723 AAPIJE CWnA G X CGAA AMAGAC 4502 G3ICIAT T GCAAT 1785 HULM211 3724 ALMCGUA CSAUGAG X CGAA AUUGtAA 4503 TIGCA.AT A T;a Tr 1787 HuM1R211 3725 UCAAULC CUGAmfG X meA AMAU[CC 4504 GCAATAT A CGAATIGA 1793 HUR211 3726 ACCUGUC CtXDGAUAG X 0A3 AUUMAU 4505 ATACGAAT T GPCOGIGT 1802 u-MR211 3727 UGUO33AU CtLAULAG X CGAA ACACU 4506 GACAGILr T ATCACA 1803 HUMTR211 3728 AUUCEA CCGALUG X CGAA AACACtU 4507 AMG=Irr A 'TCCCAT 1805 UM211 3729 AUAWLtM CUGAmAG X CCAA ALACACU 4508 AGI=AT C CCACAT 1812 HUMM211 3730 UUECAAAA CUGMG X CMA ADGoGGA 4509 TCCCCAT A TITIAAA 1814 HUMTR211 3731 AuUTPAA CtArumG x 03AA AUm=m 4510 .CCAC T TIGAAAAT 1815 HUMTR211 3732 CAUXXXA CTLAMAG X AA AAUAlMf 4511 CACAT T 'IGAAAAG 1816 HUMI211 3733 CCAUUUC CtnSAMG X CoA AAUAUG 4512 ACATIT T GAAAA'I3 1836 HUM211 3734 AGAGUUAU CoLAM G X CGAA ATLCPG 4513 CImG T ATACICT 1837 HUMB211 3735 GAGAGUA CALG X CGAA AAIEUE3A 4514 'ICATT A TAACICIC 1839 HuMrR211 3736 UuGmGj ClAmuG X CA AUAAI L 4515 CAGAA A ACIC=IA 1843 HUM211 3737 txPLxA CLMALUAG X CGAA AGUEPIA 4516 TATACT C TCAAATA 1845 HUMIB211 3738 AAmxPDU CmmAxG X C:AA AC40-UW 4517 ATAPCICT C AAATAAT 1850 HUMtR211 3739 teCCAU CUGpoAG X 0AA AEUMfA 4518 'IIAAAT A ATITICA 1853 HME211 3740 CTfOLmC CMAMNAG X CGPA AUUAUUM 4519 CAAAA T GGICACG 1857 HUM211 3741 AALroU CoAoA X 0:pA PotAUUA 4520 TAATII C ACAGC 1865 HIMfR211 3742 AGUMtA CUSAofG X CGAA AW13aM 4521 CACAG T 'IGAAACT 1866 HUR211 3743 CPGUUUUT CUGApG X 0oAA AMrU 4522 ACAGCATT T GAAACIG 1890 HuMIR211 3744 G UUOM CorA3PG X A ACAGrC.U 4523 AGIGIGT' A AACITPAC 1895 HU R211 3745 AACAGUUJ CUeMMG X CGAA AGoUPA 4524 'IrAAACr T AIIIC 1896 HUMR211 3746 ACAGU CtflAXPG X CGA AAGUUUC 4525 GIA=CIT A ACIGI'CT 1902 HUR211 3747 t3CAAAG CMAMG X CXpA ACAGoLA 4526 TTAACIGT T CITTCA 1903 HUM211 3748 CtrmCAAA CmEAUCG X CAA APCAGUA 4527 MCIGIT C TIC= 1905 HUMR211 3749 UTrA CLrDGAG X CGAA ACAACG 4528 ACIG=Ir T 'OAGAA 1906 HIUfR211 3750 GJrLM CGAUG X CGAA AAKAACAG 4529 CIGIICIT T GCCAAAC WO 00/61729 PCT/USOO/09721 1 03 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-1 I Orphan Receptor Genes 1929 -LirR211 3751 GGAUC CMAMG X C=-A AIJUU= 4530 CACCAAAT T C(!C1 C 1935 H-MR211 3752 AAACAGU CEAmG X CrZA AGUCtAAU 4531 ATlG=Ac C ;LCrIG'r 1942 MMR211 3753 GCUAA CLGADG1G X CGAA AGCAGUA 4532 'ICCI ' T TTIGPGCA 1943 HLmIR211 3754 ADGCUCA CSAUGAG X CGAA AGCAGLf 4533 CACI=IT T 'ITC-AT 1944 HUNMR211 3755 GAUGCCC CUGAmXG X CGAA AAGCAGU 4534 ACIGIT1 T GAGGCA'C 1952 HMIM211 3756 AAUUUCCA CtADGAG X CGAA AMCC=CA 4535 'IGPGAT C 'IGGAAAT 1960 hrRm211 3757 AAAGUAAA CUGA=A X 03AA AULAG 4536 CITAAAT T TrrACrIr 1961 HUMrR211 3758 UAAAGUAA CUGAWAG X CGAA AAU=A 4537 'GAAATr T TACrTA 1962 HUMI211 3759 UUAAADUA CUAMAG X CGAA AAADUUtC 4538 SAAATrr T TACIITAA 1963 HUMIR211 3760 UUZAAWG CMAEhG X CGAA AAAAUUUC 4539 GAAATrrr T ACMrrAAA 1964 IRf211 3761 UUUUAAAG CMAMAG X CGAA AAAAAUUU 4540 AAATITIr A CITTAAAA 1967 HLMI211 3762 ACUUUUUA CMALUAG X CGPA AGUAAAAA 4541 ITrITAC T T1-AAAAAGr 1968 HUMIR211 3763 UACUUUUU CUGMGAG X CGeA AAGUAAAA 4542 Trr= T AAAAAGIA 1969 HLMMR211 3764 UUACUUUU CMAG X CSAA AAAGUAAA 4543 TITCrIT A AAAGAA 1976 HUMtIR211 3765 AUUC=GU CMAMPG X CGAA ACUUUUA 4544 TAAAGr A ACCA 1985 HUE211 3766 AUACC=UG CMAUGAG X CGAA ADUCUGGU 4545 ACAGAT C CAAT 1992 HUMMR211 3767 AAUAAAAA COGAUGAG X CGAA ACCLUG 4546 'ICCAAr A TrrITAT= 1994 HZMR211 3768 AAAAUAAA CUGAUGAG X CGA AUACCfl 4547 CAGIAT T TITAI'IT 1995 HuMI211 3769 UAAAAUAA CtGAUGAG X CGPA AALACOU 4548 AAITT T TrPATTA 1996 HU211 3770 CUAAAAUA CMALMG X CG-AA AAAUACTtU 4549 AM =ATIT T TATTITAG 1997 HUMIR211 3771 GCAAAU C nAUGAG X CGAA AAAAUACC 4550 GGIATr T ATITrDC 1998 HUMIR211 3772 AGCUAAAA CfLr4VlAG X CGAA AAAAAUAC 4551 GITITT A TIT G 2000 HDMIR211 3773 GAAGCLAA CMAIrAG X CrAA AUMAAAAU 4552 ATrIrA T T]pCTIC 2001 HD1rR211 3774 GGAAGCUA CMAMAG X CSAA AAUAAAAA 4553 TrITIATr T TAGrIC 2002 HUMrR211 3775 GCACU CUGAMAG X CGPA AAAUAAAA 4554 TIT7TT T AGC1r C 2003 HMIR211 3776 AGOAAGC CUGAmGG X CGPA AAAAUAAA 4555 TITATIT A GCritC 2007 HtIsR211 3777 CUUAA3 CLrAmG X COAA AGCUAAA 4556 TITIA T CCCrAAG 2008 HLUM211 3778 UCUUAAGO CUGAMAG X oPA AAGUAAA 4557 TrrIr C CTrG 2012 HU2IR211 3779 AAAUTU CSADGAG X CGPA AGG&PKC 4558 u.IIor T APGAATrr 2013 HUM211 3780 AAAAUtCU c.AG X CGA APAAAG 4559 CrirMrr A AAITT 2019 HUMIR211 3781 ACUUCAAA CUGAmAG X CGAA AMUUt AA 4560 TIAAGAAT T TrIGAAM1 2020 HIR211 3782 CACLXTAA CoCAMAG X CGAA AAU A 4561 TAGT T TIGAGIt 2021 HM I211 3783 UCACUT A CUGAmG X opA AAAUJU 4562 ArATIT T 'GAAGIGA 2022 HUMIR211 3784 G UT= C WAmG X C AA AAAAUL 4563 AGATITT T GAAGIGAC 2049 HIKR211 3785 AUAUGUU G X GAWG XCKAA AULmar 4564 GCPAAAT T AAAGAAT 2050 HUMIR211 3786 AAUU CoAIrG X MA AAUtUXLG 4565 CAGAAATr A AApIGAAT 2058 HDMMR211 3787 GAAAA CnAMirG X o3A AMUTA=U 4566 AAMGAAT T TrIC=ri 2059 HUMIR211 3788 AGPAGAA CUfAUGAG X C A AAUoAUJ 4567 AMGAATr T TICItr 2060 HUMIR211 3789 CAGGAAGA CUGALG X 0AA AAUAU 4568 AGAATrr T wiwimi 2061 HUMrR211 3790 UCAmAAG CtGAMAG X CGA AAAAUTA 4569 'IGAATI T CTiM7i 2062 HU=R211 3791 AUCeGAA CUGADGAG X CAA AAAAAUiC 4570 GAATITT C TICCIGAT 2064 HOMIR211 3792 GAAIXXG CMAUGAG X CGAA AGAAAAAU 4571 ATIITItT T CIGATIC 2065 HDMR'211 3793 GGAAUCAG CtLALG X CGA AAGAAAAA 4572 TITIIIT C CIGATICC 2071 HD1R211 3794 UUUAArGG C DG x CGPA AUnXMA 4573 TIIGA T CTrMAA 2072 HZM211 3795 AUmUAAtG CtGAumG X A AA AA 4574 'TccIGATr C CIrrrAAT WO 00/61729 PCT/USO0/09721 1 04 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 2075 HUIR211 3796 ULAUUUA CUGALGAG X CGAA fTAAL7A 4575 TGATICr T TAAAGAA 2076 HUMIR211 3797 ADUCAM CIAG X CGAA AAGAAJ 4576 GATICCI T AAATCAT 2077 HUMIR211 3798 U.AUUCAU CCGALr2GAG X CGAA AAJAAU 4577 ATIMIT A AATGAATA 2085 HUMIR211 3799 GUUUCA CUGAGAG X CGAA AUUCAUUU 4578 AAATGAAT A TGAAACAC 2095 HUM1R211 3800 UPAAUU CtGAUGG X CGAA AGUGUUC 4579 GAAACACr A CAAATIT 2101 HUMIR211 3801 CAAGAAUA CMAMAG X CGAA. AUUKUaG 4580 CTACAAAT T TATICTIG 2102 HUMT211 3802 CCAAGAAJ CUGAUGAG X GAA AAUG.A 4581 TCAAATT T ATICII 2103 HUZrR211 3803 ?CCAAGAA CMADGAG X 0AA AAADUUGU 4582 ACAAATIT A TICIrI 2105 HUMIR211 3804 UCACCAAG CUGADGG X CGAA D]AAAULU 4583 AAATITAT T CTIGGIGA 2106 HUM[R211 3805 UrAECAA CMAmlG X CGAA AAUAAAUU 4584 AATITATr C TImIGAA 2108 HUM211 3806 LUUXC CUSALXAG X CGAA AGAAUAAA 4585 TIATICr T GGIGAA 2121 HUMR211 3807 CorlAGG CtA=AG X CGAA AUCALU 4586 AAGAT A CIGAAGC 2133 HUMIR211 3808 CAAGAGGU CAJCAG X CGAA ACAG=xr 4587 GAAIGr .C ACCITI 2138 HUMIR211 3809 ALALACA CUGAMAG X CGPA AGGCA 4588 'UCACCT C TIGATIAT 2140 HuMR211 3810 A1AAtC CJIAAG X CGAA AGXXA 4589 CAC=I T GATATP 2144 HUMR211 3811 GUUUPAU CfAr lG X MAA ACAAGG 4590 CIMTIGAT T [A AC 2145 HUMIR211 3812 AGJUUA CMAtUAG X CGAA AALMAGA 4591 TCIT A 'ITAAACr 2147 HUMTR211 3813 UMGUUUA CMAMAG X CGAA AUAAtPA 4592 TIGATTAT C TAAACTA 2149 HiMR211 3814 GCUUAGUU CUAUGG X C:AA AGAULAC 4593 GATItT A AACIAG 2154 HUMIR211 3815 . AmGU CUGADGnG X CGAA AGUJG 4594 TCTAAACr A AGEICA 2161 H1MIR211 3816 AADAAU CMAUGG X CGPA AGCGCULA 4595 TAAhGEO C AICIKTr 2164 MIRf211 3817 UAAAAUG CUGAmGI X CGAA Ampor 4596 G0CIAT T CTAITA 2165 HuMl211 3818 ADAAALA CMAMAG X CGAA AAMEGC 4597 tItITr C 'TITIr 2167 HuMIR211 3819 ULPMAAAA CEAiMG X CGA AGAAmEG 4598 CICATI= A TrrIkTAA 2169 HUMR211 3820 UUUUAUAA CtXmeG X QpA AUAAM 4599 CATIC T TIATsAAA 2170 HUMrR211 3821 GUUUUAt A CAAtmG X CGaA AAUAGAJAU 4600 ATII= T TAAAAC 2171 HuIRF211 3822 UUUAU CmwiAAG X CA.A AAAUAGAA 4601 TICIrrr T ATPAAACA 2172 HUMIR211 3823 UtUUU CtLrAPG X CGAA AAAAUAGL 4602 TCITIT A TAAAACA 2174 HUMR211 3824 ALX UUU CMAMAG X CGAA AUAAAA 4603 'ITrr A AAACAAAT 2183 HMInR211 3825 GCUAAUU CM40MG X CGAA AUUtLUU 4604 AAACAAAT A AATDIC 2187 HbMrR211 3826 AAGAGACU CLAIM X CMA AUUUAXUU 4605 AAATAAT T AGICItrr 2188 HUMTR211 3827 AAAGAGAC ClAMAG X CGPA AAUIALU 4606 AATAAW A GtIrTT 2191 HLMIR211 3828 AMAAAGA CLUAtG X C3PA ACMA=AUU 4607 AAMT rGT C TCTrrrrr 2193 HUMTR211 .3829 AGAAAAAA CMAtGI X GAA AGACUAAU 4608 ATM=GIT C TrIICT 15 HUM1R29 3830 AGAAAGC CMAmGG X CGA ACGu E 4609 G330 T C GITICT 20 HUnR29 3831 GxmAGA CEm Grfl X opA AG=MCG 4610 =GItr T MTrICAC 21 HUR29 3832 GOLTAzG CMrAtG X CGA AAGCmC 4611 GItIT T CTICAA 22 IKMrR29 3833 COMMA CUS.ImlG X 0AA AAAm= 4612 7t33r C TICAACr 24 HUNMf29 3834 GAGU CMtAMG X CGAA AGAAAGC 4613 GGCrIT T CAAC 25 1 DI29 3835 AG =GU CUGAUGG X CDAA AAGAAAG 4614 GCrICrr C AAor1UT 32 HLMfR29 3836 CG3AAGA CLAMG X CGPA AGOOLU 4615 TCAAr C 'Iwittui 34 HtM1R29 3837 Utu3AA CMfAlG X WA AGAGGUU 4616 AACCItT C TittuiA 36 HUMI29 3838 GCEGC CMAMpG X 03AA AGPC3Aan 4617 wiCCT T CCO3C 37 HUMIR29 3839 CKUa= CAL3GAG X CGAA AAGGAM 4618 CtIIC=T C CMM(= 54 HUdM[29 3840 CACUCG CarAUGAG X 0AA AUG 4619 LCtCCAAT C CCGAIG WO 00/61729 PCT/USOO/09721 105 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 79 HUMIR29 3841 CtracC CMAUGAG X MAA ACAGC 4620 GACIGT C CGI 84 hUM29 3842 oCGT CUGAUGPG X CGAA ?LGCGACA 4621 TGICGCGr C G3C C 102 H1UM29 3843 OC CU CAUGAAG X 0AA ACUCG 4622 CWGGAGr C ;ocA= 122 UM29 3844 TAMAUC CMALGAG X CGAA ALUUU 4623 AAAG? A GACAM 126 HUM29 3845 CUGCAJ C AAG X CGAA AUCUACIG 4624 CorAGAT C AXoCAAC 138 HUtM29 3846 ADUUXU CMGALG X CAA AtULJC 4625 GCAACAT A GAAGAAT 147 HUMIR29 3847 LrvU C CtAMPG X CGAA AUUtrLt 4626 GAAGAAAT T GCACA 154 HUIIR29 3848 AALAAUUU CUGAtLAG X CGAA ALGLCAA 4627 TIGCACAT C AAATTATT 159 HUMIR29 3849 UGUTAAU CoGAmGAG X CGA AUU=lm 4628 CA'CAAAT T ATIGAACA 160 HUMIR29 3850 UCLHJUCAA CUGAMAG X CGAA AALUUGAUJ 4629 A'ICAAATr A TIGAACAA 162 HUKMR29 3851 LURJoUC CUGA3 X CGAA AUAAUUM 4630 CAAATAT T CAACAACA 183 HUqM29 3852 UCXGUAAC CtAGG X CGAA AitCtCC 4631 GGGAGAT T GIrACAGA 186 HUMIR29 3853 UCUCtU CMAmpt G X CGAA ACAAUCUC 4632 GATlGT T ACAGAGC 187 HItM29 3854 CTUG CfLr3AG X CGAA AACAAICU 4633 PGATlUrr A CzA 213 HUMIR29 3855 ACAAUCUG CrAAWG X CGAA AUUUE 4634 CAGAAAAT C CACAT 219 HUMIR29 3856 GCITr-AC CMAG X CSAA AUC3GAU 4635 ACCAGAT T GIGACAGC 231 HKMl=29 3857 UUtrMMtC CUGAAG X CGPA AG oU 4636 ACrGCACr T GAdCATAA 235 HUMIR29 3858 GAU A C LAMAG X CGAA AUIMAG 4637 CACTIGAT C ATAATACC 238 HUMIR29 3859 UmG=A CMArAG X CGAA AMAUCAA 4638 TIGAAT A ATACCAA 241 HLMMR29 3860 GCCUUL= CUGAMAG X CGAA AUUfAIA 4639 ACATAAT A CCCAGGC 257 HLMIR29 3861 UrAAUM CLtrLMAG X CGAA ACtCXm 4640 CAAGCAGr T CATlI 258 HUMI29 3862 GTPGAAU CUGAtrlAG X CGA AACUU 4641 AAGCA C ATIUIGC 261 HWM[R29 3863 ULUarAG CMAEG X CGAA AUGACG 4642 CAGIA T CICACAAA 262 HULM29 3864 AIXXI=A CUGAG X CAA AALXACU 4643 AGrICATr C 'IGACAAAT 271 HUMI29 3865 GCLGU CWAG X CGAA AUtUrA 4644 'IGACAAAT C AEGA C 281 HUM29 3866 U1GAGUA CMlrACG X CGAA AGmCC 4645 CGGCr C TACICAA 283 HUM 29 3867 GC2UJGG CoMmeG X CGAA AGG 4646 A0:3= A CITCCAAGC 286 HIEM29 3868 UUTCXm CoLt AG X CGAA AGUAGAr 4647 GCIC T C CAAGrAAA 297 HuMIR29 3869 GaCCGAA CCAUGAG X 0AA ACUUtCU 4648 AGCAAAGr C ArIC 300 HUMIR29 3870 CU33G CGALGD X CGAA AMACIUU 4649 AAAGICAT T CICPD 301 HUMIR29 3871 CCUG3CA CoAUGAG X CGPA AAmLLCLU 4650 AIATr C T1CGG 316 HUMIR29 3872 TAGUG a.DALMG X 0pA ATUM = 4651 GCAAGAT T CCACI 317 HUMTR29 3873 CCJJGLU CtUAG X CGAA AALCXC 4652 GCAAGATr C CACIC= 322 -HUMIM29 3874 U~oCEG CUGAUGAG X 03AA AGUGGA 4653 ATICCAT C C3oAAAA 333 HUMEI29 3875 GUAGGAA CUGAG X CGAA ACUUULICC 4654 G3AAAAGr T TICC=IC 334 HUMIR29 3876 UmAAGA COGAlrG X CGAA AACUUUtC 4655 GAAAAGTT T 'ICCTrCA 335 HMI29 3877 UfLUA CLrAtr-G X 0AA AAACUUUU 4656 AAAAGrr T CCrDOA 336 HUMIR29 3878 GUUAG CMArG X 0AA AAAACUUU 4657 AAAGIIT C CrCAC 339 HLMI29 3879 GGnGUU CMAMAG X CAA AGAAAAC 4658 GrrrI r T ACAA 340 HM[29 3880 UGAoG CMALUG X CCJA AAGAAAA 4659 TrITI A CACItA 346 HtMM29 3881 U3ICAC CE.-Am-AG X 0AA AGLXlAA 4660 TnCAAcr C CAGA' 363 HUMR29 3882 AAcmu aGAMrG X 0AA ACXCC 4661 GCGIr C ACCEPT 371 HUMIR29 3883 UAAAAAAU CMAtrAG X CAA ACUEf 4662 CAAC1= T ATITFIA 372 HIR29 3884 GAAAAA CtLALUG X CGAA APC XJ 4663 AACCAGfr A TITITC 374 HUM29 3885 u230AAA CrAUrPG X CGAA AUAC W 4664 CCAGITAT T TITDrA WO 00/61729 PCT/USOO/09721 1 06 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 375 HUIR29 3886 C LGUAAA CAUAAG X CGAA AAUAAC 4665 CITATr T TITALC 376 iiUrR29 3887 'AGGUAA CUGAUGAG X CGAA AAAAACU 4666 ?GITATIT T TrPACTr 377 HUM29 3888 GP4GGA CtLALAG X CGAA AAAAUAAC 4667 GITATIT T 'IM=CIC 378 HUMIR29 3889 GGAGUT CGAAG X CGAA AAAAAIAA 4668 TIATITIT T ACCCICC 379 HUMTR29 3890 .GGAGUCG CGADSAG X QAA AAAAAAUA 4669 TATITITT A CACIC 385 HUMR29 3891 CAUAIG CtLAMAG X 0:AA AGLtXXAA 4670 TrACCPCr C CIGAIG 391 HUMR29 3892 LLAGACA CUGAWAG X CGAA AUAGGAG 4671 CICCIGAT C TI.CA 395 HUMR29 3893 . GUM=A CMWApG X CGAA ACAGAUCA 4672 'IGACIGr C 'IGCACAAC 414 HUIM29 3894 MCTUUAG CTrAD2AG X 03AA AGCxCPG 4673 CICAG=r C CTAACAGA 417 HDMIR29 3895 UUUC=G CMAMAG X CGAA AGGAC 4674 CAGCI A MCAGATA 424 HUMIR29 3896 UGAGJAAU CUMAtAG X CGAA ACtfUA 4675 TAAC"AT A ATICICCA 427 HUMIR29 3897 GUCLEG CMAUSAG X CGAA AUAt= 4676 CAGTAA T CICCAGAC 428 HtMrR29 3898 GGiUGA CMAG X CGAA AAUIUAlU 4677 AGATAATr C 'ICCAGACC 430 HUMR29 3899 UGU33 CTAUGAG X 0AA AGAAUAU' 4678 ATAATICT C CACCA 448 HUMIR29 3900 AAAAACCU CMUAG X CA]A AUUL=o 4679 GACCAAAT A AGG=ITI 453 HDMMR29 3901 AC AAA CUG AG X CGAA ACCUOAUU 4680 AATAAG T TrIGA'IC 454 HDNM29 3902 AAC-AGAUAA CUGAG X CGAA AAACCUUAU 4681 AATA T TIIG' 455 HUtMR29 3903 AAAGALICA CMAMAG X CGAA AAKCUUA 4682 TAGIT, T 'GAItTT 456 HuMR29 3904 C-AAAGC CUGADGG X SAA AAAACtU 4683 AArM=r T GMITIG 460 HUMTR29 3905 UACAAA CUGALAG X CGAA AUCAAAAA 4684 TrrrIGAT C TIu..m 462 HUMIR29 3906 ACUACGCA CUALUG X CGAA AGAUCAAA 4685 TrIGTCr T 'ICO 463 HUMIR29 3907 UCLPDG CGAUGAG X CGPA AAGAUCAA 4686 TIGMCIr T GCGDG]A 468 HIM[R29 3908 CCACAEAC CUGAUGAG X CGAA ACGCAAAG 4687 CI7Tm r A GIMGI 471 HUM29 3909 UCUCCAA CLGAPG X CGAA ACUOMrA 4688 'IIGOG A 'IGIpAG 488 HUIRM29 3910 GKECCU CU3ADGG X CGPA AIGtCG 4689 CAAAGCAT C AGIC 496 HM29 3911 UCCADAAU CAMeG X 0AA ACGECf 4690 CaGGACG= C ATIMGGA 499 U1R29 3912 UGCUCAU CtALMpG X 0AA ALACGUC 4691 GACGICA T AZAGCA 500 HMIR29 3913 CUGCMC=A CMAUGAG X 0PA AAMPGU 4692 ACGIT A TGADC 510 HtDMR29 3914 UCACAAGU CuAA X aPA ACUCC 4693 GGC G A ACTIGIGA 514 ,HMIR29 3915 'GCCUTc CUGAmeG X CGAA AQUax 4694 CAGIACT T GIGAAC 533 HDWM29 3916 UUUUAAAA CtmAmG X COPA AMtU~M 4695 CAAAT T TrITAAAA 534 HDMIR29 3917 CUPUAA CUAllG X CAA AAUICtXU 4696 AAAGGATr T TrIAAAG 535 HtIUR29 3918 LJUuXAA CIGAWG x CGPA AAAtUr 4697 AATIT T TrAAAGA 536 HMIR29 3919 UtUUUUUA CaL G X 0eA AAAAUCCU 4698 AGGTrir T TAAAA 537 HbMIR29 3920 C0XutJ CULALG X CGAA AAAAAUCC 4699 GGTITT T AAAAGAPG 538 HtMrR29 3921 GCCUUU CUGAMG X AA AAAAAAUr 4700 GATITr A AAAGAADC 549 K-MIM29 3922 UUUXXXUUCG CMAG X CA AIJUML 4701 AGAAGT C CGAAAAAA 559 HKDM29 3923 AUPLMCUA CUGAMAG X CSAA AUULXUTJU 4702 GAAAAAAT T T GA 560 HtMIR29 3924 AAUAUACU C-inMG X C-A AAUXXU 4703 AAAAAAIT T PGIM T 561 KDM29 3925 GAADAUAC CL3GtlG X C3AA AAAXUUXJ 4704 AAAAATr A GATATIC 564 HMIER29 3926 CALAAUA CUGpoAG X CGAA ACUAALU 4705 AATITAGr A TATICMG 566 HUM1R29 3927 GPCLAA CMAMPG X 0AA AUPLIAA 4706 TITGIAT A IC'IGIC 568 HMIR29 3928 UCfbCAUG CMAMAG X COA AUAUACA 4707 TAGT T CAMGIG 569 HtMMR29 3929 CtDGPCAU CUGAmG x CGPA AAUAUACU 4708 AGIMMT C AGICGAG 574 Hlr'R29 3930 LGAUCCUC CMALUAG X AA CAUGAAU 4709 ATICA=T C CKGA WO 00/61729 PCT/US0O/09721 1 Q7 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-1 I Orphan Receptor Genes 581 HIMIR29 3931 AAIUUU CCGAUAG X CAA AULtUCA 4710 'GPMAT C AA TP= 589 HUIR29 3932 AMPALAC CtAGAG X CGA AUCCU 4711 CAAGGAT T GATAT 592 :-.UIR29 3933 AUUAAIAA CUGAUGL X CGAA ACAAUTCU 4712 AGATIGT A TrATIAAT 594 HU M29 3934 UTPUAAU CGAUGfl X CGAA AMUCAAC 4713 GATI T T ATTAATAA 595 HU4Mr29 3935 CUUAAA CUGAUGAG X CAA AAUACAAU 4714 ATIGATr A TrAATAG 597 HUMIR29 3936 LGCUUAUU CGAUG X GAA AUAAUACA 4715 TGTATIAT T AATAA 598 h-HUjMR29 3937 GLGCUUAU CLGAmG X CAA AAUAAIPC 4716 GATIT A ATAArC 601 HMUrR29 3938 GLU=CU CALJG X CGAA AUUAALAA. 4717 TrATMAT A ACACCAC 622 HUMfR29 3939 GCAGUUU CXALUG X CGAA ADG U 4718 ACCDXIGr C AAACI 626 HJMIR29 3940 AUCG CLAWAG X CGAA AUGOCG 4719 CIGICAAT A CIGCAGGT 635 HM29 3941 AU=UG CCGAMAG X CGAA ACUG 4720 CIGCAr T ACPAGAT 636 HUMrR29 3942 CAUCLXG CMAMAG X CG-AA AACCUOCA 4721 'IGCLI A CAGAGIG 646 HUM29 3943 AAACGCAA CUGAUGAG X CGAA ACAULCCU 4722 ACN3MG A TIGrrr 648. HUMIR29 3944 CCAAACGC CUGAUAG X CAA AIBCA 4723 AGAT T uGTu 653 HtMIR29 3945 UrAUUC CUGALAG X CGAA ACOCAAA 4724 TATIGCr T 'IGAMCA 654 HUMI29 3946 UrA=uC CUGAUGAG X CAA AA3CAA-J 4725 ATIGC=I T GGAAGAA 671 HMIR29 3947 AUGGACA CCGAUGAG X CGAA AGCCUT 4726 GAACT C 'IGICAAT 675 HTRF29 3948 UCACAUM CMAMAG X CGA ACA T 4727 GACICIur C CAAGIA 696 HUMIR29 3949 GALCUC CCGAUGAG X 0AA AUCM =UU 4728 AAMCAT T GAPwMC 702 HUMI29 3950 LUX ACX CAMAG X GAA ACtUCAAU 4729 -ATIGAGr A 'ICACGC A 704 HI'R29 3951 UUUCDLG CUGAUG X 03AA. AtacDUCA 4730 'TGAAT C ACGABAA 716 HLM29 3952 AGUGGAA CUGAMAG X cAA AUUUUU 4731 AGAAAAAT C TICCAACr 718 HUM29 3953 ACGUUGG CGAUG X CkA AGAUUUUU 4732 AAAAA'ICT T CCAACIG 719 HtM29 3954 CACAGULG CUGMAG X CGPA AAGAUUU 4733 AAAA'IC'T C CACIGIG 733 HUMrg29 3955 ULGUM CMrAMG X CGA A AC 4734 GIGECt T CAACAAA. 734 HuIM29 3956 UUC=UU CUGA9rdl X CGA AAGCC 4735 'TGCCGI C AACAGAAA 747 HUMIR29 3957 CCGAAUA CUMAtG X CGPA AUUUUUUC 4736 GAAAAAAT C TATAI 749 HTMIR29 3958 ULCMADA CMAMAG X CMPA AGAUUUU 4737 AAAAA' A VTCrA 751_ HUM29 3959 CTUXCJGA CGAtMG X CGPA AUAGADUU 4738 AAA'CAT A 'IurMAPG 753 HUIR29 3960 UTUUUCG CUGALIA X C3AA AIMLMGAIU 4739 A'TTAT C CGAAGA 765 HLMtR29 3961 G33CUCG CUGAtLEG X C A AGGtCU 4740 AGr T CGTPB C 766 HUM29 3962 U0mCL CtAIUG X CIPA AM =UTU 4741 0AMrrr C GrGarA 769 HJMIR29 3963 UA13C CtAmeG X CXPA ALGMCG 4742 4rrICT A CCMTA 776 HLMTR29 3964 IIDtGUU CUMMAG X CGAA AUGllaA 4743 TPDCCAT T AACIGA 777 HKIAR29 3965 GUOCPU C IAG X 0PA AAn3U 4744 AGCcT A ACIGC 787 HUKM29 3966 AAAA= CEAtJG X CMA AGUoLC03 4745 CIGCAACT C CAAcr1Tr 793 HUMR29 3967 tGUUmCAA CtflrGlG X CSA AGUEGNA 4746 CItrAAC T TIGAnCA 794 HIRM29 3968 CDUACA CUAUGPG X CAA AAGUCIGA 4747 'CCAALTr T 'IAACAG 795 HUMFIR29 3969 UaGUUPC CoMrAG X GPA AAAGUCC 4748 CCMAr T GAPCAN 798 HUMIR29 3970 CLX U CMUG G X CDA ACAAANGJ 4749 ACTIr A AOGATG 805 H1MIR29 3971 ACUUtrAC CGMrALG X MNA AMUt UA 4750 TACNAT A GIGMAAD 814 HLUIR29 3972 tMCUG CUrAG X AA ACUUUCC 4751 GIGAAAGr A CAGICA 821 HUMI29 3973 GtCtUU CUALrM X CGAA ACCLtUtA 4752 T1CAAT C APGGC 833 HUMR29 3974 CfLAAUCU CEXMG X AA ACM U 4753. AMCIGT T AGATICPG 834 HUMrR29 3975 Cr.AAUr crAtmG X CPA ACA=UCL 4754 GGACI6rr A GTIC WO 00/61729 PCTUSOO/09721 1 08 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-l 1 Orphan Receptor Genes I838 HtJIUR9 3976 CAUrxct =UA X OGAA ?LauvcA 4755 =GI.AT T -AMMIM I839 hUCWR29 3977 ACAI~U CtMAfLZ? X CSAA ?1AUflU.P 4756 GTLAT C PZGANAt= 848 MU M~9 3978 t~UAUrCA CMflAflAL X CGAA ACAUE.C 4757 AL-AA 1~T T CAITGAATA L849 MUMR9 3979 AUAUUtAU CMAUGAG X 03A AACAUULC 4758 GAA TT C AdGAATAT 856 KmRI~29 3980 tJ33LIX3AA CMfAiLGAG X OSA 1~JAU XPM 4759 TCATGAT A 'f'ICA S858 Ht1M9 3981 GALfl3AX CLMMlG X CGA AILMtUMt 4760 ATGA~AT T CA~TCAM 859 PuqM9 3982 ~ALU CMAWAlG X 0AA AAUULtrA 4761 'IGAATATr C A=TCr 862 HUM9 3983 LMPAMJ CtMAMIAG~ X CGAA [AMAUAU 4762 -AM=I T C CAWIUGA 866 HtM9 3984 UUACt C cXAIA X CUA ALMAfLMi 4763 'ICAITc C TIGEGAA 873 HtxrR29 3985 LrM=ut CMALZflG X OSA ALC. 4764 TCCr-AGT A AA=I 884 HEfLVM9 3986 GZCA Ua CU3AIXW X CtGAA ACXAG1tJ 4765 AACIGAT C ?XIMI 902 H~rR29 3987 CjtUALUJ CrflMJfl X 03A ALUM=ri~ 4766 GAMGACAT C AGTAG 907 HUMtI29 3988 UtrttJ QflAMAlG X CGA ?AfLAMf 4767 CATCPAA A AG3LIGA 917 HUMIR29 3989 CCMAlCAU CMALZA X 03A AUtCAGC 4768 GDZIGAAT C ATM=C 922 ,HZMnR9 3990 .Airrttt C MAMAG~ X 03AA ACAMLU~r 4769 AATC=~ C AG3WT 931 HLIKtM9 3991 tflACLAt CMAUX3 X 03AA AtrttJ= 4770 A3MAMT T TAA 932 HM=1~9 3992 AUGUACUU CflAMfl X OMA AALtC 4771 GOC-Tr T AAGMCA 933 HtIflM9 3993 AAtfLPO1 LU M1X3 X O@AA AAAIL= 4772 GSATI A AGAAT 937 H!'fl99 3994 GGCAAfl CMfAMXAG X CSAA ACLEPAA 4773 ATITAA~r A CAM=~ 941 HU2 9 3995 CAUtXlf axU.tnG X 03A AUGlPL JE 4774 AArACAT T GXCCATG 954 H.MJR29 3996 AAtflAUGU CLAnMn X 03A ACCAIXJ 4775 AAMtI2r T ACAT= 955 Ht1MM~9 3997 UkqrflAAM CtLrAUClA X 0CA AACCACXU 4776 ATIZI=I A CA ICATMA 959 HUMTR9 3998 Utmx1AAf trAnUinG X 03AA AMMAWC 4777 cxrrMcAT C ATLADOC 962 HUItR29 3999 GALX=U CMUMA X CGA AMfl0GUA 4778 TACA=~ T AGGALC 963 HMf~9 4000 AcGAUtLC CMfAtflG X CXMA AAIMIfl 4779 ACAT= A GGAA=C 970 HliM9 4001 UUULtECIA aflMtfl X 03A AUUMJt 4780 T~AGOG C IIAAAA S972 H1'lI29 4002 GIUW=CMAnMin X CGA AM =t~ 4781 aAAW= T GGAAAAAC 982 HuDR29 4003 APC-A= CflArLEA X Cr-A AGUJUU1X 4782 GAAAAACI A AA.C-AI 988 HMl9 4004 UtL13AAAA CMfAtL X 03AA AMMAGP 4783 M~AAAGAT C. ItIA 990 HUAM29 4005 tUXXfl CLGAIfl43 X CGA AGAUCUUU 4784 AAAGAT T TWIUAAA 991 HLIM29 4006 AflUXJt4L CUGAWIflG X =A AAGA=X 4785 APA IT T CICAAAAT 992 HKtflM9 4007 twUAUrA CMfALAG X OMA AAPGA=E 4786 AGATrrr C TAAAA1k 994 HLZMR29 4008 ACUAMU CMfAIGA X CGPA PAGAAA 4787 ATriwr C AAA 1000 MUM2 '4009 UtMLxkC Ctn flAL X CCA ALUXXPG 4788 CIMAMAT A GM kAMAA 1003 HIMER9 4010 CA1UtAL CMAUGAG X COA ACUtIXXX3 4789 AAAA=IG A ATCAAATG 1013 HuMM~9 4011 aWEUA Ct.MM X Cr-A AaUXE 4790 ItAAA=~ C tadGI 1015 KIUM9 4012 ULrrAAUC CttAUCAGL X 03A W3CACIXX 4791 AAAMtI= A 1GLrIGAA 1020 HMMf~9 4013 AGUUJE Ctr.AfLr-J X 03A ALMM 4792 wIC.M i T GAAIT 1028 MCMfF.9 4014 CAUUXCUU CMfAMflG X C aA AGCUUECA 4793 TGAA~ T A~AG 1029 HUMIRf29 4015 tCAUtfl CfLrAWfl2 X cSAA AAGCUOX 4794 GAAI' A A GG 1042 KJMIR29 4016 CAAGAG CtLUAUA X 03A MALX fl 4795 ATGA IGAT A CCICITI 1046 HtKM29 4017 CACAAA CtLEAtfl X CSAA AGGAUA 4796 ~TG LCI' C TITGIG 1048 Ht1'flR29 4018 tUtACA Ctr-Atfl X 0MA PCAG 4797 AIR T MIUMMIA 1049 HINff99 4019 AUtM.CAK CMEIAG X 03AAC ~ 4798 TAL'IT= T GIVG"A 1058 RXUM9 4020 ULIUEM. CfLrAtLrAG x CGA AtXEOE 4799 Gf IGIAT T MkA CAAA WO 00/61729 PCT/USOO/09721 109 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-l 1 Orphan Receptor Genes F-1059 MUvM.9 4021 AXX=tf CMAMAlP X CGA AAUtrACA 4800 T~lrXFA T C-AAA !060 P LX-29 4022 CA~UtU= CMAMAL X CCAA AAAIUtrC 4801 -GIC-AJTr C AGA.AAM 1-2086 hiUCRE29 4023 GCULrA CtfAfLEPL X CAA -A=A=r 4802 GGIA-mW T WCAPG 1087 HZIMl29 4024 UOCUW CUflAMfl X CCAA AAAUCC 4803 GMG=~I T CAG 1088 h1ZnR29 4025 AMC= CMMA X CGA AACL 4804 MT =~r C AA33A 1097 HUivER9 4026 C.GJfLrA CU3ALX31Z X CGAA ALXtUU 4805 AAG3C3AT T CPCIC= 1098 HUDMrR29 4027 AM =~n CflAX3A X CX3AA AAU03= 4806 A03XXA= T GACACIC 1105 RUM~9 4028 UUXXtrAA GflAMOG X CGAA ?GJGLAA 4807 'rIGACrC C TIGAAAA 1107 HtM1R29 4029 GCUUtUG CMfALEfL3 X CMA AJfl= 4808 GC-AC tT T GCAAAAK3 1118 HLMMH9 4030 C. A t CtLUBAG X CC3AA ALGXUUWU 4809 AA~AAG T G-AAT= 1123 1M R29 4031 Ctt!CCA CUCAfLr-G X 05A AUErAALX3 4810 CATIAAT C CIOGGA 1L151 HtFIZW29 4032 COCLAcU CflAIflAL X CCAA AGCtrtM 4811 CCPG-= C PflrA= 1155 HU-Ml~9 4033 AU3C CMALUAG X CGAA AMM=~ 4812 AICG= A 033 1176 HtI-flR29 4034 A3EU fl CMfAWLG X CAA ACCE 4813 mGGiA r A CACAT 1182 K.RqMl~9 4035 Cr.-%nA CtflW1G X C A AGLGA 4814 GC1' A JAA 1185 8UHLZ 9 4036 UnCUcM i CflAUGA X CGA AUtJGGfl 4815 CACMC C X70Sa 1195 KU~24m 4037 UAIJU f CMfAMflG X CMA AM=lt~ 4816 CGCPT T CAAT A 1196 HUMI 29 4038 Ut.AL=U CUMAGL X CGAA AALU= 4817 'IGSA= C AGAMA 1203 HI~LZ.9 4039 GUGUAAUU CMAMPG~ X CC@A AUGUIMA 4818 MAA= A XATMLAC 1207. K~IR9 4040 LIM=fl CUAMA X CGAA AIJXX=t 4819 GCATAAAT T ?ACtACC 1208 HtJMM~9 4041 UUEaY CMAM3AE X CSA AAXXMMf 4820 CAM=AT A CACWrA 1230 HUZM9 4042 LL1CM CtflMflP X CMA AGLUG=t 4821 G3JXC~ T CICGCG 1231 HUMIP.9 4043 AIU00= CMUAGfl X CAA AA3CC 4822 G3CA~IT C TCG 1233 HM1R29 4044 GAU=t CMnAUflA X 03AA AG 33 4823 CCCI' C PG03= 1240 HLEM29 4045 UACAUGU3 CMfAUflPG X 03AA AM M 4824 TCA= T CAIG= 1241 HUIRn29 4046 CUACAILUJ fLEAtflG X 03A AA0X 4825 CAGCGTr C AC = 1248 HtI'n99 4047 CUflAAG CtLrAE X 0MA ACLM 4826 'IcA A GITIw 1252 HUMflM9 4048 GGCCtG CMfAflG X CMA AGCCAU 4827 AM= T TLXA IC 1253 924M9 4049 MPG=tJ CLM X C AA AAGCMA 4828 IG rr T C1AGI=A 1254 MUR29 4050 GUl~z= aflLrAM X OMA AAGCLC 4829 GM=IT C AMMC 1260 HMM~9 4051 GOCAUGUJ C3AGA X Cr-A AOCCI31A 4830 TIAI= C ACA=I~ 1270 M1r29 4052 CANGA CUGAtrz X 03A AGGAU3 4831 CO= T CMtMAXI 1271 HtxI29 4053 GCLM CflAIlG X 03AA A0Lf 4832 CAM=I' C MZ1=~ 1273 HUr29 .4054 AGOCUA CflM1XG X 03A AGAAGGCA 4833 =.PIWI C cnu=~ 1276 HU=29 4055 CUCAGMA CUAUGAG X CGA AGAGA 4834 CrCi A TGCC7G 1286 HuMn29 4056 CALUrrM CUAA X OMA AKIXM 4835 GCIGAM A CC7GAA1G 1301 HUN1M9 4057 CCOAtfl CUGAtLUAG X 03MA )Gfl3C 4836 TG1IG A CAT~ 1305 HUN29 4058 GC-AC-- CUflA1X= X CGA AUflMLU 4837 CAMICAT T G3:2 1313 KIM29 4059 U3MG3CA CLUAtflAG X CGA ACX~ 4838 T03GAr C ~ITul 1319 HL!IlM9 4060 Gflt X CWAlLGAG X 03A AMMM 4839 aitCr C CCGt= 1331 HuM29 4061 UWfLAIG~ CAnM.rn X 0A ACAGG 4840 ACIGi= T CrnTM 1332 HUEM9 4062 ALJWUAA CMfAMAG X QGAA AA2GA 4841 CI70IGI C TMCAAT 1334 HUMwR29 4063 GCAUflAU CtLlUG3 X (3AA AGP 4842 CI01i'tT T ACA= 1335 HMIF.9 4064 UOCXMf GflAtLZAG X C3AA AAAA 4843 CII'IT A TWAAWA F 1337 - MrR29 4065 ZAa11Jt CfaM flW X CXAA MA&WAP 4844 G=I=. C A=A~Cr WO 00/61729 PCTIUSOO/09721 110 Table IV. Hammerhead Ribozymes to TR2-9 and TR2- 11 Orphan Receptor Genes 1353 HUEfl29 4066 GCAM CMfAUC-AG X CGA kGLD=c 4845 TGOMAr 1354 R MR2 9 4067 ;GANLM CtNL = X CGA AAL 4846 G00=1 7 ATI=r S1355 -lZ~ffR29 4068 AAGAA CUSALA X MAA AAG= 4847 ~CFITAL C GAT=CI 1359 HtfL'R29 4069 AAACAAGG CMfAtL)GA X CGAA Am3U.AAA 4848 CITItMAT 7 CCItrIT 1360 HU1flM29 4070 C-ACAA CfLEAMPC~ X 03AA AAIOGAAA 4849 TFtlr C CrILr'i 1363 HLNM9 4072. MCtAAAG CUCALAG X CGA ~AA= 4850 LGATiW : Criitc. 1364 HUVflM9 4072 CCtUlAA C U CA :GA X CGA AAGGAAIC 4851 GATT C T'iic=~ 1366 KMERv~l29 4073 A13CXXA CUGAMAl3 X CGA AGGA 4852 TICCI'ItTCP 1367 HU.h'MR9 4074 CGDCtfl3 CtXALJ2A X CflAA APAC 4853 'IWIWIT AG 1368 HMIM29 4075 -CAC=J CMfAMAG X CGAA AA1AWX 4854 CIrIT 2 CZAI3 r 175 Et4R29 4076 UEttXA CUfAMAGP X £AA AGCCUW- 4855 TCA( TmLfXA 1377 HtIkM9 4077 uunxc CfL.LG X CGAA AGtAfl 4856 CAG =-- 00crA 1395 HUM1R29 4078 ACCfAGL CMXAMflA X OSA AMC=OJ 4857 AACAC.AT A 1-rC=~ 1397 Hffl29 4079 MrMAGU CUSAWAGL X GGMA A1L=E 4858 CAGCAAT C A M 1411 HUMnM29 4080 AUtCA3J CtrA=~ X 03A AGCXtA 4859 'IGAAG=T A=A 1412 HEM1=9 4081. c~flu=P mm 13~ X C&A AA2JtJE1C 4860 CAA=T a CIGMAM 1425 HUr29 4082 AGAGAAA CMfAIUiAG X CrAA AXrULXJA 4861 AAMIAA~rT TIM 1426 HLZEfl29 4083 AAGGLIA ct 1~2A3 X CtiPA AACJX=I 4862 ATGAACIT -IM 1427 HUIMR99 4084 CAGiGU CMJ3U30LZ X 03AA AMC=E~ 4863 =AACrIT: TIKTI= 1428 KUN=9 4085 CCAAGA CMfAtflG X 0AA AAA=f 4864 GAAC= 7AMC 1429 K&MI~9 4086 ACAA CtLGAGfl X CCA AAAAGLJ 4865 AALrrI= A CI~ri= 1432 I'M9 4087 AAWA)LCAA CfLALMG X CMA AGUAAAA 4866 TrIrm~cT C TIM=~ 1434 HtIM29 4088 GCAACW CUCq]AG X 03A ACIAA 4867 TrIAP= T r Giuri' 1438 HUEM9 4089 CU333AA CMfAtLUA X 03A ACCAAM 4868 C1tTr C TTOCtM 1440 HLN1M29 4090 CACt= CtflMIfl X CCA AGAA 4869 CI~TG - (7GCCA= 1467 HtU-29 4091. ALPXL3 aflAtflA X GSA AM =EA 4870 ALIGAA=f ~a~cm 1474 Kt1EMF9 4092 U~Mt CtLr-1.GG X CGAA AGUU= 4871 TACCT ULMA 1476 HuMIM29 4093 GUcIAA CM-W)GAG X 03A AMC=~t 4872 GACAT MGAC 1478 HLkflM9 4094 AULf= CLOAtflG X 03A AUAUAGUU 4873 AC1=T AGCACAT 1479 KMUMl~9 4095 AAU=J CfLrAflLrP X CA AAI~UG 484Z.r ~~I 1487 aKI~29 4096 AXMGWCA CMUAG X 03A AM =J~tt 4875 AWACM~ T m=CAATr 1488 iumfq2 4097 cawmnc ctflIrfwL x a;A Am==l~t 4876 G~A T MICA='I 1491 HLIk=9 4098 AGCAAIXJ CLEAIXAG X 03A ACZAAIJ3J 4877 ~AATI= C MAT I = 1495 HM 1;29 .4099 GflAAGAC CtMAEX3 X C MA AMtGA 4878 TIGIMAAT 'GICI= 1498 HUNM29 4100 A1XXUMA CUIGAMl X CMA PAUMAl 4879 ICAATI= C TICAAAT 1500 HU~flM9 4101 CAD=tn CtflAIflG X CIA PGACAIEJ 4880 AATI=ICT. C~A.AA 1501 IitIflM9 4102 ArCUAUir CMAAG X Ox A AGCAAU 4881 ATM=cr C ACAA=I~ 1507 Hu1,I29 4103 Uro.WAC CWfAWflPL X 03A AUtflAA 4882 TICACAAN GICTCAA 152.0 HUMM~9 4104 UtflirAA CtGAU2A X 03AA ALCUUfl 4883 AMA=I C TICAAiAA 1512 HUI29 4105 GCjtfl1W CMfAGAG X CM AC4CPALW 4884 AA301ur T CACAG 1513 HUM9 4106 tUmjU3L CMtfLr- X CSA AAGLaW 4885 AI~TIT C -kCAGCA 1529 K-uM29 4107 AAGLAU CMfAGAG X CtAA ALC==t 4886 AGAG A ACIT 1532 Ht1flM9 42.08 ULUkkGGU CfL~qA X OGA AXM= 4887 GMZAT C ACI'AA 1537 924M9 4109 C4CM=t CAnIGA X CGA .AGLMU 4888 AMU=~c T AAAIU= 1538 Hb=~9 4110 uaw=IUE CtwflrL3 x a:A Amamu 4889 AMA=t~I A AAAdMIC WO 00/61729 PCT/USOO/09721 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 1545 E-LIM29 4111 UUUUGAU CLGALUAG X CGAA O'AUUUUA 4890 TAAAATU= C ATCAAAAA 1548 tJMIR29 4112 CUADOUUU CrAULPG X CAA AGACAUU 4891 AATGICAT C AAAAATPG 1555 HUMR29 4113 AGUAGAUC CLALAG X CGAA AUUUUfLA 4892 TC.AAAAT A GACACT 1559 HUMIR29 4114 UCUaU CGAG X CGAA AUCLMUU 4893 AAATAGAT C TACTAGAA 1561 HUMIR29 4115 CCU AG CtAfLZG X CGAA GAUAU 4894- ATAGATCr A CTAGAAG 1564 HtMIR29 4116 CICCUUC CMAUG X CGAA PGAGAC 4895 GATCrACr A GAPOAG 1576 HUMIR29 4117 CGATU= CMAWAG X CGAA ADGCLC 4896 GGCAGCAT C ACATIr 1581 HUMTR29 4118 AAGA=GG CMAWAG X CGAA AmUlAU 4897 CATCACAT T CCCATCT= 1582 MIRM29 4119 UAAGAG CfLAMAG X CGAA AAUGLrAU 4898 ATCACATr C CCATCTIA 1587 HaMIR29 4120 AUAAGUAA CtLALMAG X CGAA AIMAAU 4899 ATICCAT C TITAT 1589 HKM1R29 4121 CADAAGJ CGAUGAG X CGAA AGAUItA 4900 TCCCAT=r T ACTING 1590 HU1TR29 4122 LLrCAUAG CUGAUGG X CGAA AAGAIG 4901 tATC r A CPM A 1593 HtIRZ29 4123 GAGAU CttAmLeG X CGAA GJAAGAU 4902 ATUITACT T AmACIC 1594 HUMIR29 4124 G CA CtXAG X 0AA AAGUAAGA 4903 CITPCIT A T C C 1601 HUMIR29 4125 PGGLG CULGAG X AA AGUCCAUA 4904 mAGGCr C CmTC 1604 HUIRM29 4126 - flCA3 CtLADGG X CGAA AGC 4905 GGACIC r A uC Iur 1613 HtMt29 4127 AAGACAU CUGAWAG X CGA ACCAG3G 4906 CCCCiGr T CATGICIT 1614 HtMrR29 4128 UAAGACAU CUGAUGAG X CGAA AACCAlm 4907 CCCICM= C ATGCI 1619 HUfMI29 4129 GCAUAUAA CA AG X CGAA PCAUAC 4908 GI'ICA=Ur C TTAT 1621 HDMI29 4130 AGA CUGIAMAG X CGAA AGPCAMA 4909 TCAIGICT T ATATG 1622 HUMrR29 4131 CzG3CAUA CUGAMLG X CAA AAGACRG 4910 CATGI=rr A TATIG 1624 HDNIR29 4132 UACA0CA CUGA G X MAA AUAAGACA 4911 TIIAT A TGCCIGIA 1632 HUDMr29 4133 AUAACAU CMAmGG X CGAA ACACPU 4912 ATGCCIG A ATGITT 1638 HDMIR29 4134 GCUUUAU CLAUGAG X CGAA ACCAUAC 4913 GI!AA T ATAAAGCC 1639 HtK['R29 4135 3uutA CMUAmG X AA AACCADUA 4914 TAAaIrI A TAAACr 1641 HUMM29 4136 GaGGU CUAG X CGAA AUAPCCAU 4915 AGGIAT A AGCDCIC 1648 HDqMf29 4137 CCOAJM CMAMAG X CGAA GCUPA 4916 TAACto A CrrICAI 1652 HtMIR29 4138 CUutr CUoUAG X CGAA AGUpAr 4917 GCCIACTr T CAGAAG 1653 HUMIP29 4139 GCrOUCcu CMAMpG X CGAA AAG3Gp 4918 CrC C AGGAA1DC 1663 HUMI29 4140 GLACA CtMAG X CGAA AGCOU[I 4919 MAM= A -1u9n=C 1668 HtMR29 4141 AAUUAG C GX fAIX CAA A CAG 4920 GCIM T GCDAT 1673 HMIR429 4142 UUAGUAAU CMAtMm X CGA AG[IAAC 4921 WIGPer A ATTA 1676 HUMR29 4143 CCAUJGU CMl GAG X CGA AUUAGr A 4922 TGCrAAT T ACA 1677 HUEMR29 4144 UtaUAG CMAAG X CMA AAUUG= 4923 GACTATr A CI!ATGOA 1680 HDME29 4145 CCAtCCAU CMAIXW X CGAA PGAAUA 4924 TAATDCT A AiMt 1691 HtMIR29 4146 AtLNXUUA COLEAmGG x CGA ACCCAUC 4925 A G T TIAT 1692 HDM1R29 4147 CAUGtUA CGAUGPG X CGAA AACCACX 4926 GATG r T TAAACAT 1693 HtMI29 4148 ACAtUUU CMAMPG X CGAA AAACCAU 4927 AG3IT T AAACAI 1694 HUMR29 4149 GACAtULU CMAtLU X AA AAACCCA 4928 I0IT3 T A AATGIC 1702 HLMR29 4150 tnCG CUGAMeG X CG1A ACATUUU 4929 AAACATGT C CCICn;CA 1706 HMtIR29 4151 UUAUGA CUGlA1G X CGA AGACA 4930 ATGICTt C TPCAATAA 1708 HUMIR29 4152 AUUAUUG CW AUGPG X CGPA AG AGmC 4931 GITCCICT A CATAAAT 1713 HUMMR29 4153 UUUUAAUU CMAWrG X CGAA ALESUAGA 4932 TCI;CAAT A AATnkAAA 1717 HUMIR29 4154 AAGAIXXU C= t lL G X AA AUUUtM 4933 CAATAAAT T AAAATCIT 1718 HIZR29 4155 AAAGADUU C-A.irG X CAA ADUCAUU 4934 AATATr A AAATIT WO 00/61729 PCT/USOO/09721 112 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 1723 HUMIR29 4156 CAUL"AAA CMGfAU X CGAA AXXLTAAJ 4935 ATrAAAAT C TrICAAIG 1725 Ur229 4157 AACAUUGA CUGALGAG X CGAA ;AfUUA 4936 TAAAMCT T CAAI 1726 HUMIR29 4158 AAACAUUG CUGAUGG X CGAA AAGAUUUU 4937 AAAAMIT T CAAT 1727 HUMIr29 4159 CAAACAU CUGAfAG X 03A AAAGAIUU 4938 AAAMCIT C AAMT~IG 1733 HuMTR29 4160 UAUADUCA CGAUAG X S AA CUAA 4939 TICAAGI T 'IGAATATA 1734 HU4MR29 4161 UUALUC CMAmAPG X CGAA AACAUrA 4940 'ICAAMIl T GAATATA 1739. H.MPR29 4162 ACAUUAL CUGAMAG X CGAA ADUCAAAC 4941 GIrIGAAT A TAMGIGG 1741 HMrR29 4163 CCCACAU CMAUGAG X CGAA AAUUCA 4942 TIGAATAT A AITMs 1754 HUMtR29 4164 CAGU JA CUJGAUAG X CGAA ACACCtX 4943 GCKIGr T TALrIGAG 1755 HUMI29 4165 CUrCGU CUSAMPG X CGAA AAC trm 4944 GAIGIT T ACCIGAGG 1756 KUMIR29 4166 CITUCAm CtLAMOG X CGPA AAACACCU 4945 AGGIr A CCIGA3G 1768 HUM29 4167 GPCAUAGA CUGAUAG X CAA AM3CC 4946 GKCncT C 'CICI 1770 HU!MM29 4168 GGGAUA CUCAUAG X CGAA AGMtI 4947 G3CICT C TATCL 1772. HUMIR29 4169 CM GPA CMAMPG X CGAA AGArGC 4948 a.1cUlrc A ICICCG 1774 HU-Mn29 4170 UJIf3A CMAMAG X CGAA ALPG 4949 CICICIAT C 'ICCCOAA 1776 HLMIR29 4171 AAUU3G2 CtALpLG X CGAA AGAUkG - 4950 CICDrT C CCCAATr Where "X" represents stem II region of a HH ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20: 3252). The length of stem II may be > 2 base-pairs.

WO 00/61729 PCT/USOO/09721 Table V. Hammerhea, )ozymes to EAR3/COUP-TF- 1 113 PCs Se. I.D. Se. .D Substrate NO._ ba. _ __ _ _ 16 4951 AAALr~:A CUPMAG X CI:A AL13CA 5248 TGIUT T Mr-IGA'r 17 4952 AAAMOG~ CUALA X CMA AA33C 5i249 MW=AT T CXAl= 18 4953 CAAAC LI ctMuG X CMA AAU33C 5250 IM'IT c i7rrx 23 4954 AGLX1A CtJMLIP X CCA AMMAA 5251 TIWIGAT T TIOCAACr 24 4955 AA-U3 aXE3 X CCA AAUCAGAA 5252 TIt'IGATr T MOW=CI 25 4956 CAGUtM CUALxUA X 03AA.A= 5253 TCIGTI= T GCACI= 32 4957 tL=X CULXK:P X CIA AGXUOA 5254 'rIUOr T 033AG 65 4958 030A CUAUA X CMAGU= 5255 AGrP T GCrIC 69 4959 CO3 CLPMr X CGAGC 5256 AGTIrI C GC33 154 4960 CxtCCO CUMDM X C13A ACCU 5257 A~GG T T3333 275 4961 GC= otrMzG X CM.A A=.r 5258 GGCPr A G3C 317 4962 C~%GO QCiLXAG x aA ACC 5259 GC3 C C33Ir 323 4963 cxGAG CGAUGiG x am oom 5260 GCiCr C G33:7= 329 4964 CAGAO CAMAG X CA AGC0A 5261 CIUGrO C G3I 334 4965 GGOOA GfLU;G X COA AGOA 5262 OCIUr C CIUCAC 373 4966 G3M xULM X IA G33 5263 030 C COC 379 4967 GkG3 CLXA= X CA A033 5264 MCC= c C CM= 386 4968 GM= CEMIX2 X CMA A03= 5265 IttCtt T CtWI'I= 387 4969 G3AG CUGALMG X 03RA AA333 5266 Ct'IT C UIIT 392 4970 GGA~AG CUAUA X COA AG3M 5267 crI7C= T MO=I 393 4971 G33AAM CUAUGAL X CA AAG33A 5268 TICrr c coc1= 398 4972 GOGAG33 CIALXG X COAA3GA 5269 CIC=~ T COC 399 4973 =tC CUaVMG X 03AAOA 5270 TICO= Cc== 404 4974 C33 CLXXXP X C3AG3k 5271 crICr C CAO0 433 4975 LtMK= arLIML7 X COAG3 5272 G033 C G33AC 445 4976 GtCP CU tx X 0:AACO 5273 GAC~ C G3CI= 450 4977 GL33 CUAM X C3A AGCOAG 5274 GMAI'r C COCC 462 49'78 GMX KU); X 3A AGJ 5275 CCG C -- X 478 4979 CAIOOC CaiwX2 K O: AICXXZZ1 5276 CCAAT A IUCAI 489 4980 CL~I~aMC aJIGXMG K CA AC=III 5277 GCA= A GTDA 492 4981 CG!UW a3ULX3 X CA~A APPXZ 5278 AIGG= T AQ 493 4982 CCa CUAM X CM ~c~c 5279 A GIT A 508 4983 GLX CUAUGAG~ X OM ALtn.= 5280 G3MA C C3G 614 4984 CL.13M K CGA AGO 5281 G0=C G303 706 4985 Ca33 CLx3M)M K OA AC33 5282 C 1-.r--,T TC3= 707 4986 UtX3= CUEUG X 03A AAO 5283 OCCrr C G30C~ 729 4987 ACCAU CUALwIM X C3A AUEMC 5284 -COAA C GAGIUr 755 4988 UX303= MGM X A ALUl= 5285 GGCAr C GA03= 770 4989 AME= CUAUGA X OA ALGXfl 5286 CAG A C330O 779 4990 COMG= CU x2 X M A 5287 C33=AT T CAC 780 4991 U a3t7 KLGD X 3A AAU33 5288 GOCArC AC=Ui 802 4992 CU AGrA KUAUA X A ACLTxn 5289 GCAAAM T ~TrICAA 803 4993 MXPA KUAI2 X 3A AACU= 5290 CAAAG~ T CIA 804 4994 CaXXA CUACMxG X CA AAAC=J 5291 AAArI' C TIAAGA 806 4995 == anip x cA Apuj 5292 A~ArrT= T awA~ WO 00/61729 PCTUSOO/09721 Table V. HammerheaL .,Abozymes to EAR3/COUP-TF- 1 114 807 4996 MOW=u CUPLGA X C:AA A-AAACU 5293 AITrtI C A G 819 4997 UUCu.= Cu~iwXX3P X OA A03CX=t 5294 ALXP C CCGA 830 4998 USl.AGUJ C~aXU-LA X CCA AJtGUU 5295 CAGAT T AATM 831 4999 GCnXA~J CLtJADC2 X CGA AAJU 5296 .AAA A ACIACA 835 5000 Ga lJG CUGAUGA x aA AGUAa 5297 ACrqAAT T ACC 836 5001 Goctflf cumumG x cIA A~AGA 5298 CI'MAI A CA1dAt 862 5002 GCM= CUtXJGP X OSAA ACAJrI 5299 03ACG C CC~AMC 867 5003 txrtn CtGAUGA X OSA A03M 5300 TGlr= CAcM 896 5004 G3033 CtL3UA X CMA AUU33CA 5301 G1130= A CITIC= 906 5005 CACtnx= CUIMC7 X CMA AGC3C 5302 TGDC C AAGAAGIG 918 5006 OCUEJU CtLUA x aIA MOM= 5303 AAGI=~ C AAAGIt 945 5007 CC'C CUAxUi x alA .ACutr 5304 GAG T CAOM 946 5008 Utt'EOtJ CULILC; X 0:;A AAC03 5305 AAGflOI C AGGG 964 5009 CUM=n CtXGtXGi3 x alA AGOCA= 5306 GATCC C CAL 979 5010 cumc cumic; x aMA AILX 5307 ~ ACAT C CAGM 989 5011 tJGAUM Ctaun3 x aQA ACOJ 5308 AGr A 0CuAci 996 5012 ccJtmJ aucp x aIA AG03 5309 !=Acr c AcA 1014 5013 U03XJ CUCAUGAG x aA AG3 5310 GACT C AA03 1028 5014 C3A AM Xuc x A ACU 5311 CCACr A CCIG2I 1034 5015 UGA L2D2 X OMA ACAfl= 5312 CmIAi' C C3C~ 1040 5016 GCOGAMf CUGAUM X OMA AGO 5313 GTO= A CATCI= 1044 5017 AGAGS CUGAUMG x aA ALIXUAGM 5314 GOTr C 'iT03C 1046 5018 GCG CtLISAG X OMA AGAIXM 5315 CICA C QIGI 1070 5019 )ALfl= C~ J.uIG x aIA 2An33 5316 OC4Nr A CCCC= 1079 5020 CGN CUAUGG~ X CMA ACUO 5317 COM C GC3 1085 5021 0CO GAxUiAG X CCA GO 5318 G03 A C33C 1116 5022 AMC= CUMWXA X OGA AM=J~lX 5319 AAAACA T ATI3= 1117 5023 GAO CUMXI; X CKA AAUG=fl 5320 ACAA= A TG33= 1125 5024 AtLjtnr Cua~uGA x aA ALX;Cl 5321 A!1Gd' C GAAAA 1134 5025 AGLX ajt~u~n x a2A Ainjrnr 5322 GAAA C TG3 1158 5026 G0CGA cXuGAL3 x aA AG~kGO 5323 C30cr C TIAG 1160 5027 cooo axim X 03A GC 5324 CI~rt' T CAO 1.161 5028 AC3 CZUwJmG X 03A AAAG 5325 CIGiCr C A003 1170 5029 G0an aUGX2G X C1P m 5326 AGOO C GA7 1188 5030 AKAA ajGLPL3 X COA ADOMIM~ 5327 C3AA C COICI 1193 5031 C03A axxt=c x a2A AG3 5328 CAI ' T CrICC= 1194 5032 ULXnA CL13ALIMG X ONA AA033 5329 AIX C TItt~ 1196 5033 GAcW QiJPLA x aA AGAA= 5330 CCCCIt T C~CCG7 1197 5034 A~) axpomG x aA AAGAA 5331 i'COM= C C~COCr 1204 5035 GAIn= CL;IA X OMA AC03C 5332 rTCC0:p C ITGC 1212 5036 OOa UAXPMXG X CMA AILXL3 5333 CIC7T C AC3AC 1226 5037 GPXMCEADM X 03A ACACCUG 5334 CCG C CCG 1233 5038 GLI= CUGAU=~ X CM AOA 5335 ~ICC r A Crti= 1239 5039 LICBMCGX2XG X OA 00 5336 Cnkor C ACl 1256 5040 u~=axux; x aM ACG 5337 aP3 T CMU=I 1257 5041 LTGGCC L3AI X OMA AACAl 5338 GAMIT C GrOIMA 1263 5042 oc =axwxzG x CmA AamcA 5339 TIr1MI C AA3 WO 00/61729 PCT/USOO/09721 Table V. Hammerhe, ±'ibozymes to EAR3/COUP-TF- 1 115 1.280 5043 GC3C~ UCt~AD.In X OSA AGACG 5340 XCQIGr C 1282 5044 CAGThZ CLIGALLMG X CMA AGG 5341 AiGiGr A EG iti 1304 5045 C0CCG CX1AUCP X CMA A03 5342 GOO T GMM 1331 5046 AC==l~ CtrXAG X 03A AG3CAItJ 5343 GCAc C GCCC= 1340 5047 GOL033A CUADM X CMA ACL=t 5344 MO= CO 1353 5048 A~o= cusA~rnAG x a~A AcgX 5345 (ACCO= C GlJI r 1361 5049 GOUCAM, CAnLIr.G X 03AA AGCCC 5346 CG70= T CACM 1362 5050 Umr3UA CMAMAG x a:A AJOM 5-347 GImtrr c Azw 1374 5051 AAGAUO CUADMG X CA AM=fl 5348 GACAA C rCrr 1380 5052 UMXXAA CGaLIGA X CMA AXXXU 5349 A~TCO C TICA~ 1382 5053 CtU.tMf MAL~I= X 03AA A 53-50 ==.W T C=; 1383 5054 tJGaEtn CxrtTV= X OA AGAU3 5351 03CAT C CAGAC 1404 5055 A003 CGAMA x a:A AUEL= 5352 CAAA C AGO= 1413 5056 tt!GLCj3 CUCAMG X CGA AG03J 5353 -AG3 A CAI= 1419 5057 GCGM CUMDC; X CM ACOLII1AG 5354 CMCA1' C GACCAW 1424 5058 ACU COMLMG X CMA AGOM 5355 CUICCA' C AGOM 1433 5059 GCAxGnn CLILM X CSAAU3U 5356 AGCAr A CAGC 1443 5060 ALXXI= UGAGA X 03A AG3UG 5357 AGI=r C AAAG=. 1452 5061 AAADCA cuflAI;G x aA AU33=J 5358 AAG= C G00=~I' 1460 5062 MAxC=~ CUtMG~ X QMA ACD 5359 OG"10-r T CA3 1461 5063 LLMA= CM~nA X 03A AACLAC 5360 GIOICrr C A7IM 1466 5064 AGOO CUGUiP X OM CU~ 5361 GriCA= C AGAr 1484 5065 cooc cumxw x aA ACG 5362 -70Ic= c 070 1500 5066 Axinn CLGUM:G X COA MGM=X 5363 GCCAA C GA~kr 1520 5067 COCA= CaMXW~ X MA ACUUf7. 5364 GGGAr C GG 1541 5068 UCU CUALXM X CAIA ALCUCI 5365 MAA A C7IGA 1556 5069 Q2UXX CXGLXM3 X CGA 14LtOE 5366 GAGC= A CCCAC 1576 5070 tUU3= aLXK2 X CI A033= 5367 CtAGr T TIGGCA 1577 5071 GrX]3Z CLK2 X COAA A)~ fl 5368 CAGrr T T03AAW 1578 5072 AGEX= CUAMAGn X CA AAC 5369 AGrrr T G3CA~CI 1604 5073 LUt M aUM)M X CM MX 5370 ACir= C G==M 1619 5074 m= cuum x cA Acc 5371 CAC C CIO=~ 1622 5075 umom cm x a:AAMA 5372 Ui7iRi C C70I= 1625 50Y76- MUMMn aUGMzxA X 03A PDAG 5373 G1WIZ= C CGC 1629. 5077 t~aICM CUGAUM X CMA A02 5374 ItC~T= C A73G 1632 50Y78 AGrJ CLIGAuX2 X OA AGACOG 5375 'ICI3T C GACA 1641 5079 ACAAA QCLU X OA AGCUE 5376 GcGCr C Tr=~ 1643 5080 GGACGAG LIGU~XM X CGA NAG 5377 GCAGr T CI'IC= 1644 5081 C3kCA CaXIAuG X OGAAG 5378 CAW=r C TIMI, 1646 5082 A3A axLIMU X COA AGAG 5379 GI7rC T CXiT-TI'.r 1647 5083 AACM UArL3A X K 1 AAMAAGA 5380 C7Cr=trI C G70=T 1650 5084 ACA AxG C70M X 03A A PA 5381 TMtTI= C 0ITI 1654 5085 Aaag= xULM X :A ACG~ 5382 'IMIUM T 70i3M= 1655 5086 UACC= xUAM X A MOO 5383 03ICI' T GM 1659 5087 GUXAm cuo; x a3AAMA 5384 ulIuIj A QAA C 1663 5088- Gx333= xUMA X~ 03AAXM 5385 IGIG A AAC= 1674 5089X aMUutr Xui 0x M N~j 5386 AL'CCT C AA=I WO 00/61729 PCT/USOO/09721 Table V. Hammerhea- -abozymes to EAR3/COUP-TF-1 116 1681 5090 GC33AA. CLAL13G X CGA .PGXjutjA 5387 TooAr c Tu 1683 5091. tY03a3GA CTLflA X CMA PCPGJUU 5388 GAAACIC C AITC~k 1686 5092 ALAU= C XPLXW X OSA AMAGAGU~ 5389 AZIC=I C C0 TP 1693 5093 CAUAC CtX?4fl X 03A AM= 5390 TCGCA A TGTLi= 1697 5094 CAACG CUC49)M X COAA A[AUALM 5391 OGAT!Ir T ACIG'=i 1698 5095 CCGAA CEIMU X CMA AACtUAU 5392 GArT rr A III 1703 5096 tJGtt= CMAMA X OA ACGUA 5393 GIT9CIG C TGIAGC 1715 5097 GCCAGLG CtLrI X OMIA AcOXL 5394 GAGCr T CC 1716 5098 GOCCjU CtLr-AIA X CMA AAGCLU 5395 AL3C rr C AACI=fl 1726 5099 cSACAj CUflAGG X CMA AGCCGJ 5396 ACI0= T ACT 1727 5100 MGM=~ CUMMAG x aA AAOCA 5397 CITG3= A CAM= 1733 5101 AL133AMf CLAIA X O:A ACAUGUA 5398 'TAAI C CACC~ 1737 5102 GCALr. CLIGAUSAG x aAA AMOY=~ 5399 A~TI7 T C CAGI=I 1745 5103 AGGMtM CIAxLIMG X CA AGa 59400 CCAG r C Cn-a 1748 5104 CAA= CIALIGA X COAA AGMCA 5401 GIICT A @LtTI= 1754 5105 A1AGC= cuA~~ x aA AGUCA 5402 Ci9ccr T G330IT 1762 5106 CAMMM CUAL- X CM A03 5403 E33= T COIG' 1763 5107 GC03 CPVC7 X CMA AAO 5404 G330 C CACCI 1777 5108 ULM=3 CtXAUGA X OMA A03= 5405 ICCT C C~W. 1783 5109 tnz.tt CtmIXP x cA AG33~ 5406 GfttCCI A G; rIA 1790 5110 GOLX= USAUGAG X CGA AG=XM 5407 TMCL C AGU 1816 5111 C33CLIL LIt20 X CMA AGUCtUU 5408 ~ CAAX C CAA 1910 512.2 LtrOZxn CUAUG X CCA AIfLTXL 5409 CAMAM A MAM 1915 5113 GUG CAnVIXP X CMA AI~L= 5410 AI~Aa C Ca;G= 1922 51.14 AM=tJ CUA1A X OMA A~X 5411 'TC03T A CAA 1945 513.5 ttttUAAA UA~LUpG X 03A AUCE 5412 AGAGCr C 7rrnkGC 1947 5116 GAM.OA CGAUWZ X CIA AGL E 5413 GAAC~TCT T TnU= 1948 5117 MAU=LC CULIM X OMA AALG= 5414 AGfACI=I T TAGa 1949 5118 CICP CIGxUGL X O:A AAWAGU 5415 GAC1T T AGk 1950 5119 UCLIA! Ct7ALt2 X COA AAAGGJ 5416 ACItI'm r A GGAI G 1955 522 ACAIflJ CUALIGY X OA AtOEAA 5417 TI'1GGAT C AGAT'i 1960 5121 UOMO~k CULXGA X OA AUinxAU 5418 GACAA C 7GGAC 1972 5122 UCU CUAUtxA X CGA A~a]G 541-9 GAGmr T OM 2009 5123 Aahmmaxwxm x~I am ~Am=X 5420 AAAC T G7G7=I~ 2014 52.24 ACLrPACA, CXULXPG X CA AXACApM 5421 CrIGI= C iTG7C r 2018 5125 tnUACC CUALIC; X COACG 5422 GIItI= C TG7GA 2042 5126 trtmnL CU"39-PL X COA AUI~LXIJM 542 AAACAAT T O~A~jG 2064 5127 UMM~uA CUAUMG X COA AWCUCD 5424 ~ IA I'AA T TnA3AA 2065 5128 ULTJ(JXIA CLIGAtN X COA AAWMIM 5425 IGGA~ T V AM UAA 2066 5129 GUtLIMM CUGAUMG K CCAA AAAUEX=E 5426 GAGATI'r T AAMAAW 2067 5130 ImXXtiU CLIGA K CA AAAAtXJrJ 5427 AAATITr A AIAAAAOM 2070 5131 UUtnU CL~XPL2 X CMA ALXAAAU 5428 ATINT~ A AAAPAGA 2086 5132 PLM KUAA X PA AGUXX= 5429 AGAA~ A A103= 2095 5133 ANIJC= CLUM= K C MA AG7= 5430 ATCP T C~G 2096 5134 A)AU J CU3AMG K OA AAGO= 5431 IGCT= C CA==T 2103 5135 aM a=UXW X OMA AXX 5432 It'C. T V==I~I 2104 5136 UC~kn a)MLIMG X CA AAUtCXfl 5433 M~AA= T ATIU1rO~ WO 00/61729 PCT/USO0109721 Table V. Harrnerhe . -bozymes to EAR3/COUP-TF- 1 117 2105 5137 GXCA C XAIflG X CrA AAALttf 5434 CAGGArr A TIG'1= 2107 5138 CtIC CtX.A,'Z X O:A AIUAAUC 5435 GGT T GIMACM 2124 5139 ACGALI Ct)A[Y3 X CGA AULCAC 5436 ATGI= A TAwr 2126 5140 GUCGA CIMIG~ X COAA AILIOC 5437 CIGATA A TICIM 2128 5141 CUGl1CAG CLGUM X~ K G.A AULII 5438 GGIAT T C7IMO 2129 5142 CtG~kC CUta X CA AAIIAI 5439 GUM= C TGDCG 2133 5143 UGXU 3 CtLrAt7C; X CMA ACGA~ 5440 ThAI= A CAGAZ 2148 5144 CACUEX CMA=I~ X CGA AILM=~f 5441 CA 'A A EMI= 2168 5145 UXtt M CU X CXMA AGCU 5442 'Ir3A=L~ A IMAGAA 2172 5146 tfllJEt CIM X CMA ACUA3 5443 cr=Mr A GAAAAC 2195 5147 MfAAMIC CtMAtGA X CMA AMflU= 5444 CIUACAT T G~T= 2198 5148 AAALGAAfl MAnir G X CMA Afl3E 5445 AAI'I= T 'rATr 2199 5149 AAAUGAA CUGAUMG X CIAA ACAAULJ 5446 AC'AT A TIC.Trr 2201 5150 .ACAAAAfLU CUGAUMCG X 03A ~ALMCAJ 5447 ALITM=I~ T CA.TrrII 2202 5151 tUAAAA CaXIMA X C:A AAM~A 5448 =Ir=T C AT I= 2205 5152 UtUtMC.A CtIX X OMA ADM1AA 5449 TInTI= T MUM~A 2206 5153 AIXtJUEM MrAU X OA A~ALI 5450 TATICATr T IUI7AAA' 2207 5154 MXIJW CL99P X COA AAAGAJ 5451 ATICATrr T GAAA~k 2210 5155 t1WIUU OtLI X QOAA A.AAAfl 5452 CATrI'= A AAAI 2215 5156 AGCLIA CUPLUA X CGA .AIXXMM 5453 IAAAT A C]~TAG 2218 5157 AVAGA CGAIG X C:PA AGIAEXJ -9454 AAAT= A GICTn 2221 5158 AAAAflAAA CLGUA X CCA ALIPaPI 5455 ATA=~ C TIrI' 2223 5159 UGAAAUA, CLX;VIS; X CA AGCA5456 AMM= T TATr=I 2224 5160 AtXMAAAU COIXMs X CA AAGAUA 5457 CnItG r T ATrITA 2225 5161 AAMAA. MIMI=~ X COA AAAGAPM 59458 MGirr A '~TI.T 2227 5162 AAAUGAA CUM=~ X CA AUAAA 5459 Gt'ITMT T TICAIT 2228 5163 AAAAAGA CXLIXUGA X C~A AAAG 5460 TWrr=I T ~TCAT= 2229 5164 AAAAAALI aUGXM X CCA AAAtPAW 5461 CITrI= T CATrI 2230 5165 C.AAAAAU CU M X OM AAAUPA 5462 TI'TIT C IdTIrrIG 2233 5166 UEPCAAA a03MiG X CA L"I4AAAEJ 5463 MTrr=. T TII~TAA 2234 5167 UXAMAA CUAUIxp X COA AALINUAA 5464 TrI'IlT T TrIGIMM 2235 5168 tJUtIA axGKtx= X CCA AAXGAA 5465 'ITIC r T 71IAAA 2236 5169 AfXXZ MGM= X C3A AAXUA 5466 TI~~iTr T TGTAAAT 2237 5170 AALXL XW OU x : AAAAAGA 5467 'ITTrr T G7AAAET 2240 5171 LT-MAAUIJ CCAUGAG X CGA ACAAAAA 5468 7rIr A AAATTMA 2245 5172 CGnIGU, CUADu K CMA AUIXX1k 5469 1IAAAT T TAAA=C 2246 5173 aCxx3= KUAU X A AIfLUtXP 5470 GnAA~r T AAC= 2247 5174 ACGAIGL CL~IM3A X CCA AAXXXX3. 5471 ThAAA=~ A APAdA= 2253 5175 GC1PLC CUGGIGA X CA AMAXPt~A 5472 MAI.T C GnkTG 2256 5176 UA3 axwxP):g X CCA 25CtP 7 5473 AAA A 'I0CA~ 2264 5177 LtXX)=X CtTMIM X CGA A00 5474 A~TGC A A~AAAA 2285 5178 UUEu CIMB=3 X COA AUUxflXflJ 5475 ACAGA T PA03GA 2286 5179 UUrJ= CEGN1IGP X CGA AAUflflG 5476 MAA= A G3AAA 2296 5180 G.AA= UG AG x M AU ULX=r 5477 G3AAAT A AM= 2301 5181 .AUMMA CLKX X CA ALIAM~X 5478 ATAACAT T I'IC2A 2302 5182 UUXUxM xUUM X A AXtXU~JW 5479 A TAAT T TCAA~ 2303 5183 UX = anWMG X CrA MWA. 5480 Thrr T CaAAA WO 00/61729 PCT/USOO/09721 Table V. HammnerheL. bozymes to EAR3/COUP-TF-1 2304 5184 a =~~Ut CU90GA X CMA AADUGL 5481 AAM=TII C CAAA'AA 2310 5185 LUMtIU CaXMr.A X 03A AUUMOAA 5482 TICCAMAT A ATU~A 2313 5186 UUMMA.~U CUC4UJOP X C:!A ALXMt~tLM 5483 CAAATAAT T A.TAAAAA 2314 5187 AUUME CMfAGA X CMA AAIJEIJUE 5484 AAATAA Tr A TAAAAAAT 2316 5188 C~AUUirxx CEJAIW X MAA AM~tU 5485 ATAATIAT A AAAAI= 2323 5189 CCNMA aflALUA X 03A AUUUUUEPR 5486 ThAAAAAT T GIIC! 2326 5190 ?ACvI CUCLA X 03A.A AC.AAUEXJ 5487 AAAATIGT C MGM=it~ 2333 5191 GAUICAM CflAG X CXIA ACCA~ W48 TCWIGIU C T M 2335 5192 LWJM CUAUGAG X CGA AGL1ACA 5489 CItI7It A TGM 2339 5193 Cv'qtDAC- CGAC; X CGA ACLMA 5490 GICdA= A WTCM= 2341 5194 CAAM CUOA X 03AA AUAC9AG 5491 CrAI= C 'ThU 2343 5195 A~ACAU CAUGAG X 03A AGALVY 5492 =T~Cr A TATC r 2345 51.96 AAACG CXWIX7 X CS, A AUGAA 5493 GrATWrAT A TCIGi= 2347 5197 ~ AA mum-AG x aMA AILIMIJ 5494 ATCATA C IT=i'~ 2351 5198 AALVCM CLX2DC; x aA ACAGAUIJ 5495 AAIM r T TI'I=Tr 2352 5199 AAAAC CUAUGA X CGA ACAGI 5496 ITIaIT T ~TI r 2353 5200 AAAAAAC CM20GA X 03A AACA= 5497 A7CIG=T T GDUrrr 2356 5201 GAAA)AAA CM20GAG X CSA ACAC 5 498 'IuiT'iur A TrITITI 2358 5202 CAGAAAA CUAM X CGA ALIPAAA 5499 7rI7=T T TITI1t1 2359 5203 CCA3AAAA CaxwGA X CC1A AAUACAPA 5500 TIGA T TrriE= 2360 5204 AMCAA CUP0,7 X OMA AAAUACAA 5501 7I=T T TIC=~ 2361 5205 IAAGA CMLIG X A AAAAIkak 5502 'I!;Tr T 71I=I 2362 5206 GACCG KUAU X A AAAAALW 5503 GfMT=T T 7CIt'ir 2363 5207 03AACCA CUAUIGA X OA AAAAAAUP. 5504 MT=TI T ci7ri= 2364 5208 UOA~ CIPXIkG X CGA AAAAAAAIJ 5505 ATrITrIT C TOM=~ 2369 5209 txnLXUt CU!MI2 X COA ACCGAA 5506 TIII= T CCAP~ 2370 5210 Cu~JtJ anamw. x Aiamcm 5507 TrCI7= C CAAA 2381 5211 UCCGP aUMIGA X CCA AULCU= 5508 AACAGT T I71MM 2382 5212 ACAAG CLICP X CO A1ALr-= 5509 ACCA T Ct'IT 2383 5213 AALA CXMWGP X MA AA 5510 O=L& c CM7=LI 2391 5214 L~WMVGLIGEM Xw K m ~AIM 5511 CIUI= T CIMA 2392 5215 Ur~aM CLXPOzA X 03A AACC5512 CI7I7.T C TATCMA 2394 5216 UUPL CUMUGxG X CA 1~AGAUC 5513 GIG.TX A TAvnU 2396 5217 AM2UMG CL2U2 X CA ALPnAALC 5514 GAITT A CnAkAT 2399 5218 AA)AALW CL~LM X CGA AGWG 5515 ItCrk A AM =rr 2402 5219 UCAAAW CUADGA X CMA ALXP=W 5516 ATL!~AT A ATITIA 2405 5220 ALULXAA CaGX2G~ X OA AtXCIXM 5517 CIATAA T TrI'IA 2406 5221 UUCAA w KUMA X GA AIX]Mt1R 5518 T~AATr T TIM=h 2407 5222 UtffUAPC1 aMVXMG X CMA AAALIM 5519 AATA=I T TG7AA 2408 5223 GUA=rzi CUMUG X CA AAAAMIAU 5520 ATA=I T GUMA 2412 5224 A3ULI GALKW~ x a:1'A AMAAAA 5521 ?TrIA A T.AI'r 2414 5225 CAJO CU2GtXGL X OA AUUX2).A 5522 TrIKA=~ A Ari= 2420 5226 aAtxVL C K;JA X GA AG03LIA 5523 ATLW= T RoICYL'r 2421 5227 UAGAG CU A K CAA A~AGOM 5524 TACrr T OI'It= 2425 5228 ALXMLDVG CuLIGAGA K aA AGAA 5525 CtITI~r T CrnkTAT 2426 5229 CAUJUA CUGAIGA X CGAA IARAA 5526 Ci IMI'Ir C TLAZ 2428 5230ALGA X~t~ CMAr AGLL _5527 TI~Ir T AMAA WO 00/61729 PCT/USOO/09721 Table V. Hammerht ~bozymes to EAR3ICO1JpTF~1 119 2429 5231 ACAUI CVGU)GxG X CGAA AAAM 5528 EiTttT A MAG;r 2431 5232 GCCUA CMUA X OMA ALMAAA 559 C't-AA~ 2443 5233 ACAA UAxUMx X 03AA A03MU 5530 CTMA A ATuriG 2445 5234 aC~AC CUUtJM X 03A AflOt 5531 AIM1M A 'iArI= 2449 5235 GCUCA aCnM x 5532 7003A= T GI= 2452 5236 ACDzc anUUIG X CEMA AMAMI 5533 IuriG r C GAO 2461 5237 ttTUAGL CMM X OMA AOAG= 5534 GAO T CrICAG 2462 5238 LXfXXA aX-Al X CGA AACt!J 5535 AGOrr C T1CAA 2464 5239 AAIXtU CTMIXG X CA ACACG 5536 GCIGrT= T CAGA~ 2465 5240 LWL~rX=U CtaM~ AAGAA537 airtr cAAGm 2472 5241 tAXXJ allVJM X CMA AUXJE 5538 IWAAM T AAAAd'I 2473 5242 UXJCWWi CLIMUMG X CG AKYImEIG 5539 MAA= A AAAT71GAA 2478 5243 txtMCrx axaumG x aPA AuiJUmmX 5540 -ATnAAXT T G@AGIMA 2490 5244 LXXtnXXA CIArIMG~ X C2A ALUXXrAC 5541 GGAAA T TA~AAA 2491 5245 tLxxxmxyL CL2X); X 031A AAXXXXC 5542 IGAAAAT T AAACAAA 2492 5246 tuxxmv aJmuma x aPA AAAIuxur 5543 - -AAPdT A AACAAAA 2502 5247 AAMXXUWM CUMIXML X CM5A, AUUXirin 5544 ACAAAAT A AAT Where "XC' represents stem II region of a 1{H ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20: 3252). The length of stem II may be 2:2 base-pairs.

WO 00/61729 PCTIUSOO/09721 Table VI. Hammerhk. ibozymes to IRF-2 ________120 SUE seq~. Substrate Z.. ~. __ __ __ _ __ __ __ __ __ __ _ I.D. NO 13 5545 CflAAAUM. CUGNEX2 X CGA AGCCC9Xi 5967 c DCu U tUCAL(X 14 5546 UOMAEInGfl I X x aA A~c~c 5-968 ?ACOOUU U CXUXr 15 5547 -AIJ3MAAI CL13AUGA X OMA AA13 5969 C333M c ALutjc= is 5548 @AAL~ C!LUUg X CGA AUAA3 5970 crtXM~ U LICAUr 19 5549 UGAA1A1XG CLUr- X CUDA ANIGAA 5971 CUXX7LM U CuCAit= 20 5550 CXAkAm aCtuiGA X CMA AAK1MM 5972 UtXX= C auxJE 24 5551 CaflXx CUxwjm X CMA AUOMAAfl 5973 AEXXXAU U tUOCA 25 5552 cflhUxz CEX)GP X CMA AAOMM 5974 tUXIXJA U CAACC 26 5553 c3Mnnj CGUMG X CMA AAAIXAA 5975 LX)XJ C ACCA 36 5554 AU=n CUGXJGXG X CMA AaXM 5976 =C-= A GACI 45 5555 aVM CVMUGA X 03NA AGUX 5977 GOW MU Au %CUM 46 5556 GOn aautm x amA AAGU=f 5978 CAACAU A tUACLX 48 5557 CCMA CLUUMG X C3A AMA=l 5979 AOCUIA A CttX 52 5558 AAICt araunxc X CM GUA 5980 ULMLMJ U G0ATJU 60 5559 AIAL aXWXL7G X OM AJO= 5981 MOM=~A U a.WgJrj 63 5560 GcMc, arjzric x amA AkaxX 5982 GMX A UU3A 65 5561 AMA cta)MLG X C3A AMAW~ 5983 AAX;M U Map=fl 69 5562 UMXA= MUGAG X OMA AX.IM 5984 (IU=l~ A GOMX1?W 146 5563 ULXzPGn aiUA X CA AMU= 5985 G;CM A A~AC03 -151 5564 tOMnix CAUMGX~ X C3A AGxxwr 5986 GUMAA C CACAG 161 5565 A~o axmlxw. X COA ALK U= 5987 ACCGU C C0033j 170 5566 -ACM CuAU,-4 x amA AGC 5988 C0333C C AIflMJ -179 5567 LtnLV=n CAUGiAGc X CA AGCCair 5989 AGUO U AAAA~ 180 5568 utn=Jn a~zx=c x aA A~Ga)3 5990 AGLUJ0 A ACAGA 197 5569 ALKLMAA aMUC; X COA ALUMMfU 5991 AGAXW U urXXICA 198 5570 GNMIMA anqzGp X CGAAU 5992 AGOCA U MtIrA 199 5571 CGMIL ~a aJmLmG X CC AAAT~UX 5993 GAAG;XJ U LICAAIfl 200 5572 GOL= CLIML2 X MA AAAAU 5994 AAGJtXX U CAAU 201 5573 G33:;'= CLINVj X CMA AAAAAIU 5995 .AIIXXIJ C AGX 206 5574 ADOM;Gm acmvzm X a3AAUS 5996 tUxxL~vw C CZCtLGMl 225 5575 cmwmic~nz x COAAOO 5997 ALO A GACAUGM 260 5576 MXUPAA CLxGAUGG X COAAMO 5998 (GLT~JOJ C XWMPA 262 5577 G=XXMl~ WaLXPLG X CMIA ALPI 5999 ACLauJ U UWAPAA 263 5578 cmr anvwmG x amA~G 6000 C=n.XJ U AGAAP= 264 5579 C~aXXI CUUM X CC AAGW 6001 C~AnmLU A GAAC 278 5580 calmim aimoGxG X CCA AMU= 6002 C 3= C alXPOM~ 282 5581 axximi; Cum X CM MN 6003 CAUD A CAAG 294 5582 LM1jj CLIWMAG X 03AAaE 6004 GAAAGWf C AACG 305 5583 ajMW= xUMP X GAA I 6005 CikG:W A GIPAUAAC 309 5584 AUMU LUVCa X 0CA AW 6006 CG72MV A ACCEl 318 5585 Luxxx axmx X CA AMO) 6007 ACfL C CCAM 339 5586 GMCM mx x cm Auumocr 6008 AUM U ICGV 340 5587 co xmGA X CA AAIX= 6009 GOOAMX U CAAOX 341 5588 G030= aLIXPl X COA AL 6010 =AMX C AG)G 37 5589 atwxptM xLGUA XA uAIm 6011 =OMM~ U ca) WO 00/61729 PCT/USOO/09721 Table VI. Hammerhea,. L~ibozymes to IRF-2 ____ ___ ____ ___121 358 5590 CAOCA CUIU X OSA AAIXCIM 6012 auAAUU c aximn 361 5591 UAM;Gx armAG x aA LfAostfl 6013 GATJt U GCrAM~t 369 5592 UtUtLIAA CtX-49YGG X CSA AL 6014 tfltUCAl A MUMM~A 371 5593 AM=t~J CXMAUMG X COA ALMG 6-015 C=CUMGXU~ U c~ 380 5594 UtUirDCt CtX;UIG) X CSA ALXfl= 6016 GAGAG C AAA 387 5595 UAU3CUU CUSAMOL X CGA AxUCrTJ:P 6017 tCAPA= A AAAGIPM 395 5596 7EXutfl mnJ C Ix~ X A AmLflxilJ 6018 AAAAGCAU A AAMAA 408 5597 -G)AG a)UA X CCPA ALXX= 6019 AAGGAAAU A AtUfL= 415 5598 AGC~ CUMMA X CX91A AiGXi 6020 UAALK3U U CAGtU 416 5599 twGcmJ CtLIGAG X C3AA AAGOAU 6021 AAXDCV( C AGIL 422 5600 ALXXg~ CUEAMAG X COA ACOUNA 6022 tUAG C UAOM 424 5601 GMX CLGALM X OMA AGAC 6023 CAG:X A C03AtD 440 5602 aOULIM QC[flAj X CMA AG337 6024 aL100u A UCGA 442 5603 Gjtnj CLIflMti X CMA A10 6025 GCt~t= C AMA=A 453 5604 tJLXXTJM C039)A X OMA AGOXJ 6026 AAIOU U CLMAGAA 454 5605 CULrCM~ CtLIAUM X 03A AAK3033J 6027 AC0U C tLMAA 456 5606 LLrtULXnj CUMOG X OMA AGAGC 6028 G3CCEu A AGAC 4-97 5607 -ALDGT)O CLIML&xA X CMA ACUEXr 6029 GAAJ U AAPX2U 498 5608 GUnM= CLGLM X COA AAUUXflJ 6030 ACAAAGUU A AOCirA 506 5609 tL'CEntOu CLxGALU X COA AIXGU 6031 AICAfl C AACAG 521 5610 cGiLar CLiIGAUA X OCA PALGMxr 6032 GACCG U GAGxr 526 56.1 OXAGnA CMAUGG X 03A ACCAC 6033 AGXGG C AI=X 529 5612 GCOAA CLIGIGAG X OA ADM= 6034 UGAGULI7J C LXttXX 531 5613 AAKCCCM CLUW X CMA AGD 6035 ALICALIU C 1333M 539 5614 CCALXM an139X;G X CA AGO 6036 C~U3U U ~AAM 540 5615 LtCXLtM axw.GA X CMA AAOC 6037 Lt3333= A GLMALG 543 5616 WYMCCAn CL~XLIM X CGA ACMG 6038 GOCXMW A A3G~ 551 5617 ~AI9CU CLEXU)MG X OA LIMMJ 6039 AAEX3gJ A AGUlAI=l 558 5618 AGAGAA aLXPLM X CCA AMACUR 6040 LVAGfLK C JUtE~r-J 560 5619 MAGG CU3ML:9 X COA AGUCC 6041 AGXP U tLrCCCG 561 5620 CLAGLA CULM X OA AAGAUCC 6042 GUGAUCU)U U CUCL 562 5621 ACU .~ azLIjAL X C3A AAPLWMA 6043 tUtruw C 1ox~~ 564 5622 AILXA CIMM31W X COA AAA 6044 Aulxxtcu C CMGawJ 571 5623 GWXX aMWxPL X 03A ACA~ 6045 =M~ A U303= 578 5624 G)Aixo;G amukG~ x aA Acm 6046 tw.3J C CE~XP= 585 5625 twALPO C1AIMG X CGA AGCG; 6047 ttICCLAU U CAACMM 586 5626 txw.An CLIxGA X CrA AAJCa 6048 0=2=W C AALWA 591 5627 ALrXXXXIA aCLA X CA AGXIMW 6049 CCAxLU A MAAA 593 5628 UCALUM CriMz s X CM LOT~ 6050 Ut-AU A AAAAAUGP. 609 5629 CA00CCIAX X 03A AUCM= 6051 AAGUC;T A GLPD= 612 5630 MUM= CMUMIX X 03A ACVC 6052 L13GAUAGL A C33LIMW~ 623 5631 ACAUUCLIGG X CMA AEGUt7AC 6053 GUGPAAMf C APAG1fl 626 5632 C axwxAA xL,4VM X GA AUGLU 6054 AACALIJ A GUXUP03 629 5633 UMU LXUM X CA ALafl 6055 AtUPAUA U GLPDM 632 5634 -ALG CUL3M X CMA ACUU 6056 AU~mmJ A GGCAU 640 5635 CUCLGAIM x aA ALU0 60597 AGOCJ C ~XX 645 5636 G axXir xMUA X CA A3AW 6058 AGic= C WO 00/61729 PCT/USOO/09721 Table VI. Hamimerhe- .<ibozymes to IR.F-2 S122 659 5637 XfAM=x a~MA X CIAA -fL3LX73 6059 AGAAA U GAAU: 666 5638 AArtUU CUMiGA X C3A AIU=XEA 6060 Ut3jc 674 5639 U03GUMC CL13AIGA X CGA ALtUUM 6061 POO~~ U GCXCLA 577 5640 c5REj ai w x cXa ACaAI=r 6062 CGAiALAW C ACAAC 684 5641 GUCLnU30 fAUG CA EtLZIRXM 6063 r uC 695 5642 AUUM CUGUi; X C1MA AfLtSUM 6064. cu~ u ufltAAGJ 696 5--643 A~aXMC CU- X CGA AAUfllf 6065 -CAGACAUUt U GCAAGOU -704 5644 ACCLICLMc CLUUI X CMA ACUU03C 6066 tfGj U GLr.W 707 5645 CLXAIXTC CUGAG X .CAA AAAEX 667 -CAjtn A G~n 740 5646 CUAE2U CLGUGAG X CCA AC030= 6068 CAOO C AOXAG 755 5647 AG03 CLIMLr-7; X 03A AGrt03CJ 6069 AGaOU C UACCCtCj 757 5648 W.AM axUUxn X O:A AM~aM 6070 -Cw-mn A axn= 762 5649 GALLTuIO CLC43A X OMA A0OA 6071 UtCtUA C U3=kGt]n 770 5650- A3mmk ctLuvlmG x (cA AUCL136072 Cuxj3cGn C tr=C= 772 5651 LACA033 CUAxiGxx X OCAGUCG 60-73 -GCP C CCO=n 781 5652 CLGGA CtGAIM X A ACAC333 60-74 -CXZCflJ C UJOCCIf 783 5653- tU3AU ax;MA X OGA AGCA3 6075 -axu u CCUAUOCA 784 5654 Cuu; aCuGA x 03A AAGCAC 6076 MUGU= cJ CLPIG 787 5655 umuxxA axaLxGA X OMA Aa~ 6077 GLLTutX A UMAGAA 810 5656- G3CA CAUGAG X CCAAU 6078 03ALUWf A MGM= 867 5657 GCtLXXA (XJUGAG X CCA AICttl 60-79 --- AO; A UUEAAM 869 56 5 8 utnt'wz CUMMA x aA ALWUtU 6080- AkAU U GGOA 883 5659 -Ui~~ Xv~w x :A ACUG=x 6081 ~aWOW~ A CxtrG 887 5660 miu cmqmw x a~Aau 6082 CAGLIA C GACI 903 5-661 cGmo~x anvnA x cc;A Am-683 U333GAC C GY3tr 910 5662 GCGS CL3JT X CMA AGCO 6084 tLCM= CLMCC03 913 5663 GmcXi an.u; x E-~iw 6085 AGL32= A CCLmnX 934 5664 tnACGAj CUGAUG X COA A0Ca 6086 (CiU3u C CULtGM~ 937 5665 AuomccxiA x coA Amu 6087 cOU= U MUM 938 5666 GAApUM CUAx w M X CI:A AAC 6088 GCOU j C G UCCX x r 941 5-667 LUMPO CUMV.-A X C3A ACAG 6089 trtum C ACMM 945 5668 -ULXUJ= aLIMM X COA AGUMC 6090 U33ICA U C~M 946 5669 GLUM CLGIA XaCA A~AGU 6091q- -iauc c avmAw 962 5670 GUGPC CUM X CMA 6092 00GA C CAGI= 968 5671 txxwoN= cumum x aP CLOg 6093 Ca~rM C ALXA 974 5672 trCCuCE CUMiGZ X CCAAXM 6094 UCCA~U C AAGOC 990 5673 AGMC C13JGA X CMA AI~LTJ 6095 AGAOCAM C a33uO 999 5674 OCLIODE CIMLrM X 03AMOS 6096 COMO U CAM 1000 5675 Aaaxm CLI930A X 03AAG0 6097 MlU= A CACGE _1009 5676 G330A CUGAUM x aA AG=MI 6098 CACN C CU33X 1020 5677 GCXUAIA CLI,-MM X CMA A033C 6099 GGuO U UJXAM 1021 5678 G~aX CUGAUG X CMA AA3M 6100 GCxy U" A~c 1022 5679 AG~aM xUV2 X M AAM 6101 CCOO= U CAGCE 1023 5680 GA twx xL,;JA X :A AAAG 6102 CCuuuu C AAGAC= 1031 5681 GAA=CLMW X OA m 6103 ~CAAP C COOCUUxr 1037 5682 GAGAkCUMIxp X OA A33 6104 CL~nU U LrX7t 1038 5683 GMNGcuArwaA X K A332 6105 tMO= U CaXC= WO 00/61729 PCT/USOO/09721 Table VI. Hammerhe. ibozymes to IRF-2 123 1039 5684 UaNC3A CVMAIM X CCPA AAG03 6106 ~ ~ wCuxr 1041 5685 cA'3A CLXXK x CmA AGA6107 ccctxxu UL)A 1042 5686 tX6iI j CtJ-G x 35.A AAmD 6108 CCULXxruu c ct~xxG 1045 5687 GOODrA4M cuMrn X CMA AGACA 6109 66E6Erc curA 1060 5688 Tuoua CuLXP X CGA L 6110 CCCGM C aCa 1071 5689 Gtt)O= aJL) X CCA 61~a 11 GCGCC C G3CA 1100 5690 tjtrnXW CUif X CCA AOOC03 6112 GCAG C AL)OVA 1103 5691 C-tX5tu arX;Uig X OGA AIM U 6- 113 xAoouc C AAWAAAC2 1114 5692 utn-IAij aj-)A X XMA AIUJUU= 61.14 -CAAAcIJ C GMU 11.19 5693 CU'G arEM x (JA Aiuifl 6115 CAIOirWn A tUC 1121 5694 GCxrUO= UIAMOGn X 0CAA AM001 6116 UCOL C ACCA3 1136 5695 raUu axaunw x ma -an 6117 GCCCO= C AAGAG 1146 -5696 -Z ctxwnG x MA AG 6118 AkGCUJ U AtGflI 1147 5697 OkAG CUmx;G x aA AArXTX 6119 GAfljU A .'Gr~tatI 1153 5 698 -Ma acu mxpr x ccA AG~iAA 6120 LIMAGu C tU-XXU 1159 5699 AcCG3 cuauxw x a AaxAGG 6121 CtLflMALU C UM0331 1161 5700 -CA03. aimWm X CMA A~GX) 6122 a.inj C ma 1171 5701 Gcc=A axuGr x aA AcA 6123 G03U3jJ U GULX333 1174 5702 GAG= CMUMifl X OMA ?AAA 6124 GUGOUXnji U G33CLI -1181 5703 AACCA cLUAUG~r x cA Aaam 6125 Lu7333U U CUt33= 1182 5704 AAACCIA axw-=x~ X %A AAc~ 6126 ' U033C C Ut133= 1184 5705 AcAAC aj~m3z7 x crA AGA 6127 GOO!LU U G~urm 1189 5706 ACAAM~ aititw X 03AAOa 6128 ttVLl3= U TfOLJUEX -1190 570T7 AAaAA)C amuGA x amAm A 6129 CL.JO= U G LTXXUM -1193 5708 AAC CLGAM X COA ACA10 6130 GC~UU=n U t m 1194 5709 AAPAC amv)GAG x a AAcAPLm 6131 GJrCLjU U UaLnJCU 1195 5710 avz~ Ctpim X 03A AAACAAAG 6132 CLXUXXW U CGLX]3= 1198 571-1 AAC aX~nk X CMA ~AAMC 6133 tflrJ=tl U GJEXfXJ 1201 5712 -UMAA axxx2 X CMA AaACAA 6134 LXmRtnJ U UalUHOM 1202 5713 ALMCA~ an~m X CMA AAAA 6135 rLTJ~ULX U GLXtflWI 1205 5714 -AAAAEA CIAL X OCA AAAA 6136 UfL73UULJ uUPO=IXX 1206 5715 UA~kk axpum x a-A AmwCA 6137 U~~lJU UALXUY 1209 5716 AAAUAAAA. CUMA X CIMA ACACA 6138 ULJ3LXX3U A UXXP1J= 1211 5717 AAAAUA amOGAG~ x ap AuuAw 6139 GUmXX U L~hXUljU 1212 5718 AAAAAP C!JLGLO X CCA AAPL2AA 6140 LtfLflIOXJ U UAXTJ 1213 5719 AAmAU axxLuM x aNA AAAELLA 6141 tULXJ= U AMXXXnX~ 1214 .5720 GkAAAAAA almum x cr.A AA~~ 6142 tfLM~XXJ A MXXr 1216 5721 GAAAA COGUGAG X O ALAAAM 6143 tWXXUtLD U UULwrn= 1217 5722 AGLAA MaxwUM X CMA AAiAAAU 6144 ALXXXMX7 U UUX=n 1218 5723 GkAA axp2Wm X C3A AAMBAAA 6145 tXrXPLWJ U tJutEctc 1219 5724 ACMA CLXzm X CM AAUA 6146 LTJELWXX u tXuajL! 1220 5725 CAAA aUGMX2 X CIA AAAA 6147 tXMIXWtU U ia~XII 1221 5726 UCGAN CIML13A X CA AAAAAM 6148 LVIXXXWl U CLttEEXP. 122 5727 GLxMGAGN CIUGA X OA AAAAALI 6149 AUJEX C LXtXML 1224 5728 cGnrUcA, Cuj x a2 ~k-A 6150 IXXX3UEL C UCL13A 1226 5729 A==XA~ CM-W X CA 6151 tXtXtf C LGACA 1235 5730 =AA acuV-iM X CM ~n 6152 UGXCAU A UUULPG C WO 00/61729 PCT/USOO/09721 Table VT. Hammerh .(ibozymes to 1RF-2 124 1237 5731 ttUM atim; x c3AA AuMAG== 6153 ACAC=flUtX~ 1238 5732 UMtfltm cuomr.xG X CGAA AA& 6154 CACUU U UAAC 1239 5733 ALflnr uvGr x X ;AA AAAPJ 6155 t!fUU 1240 5734 GAUflnn CtMAG Y OSA AAALMM 6156 CC~LMUMr A GAAI 1248 5735 Luc~Tjt. oaAu2.A x C3AA Am==fYJ 6157 ~AGACA C UMG 1.250 5736 Uurxtc arfAUGAG X (MA AGUXmX= 6158 ACAADCJ A AaAAAA 1264 5737 cuur ctmuc.il X COA AUEJUEJ 6159 AAAtu U GAAAA 1271 5738 aLt % lL;XgA660UjC=j 1278 5739 cACCAU CUAM X OSA AUGLMMl~ n6161 tm@kAAU El Gux) 1282 5740 GNCA aLUMAG X OMA AX;A=x 6162 ACWXGAU U cxnLr 1290 5741 tUGKn anAG X 01L AaUGM 6163 tnar= C (:3A~uttk 12U96 57-42 AGLM CXU<LXG X CMA AXfl; 6164 GCCAACU C CAGUA= 1301 5743 GCiCAM COMM-M X CCAA AaXMW 6165 ACCCGJ A OC1M 1311 5744 ULMAGA CUAL7= X OA AW16 XMGU fj~~ 1312 5745 ax-~ c~~XIAAxtr 6167 TL13=U c tuaX.IAA 1314 5746 GAQjkA CUMUGA X MA At 668%tA Ctx 1316 5747 -CtMGLMp CUGALMX aA 6168 (Xfl=tt U A 1317 5748 Ct uqc; xt~ X A AANMA 6170 CuUTrra U AACLG 1318 5749 ttt~fl-cj ctuxp x o:A AAAPLmA 6171 ULICLIrUx A AL'UM 1322 5750 GMCGJX cuu X CCA AGUUAA 6172 CUtXALTJ C AGCIIC 1329 571 AGM axwUpr X CMA AG=UGA 6173 tXAG3ACt C CGCC= 1338 5752 nnLZ~c axMMAG X CMA AUMO=Tf 6174 CAOCA U GOMA 1342 5753 CAAM CL13UGA X ACOA 6175 -OAUXX3U A GA3m 1352 5754 G~UG CUGUMG X 03AMU 6176 AC)UGj U UanGAr 13593 5755 GCL)CLMG CLuGLIM X-CP AAP 6177 COLjIGE U CLGA 1354 5756 AG~x anvim x CCA AAAPDCC 6178 GXUjw C U;GA= 1356 5757 Gm= anumG x 0A AGMA 6179 GLIOUitf A GAGCL10 1370 5i758 -cmnQk c =UMa x OAITA 6180 tnn- t 1372 5759 ~~f~a r A~m 6181 U3xI1nh C UCCAM 1381 5760 MtnLI cax ):xG X O~A AG5CE 6182 CCCX3= A CDACUMT 1384 57-61 AL~UMMj CUQVxM X CA AGkG 6183 G33LUC c 0E 1388 5762 UrXPA= aicxG X 03A A]GA=Th 6184 tUACM C ALXAGUA 31393 5763 Qmr= axUVtM X CMA AtxIM 61E85-- -AuEXW U CAGA 1394 5764 -uMXj ax~ x cA Aa3= 6186 COWUM C AAGA 1427 57659 aM~c xuum X ap.AA AMU 618r7 tmnLG U GOU 1437 5766 a)OM=y aia x K Aom 6188 MUM=j C AAP30 1465 5767 tuirMj cu-Am x aA AGcs 6189 GGAU C AGA~ 1480 5768 GMIM= A~flx 690 ~ lA ~l~ 1490 5769 Axx=M anaL7GA X 'a .pGjtxkc 6191 tfLXAPaJ A G!fL3MW 1499 770 GW anvix~ XCa AuIxfP -61-92 Ga.WAI U WUM= 1500 5771 AGMA CLIMw X CGA AAiXG 6193 CGALUi u LnmXXIX 1501 5772 AAkm amuom x cm ~~ 6194 UGGAAUU U txLwxnx 1502 5773 CUA xn1M X XAAAI 6195 GGAUUWr U LUVIX= 1503 5774 ACLMCIM X aP AAAU 6196 GtXTU U tmT 1504 5775 aMAGA CUxW X A AAAAAAIIJ 6197, AAXJLXJ A UXI=fl 1506 576 U(OWamm x cm uuAA 6198 UUUXjtmn U IA 1507 5777 AU-AxC i xMAM X GAAAAA 6199 UJU~U C MflAD WO 00/61729 PCT/USOO/09721 Table VI. H-ammerhe .Thozymes to IRF-2 ________125 1509 5778 -- AuxxAr- axiuA x caA PLrA~luMA 6200 ULI.MaU= U arAAI 1516 5779 uuunic cxuG~r. x a:;A AuEcr-A 6201 UtfflIM A EMaUM 1520 5780 tnrtamm CtLIU X CGA ALaUWA 622G-i~~ 1524 5781 Ginx= anxurw x a; A Amc6203 GAAf f A 1534 5782 AMU=~r CUG~nA X 0: AGflGf 6204 GCAGCAJ A GCACUU 1542 5783 Cakct= aClUI; X 03ATAtLJU1 62-E05 -ACGC U GCxAc.' 1548 5784 CAAGC CtLAG XaCpA AaUG.A 6206 AUGtA~J C t~Xtutr 1553 5785 ~AGGLn: aUALUAG X CGA AGMGLU 6207 AGJCL= u axo=t 1554 5786 AArn9j= Ct~mx.- x CGA AA~o~c 6208 cGrtnuu C UOl2CA= 1562 5787 UMMAGAU J UXW. X 0C;A A2LIGM 6209 C3LX U ALLUAA 1563 5788 QcuLUAAG cumuak x aA maxmmI 6210 UOMt=t A ttXtWA 1565 5789 tGCUJUtA CUMMAG X CMA AMADO 6211 CACUF4 C UUAAGC~ 1567 5790 AGJOUU a)W X CMA AGLA 6212 OaXItAir U AAGC7' 1568 5791 AAfLG= T~~X~ 23 ~~ruAzx~ 1576 5792 -cu~wx= a]LM X CMA AaX= 6214 AAAL! U AAA 1577 5793 ctru.In axu,. X C3AA AAJU 6215 AAILTJE A aMEM 1583 5794 AGA03 CL.AM X CMA ALIUAA 6216 UtCAGJ A Go==ttT -1589 5795 AI7MCA CLUA1G X OMA AG=X 6217 ALDtU U CuLXLfl 1590 5796 GUA CMUU X OMA AAO 6218 tAGuu C ULtXX;= 1592 5797 AGAUCC axxr X OMA AGA 6219 GOCuXTru U GUM=x 1598 5798 t-.flGAGCA CU~nXZ X C3AA AUCA 6220 CUMUM~U C U~aTftJA 1600 5799 -GPXCUEM X MA ALUC 6221 tflfl-A=t U Gcn7-p 1604 5800 GLW-I atrIuGA x cmA A~m;A= 6222 Axu= C UMMAC -1606 5801 CLUE4G CfLGLM X C3A AGMA 6223 CUn~U3 A tCL!ONMG 1608 5802 txrCUMA axxiG X O:AANA 6224 LXDMUxW C tinom 1610 5803 tnntri aXKiXW X OM AGNIAM 6225 artwni= C ACACA -1621 5804 0339 a~E~; X C:AAJX 6226 AGCACW C AGA 1632 5805 GOMtLA Kum.xa am 6227 CA1.Ct U CEfLfLT 1633 5806 W330;a CtXmDG X MIA AAG33 6228 ~ACCO C UrnG 1635 5807 AMm CtIxm x a3A AuG 6229 CCCtru C t~c~cm -1643 5808 GM=CUUX2 X 03A AO 6230 CEXXU U CCAC 1644 5809 AG3=3' aCtWiA X CaA AXAI3M 6231 tGOOAM C tM= 1653 5810 MOA anM X CCAan 6232 cc= C UrttXI 1655 583.1 GUM axx X C3A PLnM 6233 CAJO C UJOCEP= 1657 5812 GO~r K~E)7 X IA XP 6234 GCfLnI U cam 1658 581w ~ p U03 W~ Kx c3AAi 6235 Czttvu C CEMU= 1661 5814 aM73G aXKXW X CMA AGX 6236 CXMIC=! A UtO 1663 5815 UOGA0 KL2BA X A AMOMIG 6237 -CMIO= C AIOC 1668 5816 u33=M axuw~r K aA Au 6238 UAUCAU C COX~ 1673 5817 u1J:P= ajaiz2G X 0A AUOZf 6239 CULKX=f c cmxI 1678 5818 U033;, axxg K CA L 6240 ALU C OZXr 1683 5819 a03m= xUOM X A ALtXXM 6241 CAUO= C CCU~ 1688 5820 a03M= CLGAg X A AL13MM 6242 CAIC C CMXC 1693 5821 coom a~xzu2 X 03A AMOMM 6243 CAUO= C CAL 1698 5822 AA= aUMLP X CZA AEU3:P 6244 CA00 C C0t3 1704 -- 5823 UN3AAA txxx;; x cA A~f 6245 AIUOX C ULXX3 1706 5824 AGaM aM~nA K CAMG 6246 CLtra=u UECCLPaj WO 00/61729 PCT/USO0109721 Table VI. Hammnerhe-. - ibozymes to IRF-2 ____ ____ ____ ___126 1707 5825 AAUX3p- cax~ryazG x alA AADA3 6247 cc~cuuu U MUM=j 1708 5826 AAGU3 CMnAMflr X CMA AAC.P 6248 CGrU= U CttCLAC 1709 5827 AAAAXL..G Ct7XALA X CA AAAC-A 6249 ctuuw c cCt=J 1712 5828 A.A CUGAMNAG X 03A .ALCAAA 6250 CUUXttC A aiUUxttu 1715 5829 GCAAGGMA CIXPUGLG X CA AGPAWA 6251 UEMttML U UtItCurxC 1716 5830 MMMA CLGUA X 03A AALL 6252 tLtCCUA U trCUtrctC 1717 5831 AGGU CtLUALMG X 0A AAAGIAM 6253 cam= u caxt)U 1718 5832 CPOGA CM.UGix X CMA AAAGIA 6254 CEMCUX c CULC 1722. 5833 tUtAG CUGAUiA X CS A AGGAAAG 6255 CUtUrU= U CttUCAA 1722 5834 aLXrmn= CMfAK.AK X CA AAGGAAAA 6256 tUtJIucut C CtCrAA 1726 5835 GAA~aW CUM)GAG X CGA A0GA 6257 OC~tt-u C AAAGrx 1733 5836 LWOAMfl3 CtIGAIGA X CM AOUUtmA 6258 tCAAGJ U CCAU=r 1734 5837 GcXnAAin CtLLIA X 03A AAGCUUL 6259 CAD J C CAUUtCX 1738 5838 03Atn= CUALIGAG X 0A AL1GAAG 6260 OtJEULX) U QCAT= 1739 5839 COinn CUGAUGA X CGA AAIL3A 6261 aCrUuU C CAAU0 1745 5840 CL~a CUGAL112 X C3AA AUGMA 6262 UtXXM= C C3AGA 1769 5841 UGP7kCL13UGA X 0CAA AUUXAIJ 6263 AAIfAMAW U UtJCUtWA 1770 5842 CEMM CMA~iW3 X CMA AALTJW 6264 AAMLiU U CU!ICA 1771 5843 UtrtniA CLM X CMA AAAUMAUI 6265 AIOXJUE C tflCAG 1773 5844 CAMO CtX;UM X 03AA AUM= 6266 G~AME= C LMCAGAU 1775 5845 A = CMAUMG X C:A AGAAAAU 6267 AUUU= A CAtflr 1783 5846 GAAA0 CUGtflG X 0CAA ACAI=t~ 6268 AAIG J C CCI3UUtX 1788 5847 AGE)lXMA CUGLIMG X CMA ALIm.GXA 6269 IGLtLAU U tU~LAU 1789 5848 CAGIwU CLG Kg X A AA1 6270 GUC U UCGL 1790 5849 GCG CLIMxG X MA AAALI= 6271 MOM= u cw-4c=J 1791 5850 AGCP= LIPIA X CA AAAAI= 6272 COnUwrJ C AGCLr 1800 5851 uutXurnM CUMIGA X MAA AGC2J 6273 NAOflU U .AAAAAA 1801 5852 UrUUULutEw CLGUA X 03AAGGC 6274 GNMWUr U AAAAA 1802 5853 AM=~uju CUMOGA X OMA AG 6275 AMUMU A AAAAAAWI 1811 5854 AMMA CU3U)2; X CA AUEXXfXI 6276 AAAAAAAU C C L T. IAM 1814 5855 CAVJA CIGAGA K COA Aiw..u 6277 AAAAIXX U CUM=~f 1815 5856 G=BiM, aLX;UyG X MA MG =6278 AAACCUJ C UALXMC 1817 5857 tAGkM =Anii X COAAkGU 6279 1 AM=t A AMfLMP 1820 5858 GMD CttwxUGA X 03A APN 6280 CLUXf.AM C W3IA=f 1825 5859 LTCAMCMJA x aA GAW 6281 AAtfl= A UCLXP;A 1830 5860 U033= CUMMAG X OA AGCUM 628______UGAU 1845 5861 UtXX=~ CUGAU= K aA AC0fl 628_____A__AANA 1859 5862 utJ~Im aiumG~ x o:A Actxx= 6284__ _________A_______ 1861 5863 AUIa=t~f cIx~qxmG K a2A AMLUJU 625_______C L1CA 1870 5864 LXXMLIAA CLGUA X OMA AULJX=I 626____AAUA__AIO 1872 -F 5865 ALXIj= CTJGAUGA X CCA AXXI 628_______UALM 1873 5866 AALXX=I CLX~K X IIA AA =~n 628________L3CAA 1881 5867 AAitLMM CLGL7; X OA ALXXI= 6289 AL130AA U COCAGA 1882 5868 AU CUGAUGA X CGAALX 6290 LIOAMD C CCAAUJuJ 1889 5869 tn'Xjryt. CUMUGA X CGA AfLXL0 6291 UCCCAG U UGAGAC 1890 5870 CtmnUxA X~t K A AAULC= 6292 OCCAGA U GU.AA 1903 57 AXMM aXllXW. X OA AixM= 6293 ACAAAU A CfLIMJ WO 00/61729 PCT/USOO/09721 Table VI. Hammerhe. ibozymes to IRF-2 _______ _1 27 1906T 58-72 tUhAAAL11 CUflAIXG X 0AA AGLMXMt 6-i294 AX=fl~ C It 1908 5873 axwtAn ctuzmnAc x amA Pr~amJ 62-95 AActUA A MXWtr 1911 5874 CLXXUM CUC493LPG X CIMA ALXMtAG 6296 ACE)2IA U C~kAC 1912 5875 UfLtjGjrjA LIGUSIA X CErAA AAUAGG 62-E97 a.Mp.Uu C ucu. 1914 5876 atrtC j CtrPinG X OA AGAUG 6298 CUL.AL=~ A ACAA 1928 5877 AAAUAA~ CUMLIGA x aAA AOCUtI 6299 AGAAOU U ULIxxDn 1929 5878 -AAAAIAAA CtLGGAcJA X CGA AAGLX73JI 6300 GCAAPDrU U UEJXIJTJE 1930 5879 AAAAA1U.A CIAUMG X CMA AAAG= 6301 CAwM U ULMnuuW 1931 5880 AAAAAALTA CUMMAG X OMA AAA=J 6302 AAGtUUUj U UA.UUUEILJ 1932 5881 tU.AAAAAU CAUGAG X OMA AAAAWU 6303 AGCUUW U AUXXXMtX 1933 5882 ALMAAAAM CLXMIC X CIA AAAAAG 6304 GUCLXJ A LXXI~TLXU 1935 5883 GMAiz.AAA~ cIUMAG X CMA ALVAAAAA 63059 UULXUW~ U UUUEXUAC 1936 5884 tUA C UOGA X COA AALAAAA 6306 UUUEUAMX U ULXXMIkCA 1937 5885 CflMflA CMfALUM X C3A AAAIUAAA 6307 ULXXJU U UtLD:A 1938 5886 CCSnM CUMI1A X COA AAAA 6308 UUUtUtLrJx U UAAA 1939 5887 OCCLIOUAU CLIMLa X 0:21A AAAAAMPA 6309 WaXAMi U ALL~i 1940 5888 CCCCUGM CMALIM X 03A AAAAAAIM 6310 tULXJUU A UAAO 1942 5889 utLttctn caKux; x aA A1IAAAA 6311 UUUXt A CAO3A 1952 5890 CAAAA CUADM X 0:2A AXXT 6312 ~ A3AU A UUUrAUE~Jr 1954 5891 UU2ALPA CUMDUG X aA ALMUIX= 6313 G33AAUAU U UMMXA 1955 5892 CUAxIA CLXPIG X CSA AAIUJtXr 6314 AAM~J U UALXXAAG 1956 5893 CtUflAAfl CtLIGAMA X CaA AAAIUfl 6315 CGAIUU U AXIZV 1957 5894 ACUUA cuGALIGp X C3A AAAAUADU 6316 AAUM=XX A UMMOM~ 1959 5895 UMCUM CMAUMc x a3A AIAAA 6317 tPIMXXXWf U CAGLA 1960 5896 LXtXIA J CL7UG1x X CKA AAPAAAAU 6318 AuUrXTIM C AA03LAA 1966 5897 UtGAA= CUM X CMA AU 6319 UUEXGCJ A AAAU=L 1971 5898 urPUrXIA LIXPLG X CMA ALXU 6320 GGLAAA4J U CLAAUAA 1972 5899 tttUM ULA CIAUNG X OA AAULXk 6321 GMAAAJ C LUIAAPAA 1974 5900 ALtTwUi aXIGAIA X COA AkXMX 6322 AAAAUUCU A AZAAWAI 1978 5901 utLX.UV CAUxGsG X 03A ALTfPZ~k 6323 ULIXUAA A AAAELMM 1983 5902 AAtJAU CULIALA x aA ALXXWL634ULMA UAX 1985 5903 AAAAOlCAU LGA x a:A ALMWUXA 35UHAI AXG 1988 5904 tkAAA) CLIMU X CMA AIXP= 36 AUALUUGLXXI 1991 5905 AGAMA_ CUkUAG X CAA AkW_637 AUAAU___ U _X___ 1992 5906 AAGAMAA CLIGL7M X CAPA ALAXUk 38 LAMMU U 1993 5907 AA~jA animLr. x EiAAP~LXJ 6329________UUMI _ 1994 5908 AAAIpA. CIAx IMG X CM AAAACAtJ 633_______UU A~J 1995 5909 CGAAG CU3X2 X CA AAAAA 63 X3XX UU 1996 5910 AGAA aLINuM X OGA AAAAAMA~ 6332 tfLXXXWX A UCriU= 1998 5911 aLOLA CLxML7GA X OA AAAAAAA 6333 ULur1JrIu C Uurxlaw 2000 5912 CLILAACLGAM X COA AGAUAA ~ 6334 tUUtttJ U UULACAG 2001 5913 GaKXIx~ xLPOA X M AGU 6335 ULtPAnX U LIPU 2002 5914 UCIMGCVGArM x aA AGM 6336 ULM=XI U CLCG 2003 5915 UMMMA xLGAM X G AAAAGAM 6337 UAX!(II C =MG=A 2005 5916 AULXI= CUPMA x a2 GAL 6338 Uat~XU A ~AOAM 2014 5917 AALII xM0M X 3A U 6339 CACAA U AIXJ 2015 5918 AAAAI.tw aCLIMLI X 03A AAXJ 6340 AIfU Tj AUU WO 00/61729 PCT/USOO/09721 Table VI. Hammerhc -abozymes to IRF-2 _______1 28 2016 5919 tU.AAAuUt, C tmum x cA AA~uuuoc 6341 GAAAIUU A U~AIUUUA 2018 5920 CULPAAAU CaxALXx~ X ZA AUAAIU 6342 AAAIJEJEAf A AUUXXtzr, 2021 5921 AAMJUAA CtflALMiA x aMA AUMLAA 6343 UutMiLU U txULCAU 2022 5922 GAAIflTM CflAMA X CGA AALXMIMJA 6344 tUUAXJ U UAGULI 2023 5923 tWAZMM~t CEXWflGS X E A AAAIMtA 6345 tUtAAUU U AAAUUC 2024 5924 AGGALICU CUXP,[7AG X CSA AAAAUIAU 6346 AUAIUUU A AGIAttV 2029 5925 ACAAAGO CMXAUGAG X C:A AtLUMMA 6347 UUUAAGAn U CCuuutru 2030 5926 AAGAAAG CMIA X CM AAUCUOAiA 6348 ULMPAAM C CUUUtU 2033 5927 AAAAGA CUUA X CaA AP 6349 AGA~UL U UrrtmxLIJ 2034 5928 AACAG CEXMflA X MA A~AAU 6350 GAUtL=~ U tUtUflJ 2035 5929 UAAAA CUMLfl X CMA AAAGQWI 6351 AIUX=W U CMUtxu 2036 5930 ALMAAAA CLGA X OZA AAAGGA 6352 ULXL=JU C UtXXLtXW 2038 5931 MfAU~AA C MI X 03A ACGAAA 6353 CCXX=~t U G~UtPIC 2041 5932 MCMrAM1 CU~in X OGA AAGAA 6354 UtUtCUG U t~rAtaX 2042 5933 CLIOC= CMALM X COA AACAAGAA 6355 UCYJ.XMJ U AUOI 2043 5934 ACtfl= CLUALGA X CGA AACAG 6356 LtUX=l A LIACAX 2045 5935 CALX= CMUGA X OGA ALUAA 6357 tUtUI C AGAU 2052 5936 GAAflAAC CMLI X CCA ALIf~XXX 6358 tLr-GCG U GUMtPUAC 2055 5937 (AIflPn CUUJA X OMA 0fl~ 6359 GCAGxnJ U ALM=I 2056 5938 GGAULIAA CrALICP X OMA AAA!fl 6360 CAXlJU A UUACA= 2058 5939 AIflJ CLIGtMDG X CGA AtLACC 6361 GLJtFXW U ACLK=J 2059 5940 C~A= CUGAD; x aA AEACA 6362 tULXPLJAU A CAUCtLJG 2063 5941 GCACA CELIGAGA X CA AZLMAUA 6363 tWAtXMn C CUM 2066 5942 UGUO=~ CLIMPG X COA AGWH! 6364 UACA= U GLOCC 2076 5943 UPAAAAAA CIAxwxAG X OA AOU= 6365 U33MCA U ULtJUXtXt 2077 5944 UEMAAAAA CtJADXPL X 03A AAfLh33 6366 G3CJU U tUUUEX]A 2078 5945 ALtPMAAAA CUIGAML X CMA AAALU= 6367 GCAJUU U UUMUUEPAM 2079 5946 AAMrMAAA CUMUSA X CIA AAA=lJ 6368 CIAtAtMt U ttUtWXMAMX 2080 5947 AAAUTPAA CLIMUMG X 03A AAAAAIfl3 6369 AtXAtXXJ U U tJEPA = 2081 5948 AAAAUEPA CUMVLxAG X OMA AAAAAAMf 6370 CAIXXXW U UttLPJU J 2082 5949 CAAAUIX CUGX3AG X 03A AAAAAAAU 6371 PILJXIX~tXU U UAAULtfl 2083 5950 ACAAUU CLGLIA X CGA AAAAAAAA 6372 tXXtXXJJ U AAUXXEflJ 2084 5951 UWAuna amuoAG K CM AAAAAAA 6373 tXfXXJ A ALIXMf 2087 5952 CLUPO KLGUA X CA AUMPAAAA 6374 LXJLUTAJ U UUMAWL 2088 5953 aCLUXVM. CL0AIG X CMA AALPIAAA 6375 tJUtXPAW U UGIMAAM 2089 5954 ACiXM CUMX MX~ CNA AAWPXAA 6376 tIXWAIXX U GLAAPWJ 2092 5955 UUCAtu CLGD; K CMA ACAAUU 6377 AAUJXImJ A AAG3UGA 2108 5956 GCCA CLIGAL X OGAPO 6378 AAAAWJ U UXWGAO 2109 5957 AG32xxw. CUAEM X COA AAGCXJ 6379 AAAJU U tUMJ 2110 5958 CUMLIGA X CCA AAGfLJ 6380 AAUtG t U AUGAn 2111 5959 U = C1AUGAG X CMA AAA~iXU 6381 AAGUmT A W. 2118 5960 tUGCLMG CLZIXL X 03AACX 6382 MU = C AULG 2121 5961 GAMOM xUAUA X A AUXP= 6383 GACUA C tUAA 2123 5962 CtUnt= CLXI A K CA AGNX2W 6384 GC~IflI A GCAAUXAG 2129 5963 GAAAx= KUAUA X A AL]aM 6385 aLPLOW C AUX1M 2134 5964 CAG AA r KUUA X OA AMrGA 6386 AAXA= U U M~ff 2135 5965 CCOM a KUM X CA AMflMD 6387 AUCAMWt U nua= WO 00/61729 PCT/USOO/09721 Table VI. Hammer. .kbozymes to IRF-2 129 2136 5966 _| LAM COGUG X CGPA AAUCI A 6388 UCPG2uu U C Where "X" represents stem II region of a HH ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20: 3252). The length of stem II may be > 2 base-pairs.

WO 00/61729 PCT/USOO/09721 Table VI. Hammerh libozymes to CDP 130 Ps Seq. Rz seq. I.D. subtrate I.D. N. NO, 33 6389 A4XCA C..LDGAG X CM. AGeCu 6929 Cor3cT C 'OCCAMr 48 6390 GLMCC CGPDAmG X CGA AcIC 6930 GIrEtr T GIX03C 55 6391 -GXt CUAmG X CMA AaCAA 6931 nuGIGMur A 03aM 69 6392 CLCaCmr CLAUGCG X CGPA AICU 6932 AGE r T GWA 82 6393 GUTCA3 CEGmuG X CGPA AWx=f 6933 AGMACT C GPCAC 100 6394 tUTCPA CIMGAGG X OPA ACrn 6934 GCA-Cr A TI MA 102 6395 = CEG X PA AL=A 6935 AM T oGMCC 132 6396 OaXCG CUGADGAG X COAA AC A 6936 G C CAG 145 6397 UMUM G X %A A== 6937_ AAGOrT T ATOCA 146 6398 ax aX),4 X CCA AAOCJ 6938 AG03= A TCAAA 148 6399 a==U CUGAMA X CGAA AUAG 6939 C C GMCAGAG 165 6400 umrUtG CDtATA X CGAA Aarm 6940 C0333WG T CAGA 166 6401 Uxiun auxw x eA AAC00CG 6941 Cr_ _rr C AAGAGPAA 179 6402 ACnC C X CGA AGxtU 6942 AGAACACr C CAGA 188 6403 amCA CAGG X CA A A== 6943 CGP=AT TGCOmCMG 189 6404 GCUmG CUamiG X CGA AADCCUJ 6944 ACUGpaT T GmCPkA 202 6405 AGm auGAG X CGPA AC=GCU 6945 AAGC _ _ A _ u_u__r 221 6406 uxiGA CU X eA xamACIxi 6946 7GMAAr T TCCPnA 222 6407 aCDCm CiAUmG X CiPA AAn=CUC 6947 GAGArr T CCApACG 223 6408 tUa=nx CGauurG X C:PA AAMCUU 6948 AWrrr C CoAAGA 235 6409 AGLCADC C XAmG X CA AImIC 6949 GAGAT T GPASIr 248 6410 GC XjUU caxDGAG X CpA 24I l 6950 CAM r A AAACADC 275 6411 ADUtGA CUMVrG X CGPA AGC XOU 6951 AAGCAGr T 7crIGP 276 6412 CXXAMmG aAUMG X CGPA AAWIIHJ 6952 iAGCA'r T CrIGAG 277 6413 AAuxA CamumG X 3PA AAAmr 6953 Grrr C TIMA=~ 279 6414 AGACAIX CLAmeG X CGA AGMAGU 6954 AG'rrCT T GAA7IC 286 6415 CCUUAU CIGALIG X CGPA ACADDA 6955 TIGAaGT C TA G 288 6416 ADCmUD QIMUG X 0eA AGCA 6956 GAA'ITr A CAAMGT 297 6417 CMXAAt CUamAUG X CGPA AIfLXXE 6957 CAAMGAT T GATGP 301 6418 COMC caIMMG X CGPA AUMAU 6958 AGATIGAT T GACGr 307 6419 GALUG Cow=G x CGPA AAoZAu 6959 ATIGA= C C~Odo 314 6420 UMUMa CUaONLG X GPA AIDI.A 6960 MOCAGAT C 'CamC 319 6421 AApm CiaxMpUG X CGA ACGINE 6961 GA7II A MDrrr 326 6422 Ga Cwm DiG X CGpA AGflIL 6962 TACro T 0pAMi= 327 6423 C~aGAI= CaIMUG X CPA APG:.J 6963 A rr T GPWa 332 6424 aGHIG CiatmG x CaPA AulAAG 6964 CIrITr C sImCLA 334 6425 tIDI= CXamXGX X eA AGAUCPCA 6965 TI1 r C onCAGr 346 6426 LIGl aIugG X CGA A00X= 6966 CPGCr C CA=MA 352 6427 u~m= aumam x CaA AxGI G 6967 C3r C AGrA 374 6428 tflCXXA amnG X CPA AuII= 6968 GCACT A TIGMAC 376 6429 txrnu aumG x CoA ADa 6969 CAC T GAAA 397 6430 GUOtIU canUGw X CGA Aajrjf 6970 CAGAACr T AGGGAMC 398 6431 AGCuT aIGr X CPA AAjXU 6971 AGAMLrr A G32ACT 407 6432 XvEDCA C7amG X CPA AaXI= 6972 0GAAC C T3AAGAA 417 6433 Xm 30 CamPU G X CPA iXm= 6973 GMGAAT A CmMG WO 00/61729 PCTIUSOO/09721 Table VII. HarnmerhL... -- &ibozymes to CDP 131 429 6434 CJt7Qm caxw- x a Aux~!J 6974 CAM T tAI 430 6435 ALUECAG CtUA X CXPA AAIXJ1J 6975 A A'rT GCIGA~r 46 6436 AAMXMUt CV,-jL--A X OMA AMXtX 6 7CtA4AA C AMA=r 454 6437 tJUJtX= CUAUGA X CMA ACtCU!J 6977 CAAM= T ACAOP 455 6438 tUt.t= CLUGG X CtMA AACMJ 6978 AAA A CGAAA 460 6439 AGJC= CUPOGA X COA AMMA 6979 GInAGA A AAG 469 6440 tttUUtl CtWMLG X OMA AGOG= 6980 AACI' T AA~ACAM 470 6441 tjtinnjt CMUL X OA AAL32O[ 6981 AAGC=~ A AAAGA 481 6442 tULMtUt CGAUMG X MA AUX-ttfl 6982 GAGAAAT C CGGAM 489 6443 tLfLUUtM MU~a X 0 aA AUUCU03G 6983 CA A 'GIMA 523 6444 UCfAOCE CUMUG X CMA AL13GUE 6984 GAACA A GCITI 527 6445 CUrUCA CtLI2 X CGA A~M 6985 C~T~ C T7G;GW 529 6446 UrttxtUr CUGiMA X CGI AGAM 6986 AAIT T GAVV 546 6447 CAUrUMO CL13ALXMG X CAA A)LXXIh 6987 ACM~ T ACAGAAM 547 6448 MAW=xn COAxUix X CGA A~AJOUM 6988 CAMi' A CziLAATGA 558 6449 UL7tr7)= ctxU33kG X 03AA AUCxt 6989 GA7K9 T TMAA 559 6450 UUUtmn CLIMLM X CrPA ANGXXU 6990 AAGCrr T GCAGAAA 597 6451 AGO03U CUGAIW X CGA ACAUa; 6991 AAG= C CACN 606 6452 OCACUU CtIOMMG X A MGM 6992 CAr7 c AA~I= 629 6453 CXACU CtLIMG X O:A A13CL10G 6993 CIk= A POMUGI 634 6454 2Arrtn CLIGAU:G X Cr;A ACJtW= 6994 CAV T CAA 635 6455 tUAflJ CUCIPL X CMA AACCULW 6995 AVrr C AGG 643 6456 GnCUS cUGAUGA X CGAAG 6996- CAA A CAA 665 6457 UtnrU= CUWGAG X CMA GXXJEX 6997 ~AAAAACr C GACM 675 6458 GaXAAUn CIAxUzG X CA AMG 6998 AACMIAT T P=T5 676 6459 AGGlAA CIAtXPG X CGA AAI~flfl 6999 ACGA~ A TrIG=r 678 6460 UOG= c~~xN x aA AUALXLU 7000 A T T TLrI= 679 6461 ULXA= CLX!V1M X OA AAEUAA1X 7001 GAM=T T G@CIGA 696 6462 CaXXM GM X OMA AXXL 7002 AAA A CGI; 710 6463 aiUUtCA CUAUGAG~ X CGA ALUXlX 7003 AAGAAA~Cr A M=AW~ 730 6464 AUrAU CUALIM X CGAA AM=flf 7004 GMA T GmAAA 739 6465 U009=n CL13UM X COAA AM~U= 7005 GA~a C AMa1 751 6466 GCCX=x C~kxMG X CGA AGG J 7006 ACM T GAP= 782 6467 cann CiGAVM X CA AGO=5 7007 AM=1~ C AGGA 801 6468 GXUJI CUOUDM X CP A=lX= 7008 G~GC T AA33 802 6469 tLX= aXPLWG X C3AA AA:; 7009 GP A AGMA 814 6470 amm axxGcx am ~A 2fxx 7010 GAADAG= C I= 816 6471 umom axmizw x am A~pa= 70.1 AM C AT3= 8M 6472 GAUU33 CUAJ; K CA A[XMOC 7012 GCC C G3CA 827 6473 GAGSG CUAxUx X CM 1LX 7013 033::; C AMC=~ 831 6474 GCrr3M CUPOGA X OA NXL 7014 CACr C 071CCA 835 6475 an amr mG K cci a 701.5 ~CAiT C CAC 846 6476 cxwnn anWC;; X OA A= 7016 GZIGr C ACGa 853 6477 OCxCUtn CUAIGW X 03A AnM= 7017 CAAGT C CAAX 883 6478 A=xtr CUAL~X~j X CGAL1 7018 C A OI A 900 6479 aparm cumrc K c3A Aa 7019 GACOM C CAM 9U7 6480 TX;A=LX am~xn x ccA xmxm 7020 ==~ A GW WO 00/61729 PCTIUSOO/09721 Table VII. Hammerf,.6Xbozymes to CDP' 132 913- 6481 G(CAACM CMUvi2; x crAzwrT- 7021- 7AArT G 918 6482 U03==~ Ctuu=G x am ?AUALT 7022 rMrTG03M 940 6483 AGXTXLI2 CtrAuj X 03AA AUmrCO 70-23 C3GTC AAr 97 648 aa pM3ajiG X 03A AGLrlX 7024 AGArCA3O7 982 6485 aXMaMG XOAAXM 705 GAG C Xi= 1_0_01 6486 M=CU GX M UL 72T 103-5~ 64 GLU .CXO, x CMA Kintnru 70-28 _AOAA C TCC~ 1057649 AG JGU U CLML1AG OM AGU U3Cj 7 31 G AAACr C AAACAAL 1123__ 649 GALCtA xWM X A A~aXJEG 7034 CIA= T CIG)%ic 1124 _6495 GmaxJEA cuum x aiA AAL13UUCA 7035 - rrAA C TGAG 1131__ mm ax~uGj X CMA AUXMk 70_36 wITGAAr C CA0G~ 1140__ 649 AMxIGM xGU X M CK 7037 CATGr T rTGO= _41_6i98 GCxx anqjM X~ AALC=m 7038 -AOM=r T GZC 1149____ -cc=r Cuanmr x ccA ALU7A 7039 TocAI c 03GM 117 E-- rzr a=UWi X OM CGA 7040 GOr T GZGG~ 1215 _6501 ACMAX CuA~iC2 X C~A AG3( Tz 7041. c C70A~ 1224 _6502_ CMXX)fl= LMUGAG X OMA ALMflM 7042 GCrG= c CMGAA 1246 _6503 Ci3:2L ctiGA7r-A X aA AUCO 7043- cTGC= C 7MAM 128 ________ cUaX aimtiG x ~a 2 5 wo= T7044 -G.wr c CACxa 1269__ 6505n~ UCCIGXU xLUM X M ~M 7045 GA03 C AGMNG 1304 6506 _ 33 axwjm X CA ACLUJt 7046 . cimAwr c 00 1317 6507 CCA CuA~iGAG X C3A AU33 7047 CMA C Mu=~ 1319 6508- CDOOM, CUMUG X COA XWJ 7048 MX;=T TGCO3C 1320 6509 _GCC0Ic cumWiM X 0:A AAGIJ 7049 GOGAr T 000 1334 6510 CULGA CUALA X CA A03 7050 ctW C lcIW 1337 651 aMMIM aMU X CA AGAG 7051 CC== T arrG 1338 6512 MC~Xr a~xu x c:;A A~A=f = 7052 COIt T C G 1340 6513 GaDMIA a)jyjGr X COAA XpGM 7053 CIC1wr C AGrU= 1344 6514 t CUMUMO X CMA ACM 7054 TIwiCAr T COO. 1370 6515 pA~uur aivzm X COAAaX 7055 AGM T 0AML'r 1371 6516 tPOrI,= axx x a;A AAO= 7056 GCAG C CACMh 137-6 65-17 _Amm ajmmxmG X OA AUtXG 7057 LMUCAM A Cnk 1379 6518 tfLPD= axwUGA X 0A GP 7058 CAMVr A AMM 1385 6519 Mxn Mmuwja x a3A Aou 7059 CMA=~ A CAACA 1395 6520 axJM axwuG x amAx 7060 ~ACA T CI;C 1396 6521 GWflA ciGxAG X CA Aa3= 7061 CACIT= C 'ICAC 1398 6522 ca x~i= xLU)A X A AGC 7062 CCrAtr C ACAO 1410 6E523 ==L=ajr aUMXM X 03A ACOO 7063 AG333 T AAIMAG 1411. 652 4 tru1GAj anUXW X O:AACC 7064 G0333 A AGOA 1415 6525 -AAJGjJ CUU X 0AAUAC 7065 '-Gr~kr C AMP=T 1422 6526 AGIGA CLUU]MG X OM CLX 7066 TCAGCr T '~ 1423 6527 Maz x aj=)MG X AA n 7067 aPVL;L T I;IC WO 00/61729 PCTIUSOO/09721 Table VII. Hammerh, C~bozymes to CDP' 133 1424 6528 rJACfLM CUG~uGA3 x aPA AAG=U 7068 AErIT T WAG=I 1425 6529 AMI~arl CtJGALAG X CGA AAAA0JC 7069 AGCrrr T mou 1426 6530 GEI L Jarmi X CXA -AAAA~ 7070 GACrrrrr C AGt 1431 6531 CCA03C-nAU COfAG X CMA ?AMA 7071 TrrAr C AITWIC= 1434 6532 UtXC~CEX m xM X G ALA= 7072 CAGi= C CMIOA 1453 6533 GCCA03M CGAUCA X 03A AG3CXt3 7073 CCA r A CCCC= 1463 6534 UtCULIAG COUA X CMA MON 7074 CCCr T CnCAG 1464 6535 UUtMU CMtriA X OMA AACAG 7075 CtII C ITACGA 1466 6536 UUUEtL= CUCALEO X 03AA AGAC 7076 ITI'ItT A C~AAAAA 1476 6537 UUGLU CUUAG X CCA AILXttt 7077 AGAAd' T 'GCAM 1477 6538 UULG= CUGAMA X 03A AAIUtt= 70*78 GAAAATI T G~CAA 1483 6539 ~AGAAG CUALA X OZA PGXAAA 7079 rriGCrC A AACI=I 1488 6540 GGGAG CU20Mfl X CGAA AGLUMM 7080 ACnACr C wrr=i 1490 6541 CUMAGI CLIUA X CGA PWX 7081 TAA=c C rTICC 1492 6542 C3MI3G CUAUG; x a!A ALGflAX 7082 AACI=I' T CI=B 1493 6543 OCt~axm CUA~UG X CMA AAGGAJ 7083 AMC=tr C TCA 1495 6544 trxrmx Mo-ALU X CGAA AGAL~ 7084 TCM=w C CAO3 1507 6545 CAMX70 CMxwG X E5A 2X ; 7085 C30 r A MGM=I 1515 6546 AGUALAG CLIGLIM X CM AC.UIX 7086 AA'IG= C CrIwC= 1518 6547 tnGGUA CUAIG; X OMA ?LX3A= 7087 GCAiw T C==t~ 1519 6548 UtMG CLIMLIG X MA AAGGAC 7088 CAGITrr C TACXA 1521 6549 CCLItX CUAnMuiG X CGA AGAM 7089 GlTCrlt A CCtAJ 1524 6550 UAGOn CUL1XPMG X CIA AGAGA 7090 LcrlCT= C CAGZ 1532 6551 ULM=t CUGAIGA X OGAPO 7091 CON A 'IGCAA 1561 6552 GUXXA C1LXAU X MA AUCA=l 7092 AGA T TrIIPC 1562 6553 tLGt~im cumI3= X aA .AAXLT3I 7093 G3X= T TIAC 1563 6554 CUGUUGA CaX20= X C[A AAAI3fLr 7094 CARP= T TICAAPA 1564 6555 CtUGMGA CUGAUMG X 03A AAAAICAJ 7095 ATIT= T 'ICAC(3 1565 6556 ALttmn CLUGAGP X CMA AAAAj 7096 IT'ITIT T CACAr. 1566 6557 GACULJU CLGUGAG X OA AAAAAAUfl 7097 GTTI C AAAG 1574 6558 GLUMM CUAUIxA x a 1A AflJGUM 7098 CAACAGr C CAM 1578 6559 UEXX= CUALzr X OM U3 7099 AICW . A CACAA 1590 6560 AGAUA CLIMXMG X OGA ACXUMn 7100 @CA rC C CAV 1594 6561 U0MG CUMOGA X OMA AtLUMO 7101 AACItCAT A WIOIA 1596 6562 tJXIMMA CLIMB X 03AAM3 7102 MCC= C TIcomm 1598 6563 .ACrnTX crxwr= x aPA AGAUAUG 7103 CU.~trT T COOULr 1599 6564 GACUUrM CUGAUGA x a2A AG 7104 CAU C CCAA~GI 1607 6565 UUGLAif CUGAU= X 03A ALUJr=t 7105 CCAAAr C CAM 1611 6566 Urxnmi CLXIUM X OMA ALUM=X 7106 AGICCA T ALC~AAC 1612 6567 CUUmJW CUAxUtx X OGA AAA~LU 7107. AIU= A CACAA 1630 6568 A1XXZ2= CLIGJLI X MA ACu 7108 COGA C AMU=i 1647 6569 GaCUtm3 cuAuj x aA AtI33 7109 G30= COOC 1659 6570 ~CAuLtn CUALA x a !A AC3 7110 CA~G C A~kb 1678 6571 CM(M~ CUGA= X 0A A0C 7111 G02 C TCM 1680 6572 CUCC= CuLIMI X OMA AGO 711 IAGO ' C MUA 171.1 6573 tflO= CMfAUGG X 03A IXIXIfl 711 GCNAAT C . 1738 6574 UnUGU= =U = X OMA I1 7114 CAO=T T AA1CM WO 00/61729 PCTIUSOO/09721 Table VII. Hainmerh Cibozymes to CDP 134 1739 6575 AD~LXUU CLAx~in X 03A AXIflCu 7115 .DAr A PO)MA 1748 6576 UUM003A L CMAGX aA 'IAtXU 7116 AGCCAAT A TCISA 1750 6577 CGtUGxItC CMAUGA X 03A AUAU0ff 7117 CAAT C GGAPAA 1760 6578 UC0AAAA cAmAGn x a:;A xAtnr 7118 CAA= A rrriOnA 1762 6579 ttIOAA CUrAIJJG X CGAA AiLLtfl 7119 CAI= T TIC3A 1763 6580 -LtML'CX CUnIJG X ~AMAMCMU 7120 AMU=~T T ITCOAA 1764 6581 AAflGt CtmAt1A x mm MAt 7121 AG'rr T COSACAr 1765 6582 MU =~fl CUmm.A x ccA AAAAIcG 7122 -02rrr C GCAATIA 1772 6583 aA~c~r- cfl~tfl x CA AUIOMCC7A 7123 TCGGC T ATGI=r 1773 6584 CCAACC CUIfAJJ X a:A AMU=t 7124 C3A=7J A wi7GTIM 1779 6585 ACAxcc CtMMM X CaA A~atr- 7125 ITATG T G3CIAT 1788 6586 AtCutn cuuGA xt~D mm ~Aa 7126 (G3Aci= c TcA 1790 6587 0LttUU cauisA x aA AaCN~ 7127 Gj C;zI:I: C AAGGG= 1797 6588 03Ctn~ CGUiM X OA ACUXA 7128 'ICAGO= C C~G7G 1810 6589 -C03 Ci~rW3 X COAA At~EXU 7129 ADGCT T CI30 181-1 6590 CG3= CtXMEJG X CGAA A4XU7 7130 CGAGATr C 'IOt= 1835 6591 AMX~U cuaur.A x aA Aummm.f 7131 CAT A AACGkZr 1846 6592 UUMClM CUGAtnAG X ( A ACG _7132 CiTci- T CgIGCA 1847 6593 CLWCt CLMUP X OGA AANG 7133 MrAC=~' C GIUO 1863 6594 UMUGL CXIMM X C:PA AU30= 7134 GSG T ~TCAG 1864 6595 AIX.UMfj CMV)Ctr X OMA AA17fl 7135 (GAC=T T CAAAA 1865 6596 Cau~inrj CLUMMAG X OCIA AAAUI= 7136 AG= Tr C A.AG 1881 6597 cnMAwn cutXAuGA x amA ~Aurn 7137 GAACAGr T CCTIC= 1882 6598 trtMG a)UM X 03A AaX3L=E 7138 AACGrr C CITCCO 1885 6599 tEA0 CE ;IG X 03A A=WMf 7139 AI CTOIGP 1887 6600 G2UCAUC CLUiX X CGA AGG 7140 r =CCATA3 1903 6601 A33CG CLUVIX;G X MIA AfLU= 7141 AACTCIuX 1912 6602 AUxnMM CiUnAuMc X COAGM 7142 MO=cG = 1916 6603 tUtXI= CUUir.A X 03A ACA 7143 CC=AGACA 1921 6604 acnX cEXWX= x a A mtmmm 7144 0E) AGM 1943 6605 CE33U CMMUG~ X CaA AJX 7145 GGGA A3 1966 6606 Lt 1M CLAUMG x aA AL 7146 ACG~ rCG 1968 6607 curxrm CLUX9i X 03 AUW,=U 7147 __________T________ 1969 6608 AM=xt CLV3A X CMA AALPLafl 7148 AA=TCGA~ 1970 6609 uw~a=~ CLXWX1 X O."A AAAN=~ 7149 GA =CGGG7 1978 6610 OMU CLUM x c.A Aam= 7150 CGA~ 2 1998 6611. t;CxV cmwmr. x cA AaXXJ 7151 ________C_______ 2006 6612 00utn CLUUIXM X 03A ACWXMG 7152 tA=ACTAC 20U1 6613 am33uw aUGAUG X CGA LY 7153 G2lA.T C AON 2023 6614 ckGO= CLAKA X OMA AOCO 7154 AC03A C CGA3 2031 6615 ala CLUU)CM X 0A AGa= 7155 CCGA C GAGC 2043 6616 C axwUXM xUIA X CA AGCML= 7156 GI=C TGTGA 2056 6617 At~UGM CLAM X CA ALXWJX 7157 CP.AGT C AIC= 2061 6618 am~mm CUUA X OA ACLURM 7158 CATCAA' C CACCTA 2065 6619 tntnM CLUU.2G X OA AU..C 7159 AAIT=L C CIMWA 2068 6620 GCUJO=~ aXUM X CCAM 7160 'TCCA A GACA3 L2089 6621= CLIMLM X~~ C aA Atau 7161 rG3G C CAGIM WO 00/61729 PCTUSOO/09721 Table VII. Hammerh, 6ibozymes to CDP 135 ____ 2123 6622 UGCGn CAxLixG X MAA PArxtxn3 7162 CI -- 2124 6623 ALKLM3IG CLxwM X CGA AA2J3 -71-63 xLD CCC= 2127 6624 C3A=f CttA~uA X CZA ALXAAC 7164 c =c cA 21'33 6625 ctoumzr c~Ax; iG x 03A ALCWA 7165 CC3~) 2148 6626 GttCAtUCU x aN PGA=trJ 7166 C3ACTCGZkC 2161 6627 ~ALMG CU3AIr-,w X CGA Aimx3= 7167 AOATccm 2166 6628 GCAG CMUAG X 03AA AO3I 7168 CTCrCCM 2170 6629 t3MtnM CtxAixAj X 0 A AW 7169 COICA C CMAG 2215 6630 GCLAGJ aAXSc. X C~A AG30 7170 GC70=w c dc'c 2226 6631 Cactm aMAM-AG X CCAA AGrA 7171 CtC==z T AA~a 2227 6632 GCtLXUU anAtnG X OA AAG3A3r 7172 CCwitc A AACA 2244 6633 CAM=Xfl Cr-M)GA X 0:A A~GaJ 7173 AcLCIG C CCAG.iu 2257 6634 AGMMJj CUGA1UGAG X CS.A AM~U 7174 ~ AM4T C ACU=~ 2263 6635 G03LIAGc CmwmG x aA AummfAu 7175 ATA~CCAT C CICAC 2266 6636 titOM3nj CUarwrm x aAA IomuJ 7176 ACCA= C ACCC 2278 6637 aL3M CxuGVM X CaA Am~tn 7177 CtaAr T ciGMMC 2279 6638 GG33C CUGAUG X 03A AACXIUGG 7178 CCAAIT c TIGIC~CA 2283 6639 GCA~ ax)A X CMA AaVA 7179 Gz1ft=r C CAL 2289 6640 cr.AUn= CMUMAI X CMA AP~nC 7180 GrCCACr C GCC~AT 2307 6641 GgM axGwm x aA Ac~o= 7181 CACO c c~c 2313 6642 CGou= canriAM X CGA A~atfl;C 7182 GCAGiTr A CCA 2321 664.3 GKMO; CMU)L; X CCA AGZXX 7183 AMA= C 7IZC= 2323 6644 GAGA= CLIMDOAG X alA AGG 7184 CALVC C C~~CIC 2329 6645 uJGm cumuo x aA Aumom 7185 CIC3= C I GI 2331 6646 trrxrAM CMfAt X MA AGM 7186 -coc r c 07AC 2346 6647 @k~a= CUQMXMG X OGA AGMrjt 7187 GAG C C3 G 2354 6648 G=CAGr a)MtCfA X tAA AM=M 7188 -C3=f C CIAG 2370 6649 GMAG CUMUM X 03AGCP 7189 -033Ir C 70crciW 2375 6650 dXU033 CiwxMG X C3AGMM 7190 -CIC=~ C TGOA 2395 6651 ttvrrjur CLUXWG X CCA AG33C 7191 CC3Or C AAAAA~k 2447 6652 mtx1= aiGAU X 03ALM3 7192 CGCGT T GICA 2461 6653 t1JnX7G CXWJ=G X CMA AM=W 7193 CAAGO C CIGILAM 2553 6654 CCrOGA MMUGAG X COA M 7194 7GiO3 c CIOGA 2556 6655 aOtnu= CLIMUGA X CGAAMO 7195 C30Cr C 03AGGA 2633 6656 a3 auuxmG X Aa W 7196 GCCA C Mcm 2648 6657 MUM=n CUGVAX~ K A Aa]OU 7197 - AOO C AGIC 2653 6658 GMtMn CULIXW X OMA ~uAXL30 7198 AGICAr C CA03GA 2664 6659 cGAG~ cumr.~ x K m 7199 G33AC C G=U=~ 2667 6660 ACLUX2 CUMIxIM X CM a 7200 AMC= C GICAGAr 2670 6661 AGLMCUC CLIGxUM x-CA AOC 7201 uiui.r C AGAMV_ 2676 6662 ccura axcm X OM aX 7202 MGAOT~ A CT03AA 2703 6663 AGMIX= ar-VC; X OA AaP 7203 comxp c ctcc r 2709 6664 UaM:P ctMiU X E5A X 3C 7204 GCr=. A CICCX 2712 6665 AM=y aLIMUA X K AAU= 7205 ~ CLMT~ C CCAGA 2721 6666 tjmlr= aiUA X 03AA~X 7206 CZP0 C AGGr *2732 6667 CC33C aLIMUM X OA ACtU 7207 Aicwr c mI o= 271 6668 U0330A CLIUGI X K AMCA 7208 CG= c C..Li V a WO 00/61729 PCT/USOO/09721 Table VII. Hammerh.. .ibozymnes to CDP 136 2784 6669 OC=ItX CtiMLX,- X 03A AGMLrxIMC 7209 GC=CCCA 2791 6670 ALX1z aruMG~ X ~A ALI33a 7210 =CG = 2802 6671 E3DMJW mmuALG x crA AzLf33xz 7 222. GCcAr c CAAGOt* 2820 6672 CX LX CMflUGAG X CA AG33CUW 7212 -AG 2824 6673 AD333r CUEMGJ X c3NA AC3 7213 CCI3TCM = 2847 6674 ACACt~CEXPt XuD x A ACtflz! 7214 3G rAGiL= 2854 6675 UkOn.M CtMAX G X CMA A=U=iA 7215 mc m 2856 6676 i c CUX~L X C2AA AG~AM 7216 03IG= A CtATACC 2862 6677 ~C== cmXuLr3 x cA Aoxm 7217 CrMoj= A CCGM 2881 6678 GJGAG=X CGU)W- X CM.A AOfl 7218 c~m c~ CA C 2887 6679 tLUC03 CUG~uGA x aA A~~u 7219 AT~aQzr C ACtt33C 2899 6680 tUjU CflADCW X CIMA AM=tE 7220 C3CM T AAAAA 2900 6681 CtUM=t~ CafAL; X CMA AAC 7221 GGCP= A AGAA 2926 6682 ctrtOM CUPDGLG X CGA AMC=U 7222 AP3CT C TGCM 2938 6683 UCX~alA CUUA X CaA AILtXE=f 7223 CAAGA C ITM332 2940 6684 LUt = CLUU)MGL X CXMA Anrnr 7224 GAA= T MUM -2941 6685 UUTrt= CLUUXG X CMA AAM=~ 7225 n~AGA rr C G3f3A 2964 6686 tJOCt= CGAGA X CGA. aG 7226 G30C= C CAG3C 2977 6687 AUxGr= CMMA X 03A A3Cr 7227 GOA C AGCA 2991 6688 LXX CUGAUGA X CCAA ACAIf 7228 CAM C CCAX -3039 6689 UCC33A CtIMGA X OGAA AaXru 7229 AGAA ' T C703 3040 6690 ACOMl CtViJMG X 03AA0a 7230 GC=i C ATC03SA 3043 6691 tG(i7 CtKAIM X CrMA ALMAG 7231 Ctt'r=~ C L-GA 3055 6692 UXAG= CtMUGiG X 03A Man=~ 7232 AMGCAG C 7GOIGA -3073 6693 Cctt= CUAUGA X COA AGU 7233 G3r9 A GCCA 3085 6694 A03GA CUUM X CMA ALACC= 7234 -CM T Cnt;I' 3086 6695 G%3 a)GUMG X OIA AACAJ 7235 A033=~r C MkCO 3088 6696 tUcrn= CMUM X COA A~A1 7236 G3IGri A CC:= 3094 6697 LEW=t aCUM] X OMA AC3=5r 7237 cc= c CA O 31.18 6698 G aJxrG CU X~o x A Aa = 7238 G3G= C C7CtCAc 3121 6699 AiiMw= CLNIA X OMA AGCL 7239 CCAGr C ~CACTC 3126 6700 ALIMX=~ C1XWJG X CMA NAfLUC 7240 CICI= C WMCA 3135 6701 O=Mn~ a]L X EUA A fL= 7241. 02AA C CxCAM 3139 6702 cm3L= CGALzx;G X OA AC 7242 ~ACA r C CAa; 3171 6703 txmin= CUMUM X OA AGLN 7243 TIGIAG C GAAAGC. 3182 6704 G~xr= =AM X OA Aar,=t 7244 AAGC= C CAAO 3192 6705 A~aX= CLI.tq3= X C:A AGMICUrU 7245 AAAGAL'C C COCA 3219 6706 UaUi= CIAUw.G X OA ACX; 7246 CIBI C ccmm 3230 6707 CLu~tW CLUM X OA ALWXI 7247 03A7GAr T CCGTG 3231 6708 AcrA aiuo1AG x EUA AaL Xm 7248 GA7rr C CAGIKPr 3240 6709 UrrXX:P CUGAUGG X 03A ACLICAM 7249 CAGGAr C GGGAG 3265 6710 CUtflumumct x aA CA 7250 GAOiwr C CACG 3278 6711 GA333 CUMIGAG X OMA ACG0C 7251 AGO=I~ C C~CCC 3286 6712 CUX=r CU.-AM X COA AUM 7252 MOO C GA302 3336 6713 G3G.n axMUMG X COA AM=~t 7253 GCA C C3L 3342 6714 LU33CL CUXJVXGA X CGA AGO3 .7254 AI -cr CtMO~ L3365 6715 LratAG cUPIMG X CA AGCA 7255 C r c mmatm WO 00/61729 PCT/USOO/09721 Table VUI. Hammuerh, Ribozyrnes to CDP ______ _1 37 -- 367 6716 MUMMA~ CtGAXMr X CMA ANGC 7256 M~rrc GC 3369 6717 AL3Uflr CMALIGA X CMA ACiP 7257 GLIMCCSC~ 3378 6718 tMAG3CncuvcG xXi X IA ?LGflXX 7258 aAL-C '38 5 6719 tn3GAUGC CMAIGlG X CGA A033 7259 C =CAG = 3391 6720 AAIMMr CE.UIIG X CM ALXXCUJ1G 7260 CC=CCAA7 3399 6721 U33tCUT C Lt;iJM X C'GA AMMMU 7261 CAATTGM 3400 -6722 Mumpct cuaunm x a3AA AAImtaf -7262 ___________A______ 3403 6723 GAuIm cummpr x aCwA 7 2-63 CA~r A CCA=~ 3411 624 GoflX= c~AuGAG x cA AAU 7264 AMXwirG C CM3A 3429 6725 UwUrG C~AXJC2 X CMA AGOUC 7265 GaCA=t A CGCAA 3436 6726 CnajtUj CMAUMG X aA AIUGCOFM 7266 T~AC A ACCAGC 3475 6727 COMM=t CtGAtGA X 02AA AGGUUGLnU 7267 AATV TC GOCO= 3486 6728 Ot.Mj CMAM.N X 0:1 .AG'tfl 7268 CCG03r T ATIGI= 3487 6729 LttCAA CUGAUGA X OMA AAGO=f 7269 CAGO= A TIIG~ 3489 67 3-0 Ua=CrCtA CU~nxG X 0:A ALA= 7270 C3rrA T TG33GA 3490 6731 GCUtE CtxWGxG X COM AAUAAGO 7271 -CCZITr T G33AA 3502 6732 AotctIjA CM i X CGA ADM=xt 7272 GAACCA C T~ftG3r 3504 6733 MAO=~i CtGALM X CMA AGLX3 7273 C-=~ T A03 3505 6734 GUAODxx CUMUM X CA AALX=lI 7274 ACICT A G3I=C 3511 6735 CCUW333J CUGAUMG X C11A AGCTtA 7275 'In3O C ACAG 3522 6736 CGG~A CUAn uAx~ ccX AGU 7276 CCAG3r c G = 3526 6737 AGLOG CLCUGAGP X AA KAM 7277 GCxIti= C TCIOAr 3528 6738 GGG~- CtU.-LM X CGAAAAA 7278 CI=~' C TGACICC 3535 6739 cuwIVG x)UA X GA GAA 7279 WiCCIMc Irl 3538 6740 G3033 aUMMAG X CMA AGA3 7280 GACC=w T GCO 3560 6743. -AC,- CTIMP X COAA AMIXAM 7281 CtIGT A AGIr 3565 6742 MIAAM CIWOM X CGAALX 7282 CAA~ C AItICTA 3569 6743 tLtvUUUC C~-LI X OA ACU 7283 AOCICAir C VUUM 3588 6744 urcxim cu==G x cuAArG 7284 ACA= T 09CC3 3589 6745 A~C0M CLUUXi X 03AAG= 7285 GACIT C MCC= 3592 6746- U3) nir x E5~m~ 7286 OCrr= C C3A 3669 6747 GCLUCA CLIMUM X CAA AGCUXr 7287 G.AAG= A CAAG 3690 6748 a rzw x~wm X A AGCLU=f 7288 GCC~ C AGCG 3694 6749 CUIA axwiUMG X OA AMLUAU 7289 AGiC7r C AG7GACA 3723 6750 UMMA CaXPIM X OIA AG33r 7290 AC03 C IGOO 3727 6751 U0a CUAU(tG X MAA ACGAO 7291 Oi'rC7 c 3O 3738 6752- -=J6= amc x ai ax 7292 CACMr A CAOA 3800 6753 CUM=~ CUVJA X C G 7293 ui~gir C C3;M 3831 6754 tUrXXL CUAUGW X COA A~omom 7294 AGG0T A TCA 3833 6755 axxxuou CUCAUi2 X 03A AUAO= 7295 GAO C AGCAA3 3846 6756 GL0O3Gaumrr x a2 LM 7296 AAG= A =0MA 3852 6757 UUXXI= CLI1P]M X OM A0333 7297 AM=t~ C CCAAAA 3865 6758 cuwjp= CUx X GA AU~aXxz 7298 AAA=~ C GAIr.A 3874 6759 U3U3 CUALM X COAAGUt 7299 GAAG= C OCC 1 CM 3886 6760 UUAmCUxIxzG X C3A AGU3r 7300 AL I' C AACIMA 3907 6761 CAGLVI C 3A A=x 7301 AiX r C MCA=I 390 6762 AAW i X CcA AUM 7302 ACM=~. C AC7=I WO 00/61729 PCTUSOO/09721 Table VII. Hammneri. Ribozyrnes to CDP 138 3918 6763 ALGUM=lX CMflALmG X CA ACU G=u 7303 CAW=r T CCACAr 3919 6764 MUMJfl CtiaXM X CMA AACCAGU 7304 AACIF= C aCACMI 3927 6765 GACAcctI3 CtGAUGW X CZA AGJfLU~r 7305 CCCAAr A CAW=ct 3933 6766 dxK)CrSA CAM~AG X COA A~taflG 7306 anUC71 C Icm=a 3935 6767 G .L~p axwjmI X CMA AtGflJ 7307 ACAG=t C GxAa= 3940 6768 trttt= cCALIA X CGA AL~ar~ 7308 TC733A C COAGG 3954 6769 ccua',i ctflAuflAr. x a AmG=~l 7309 ACI= T CAT1kG 3955 6770 trCtrIAM CMLUA X - CA AA00=t 7310 -CAAC=~' c A~mAIsA 3958 6771 ALXX=tECUGAGA X CMA ALIGACA 7311 criTr T G~AA a 3967 6772 CM=r arnumG X CIA AIUX)= 7312 @CAAT T CAO 3968 6773 CtC33u CTflAiflA X C1A ?JAIUJ 7313 ~ AAAr C A0C 3980 6774 aCUGO CUGAUC-A X OS.A AaC 7314 CC03Sr C AGf3tCA 4005 6775 CtA33J C~ru)AG X Oa.A AGLClf 7315 MOXCr C AC= 4011 6776 MOM=l Ctm-. x am Aax 7316 CrItAT C MCC 4041 6777 C3= WUGIGA X CIA A~W 7317 GCtMG C GCXG= 4113 6778 MOCttxa cUL~W X 0:;A AXMC 7318 GCkAr C IAGGM 4115 67-79 arirt' COMUGA X OMA AG;ILMX 7319 CCA=t C AG33AGG 4176 6780 mrarI c~m~M X CC;A AG7320 GtCrO C G3M 4263 6781 03Mrt= CUMXWAG X OMA 0 7321 CCO c (~cx-c 4307 6782 MCMAM C umG x K AA~3 7322 ACC A CI= 431.1 6783 C03= juS; t x K CPA A~apnm 7323 C3M C.AC3C 4353 6784 GJ~cc cflumuir x omA JC 7324 C~%C C C33 4407 6785 UannMX CLUALIM X CMA A~ 7325 GCCCAr C O~GCG 4420 6786 A030GA CIM1G K OM AGW=~f 7326 CAA T TI3= 441 6787 GA3 CUGrwxG X OA AAGGl 7327 tCW= T ITC 4422 6788 WflM= CtvxW.a x c:A AAarM 7328 @otrrr T 03C=t 4423 6789 GOGAG=cu CUGAG KccAA AAA=U 7329 AGrr-.rr C G1ttc 4429 6790 O~a]tG CUMW= X CXA A; 7330 TICGr C Tr., 4455 6791 ualX= axImL K CCA AGr- 7331 ~C1'3A C G0COC 4494 6792 tJ32LU= CmuGAGx~ am ~Acau~c 7332 03OLrA T GACAMA 4504 6793 COMxMn MMUMG X 03A AtXtLJ 7333 AACA C ATC 4507 6794 AGC3 CUAUGt x o:A ALXlT 7334 AGCA= C CA03I' 4544 6795 Cam aiawim am ~A==L 7335 APGAT A IMM 4546 6796 tUCEM= CXLM X CMA ALPLXW 7336 GAAC= C GAT3 4557 6797 CCar aUMUMG K C~AAa= 7337 ;a33~ T CIAG 4558 6798 Gcamuc cumucG x a AILxxr '7338 703A C 7GG 4618 6799 cxtii:;t cuA~jM K 0:i AOa 7339 GA33r C GGC 4656 6800 03033 CUGAUGiG X OA AGOY 7340 CII' T C-M" 4713 6801 Gn~Lt~m cuatmX~ K3A AM3r 7341 G; C1T c M,3 4720 6802 AG0 CUPIGA K OMA ACO1S 7342 MCA= c 033= 4750 6803 033CCE CtAUA K 0:A AL10 7343 GCM C CAA13= 4774 6804 G3000 CUPIGA X OA AG103 7344 GACC~ C G3 4801 6805 cGUiG= CtX-.AGA K CCA AG303 7345 TG3X:C CACAC 4853 6806 AGO =70GtG K CIA AGO 7346 GGO T 7000AC 4854 6807 AzA~uo cuxN;G K CiA A~aX= 7347 GACO= T G0Crr 4862 6808 A0= cumimG K C)A AGI33 7348 TG0c~r T ACOOr 4863 6809 CA3 c~uim K c:;A Ala 7349 GCCCT A C03IG WO 00/61729 PCT/US001 09721 Table VII. Hammett, -Iibozymes to CDP S139 F4889 6810 ccum ctrALr.G x cA ALUUt= 7350 GCArA C OCAA 4895. 6811 Ct'UUfXC MAUMGi~ X CGPA XAtDAU 7351 -A03 A GQXCA S4909 6812 XMtItt-. C-MUGAGl X GZPA 1AC= 7352 A~GT A TAA 4911 6813 LUt1Mut CLU~r-A X 0:A .4MIXXJC 7353 G'GCM A GAAAACA 4928 6814 ULtmMzu aiGuGAG3 x c:A xiatI~u 7354 AGGA= T A~AGCC1 4929 6815 AUJUMU MUGDI X CC;A AXmrc 7355 G~vA3 A AGCCA 4938 6816 ACOC- CtM)GA X CCA AUtU3 7356 AGCCA C MIwr 4940 6817 JACAMAM CMUAG~ X COA AGUU33 7357 CtCAATr A ~IGICO 4944 6818 GAAAD=-C arAM-Pr. X OMA AM[MIJ 7358 A==I~ C GI7ITrrIr 4949 6819 ttCUtCPA CXLrAL7JP X CA~A ACCGC 7359 I70=~ T TCAAM 4950 6820 tUCMM aXALMG X CMA AMOC 7360 G03=~I T MA~AGA 4951 6821 CUJCC= un inw x a:-A AA)c~mA 7361 T'i16=r T CAAGAA 4952 6822 tmtttOu cfLrAI3A x cmA AAaAAcr 7362 acmi 1rr c A?~A~c~ 4978 6823 AAAAG=~ CtAUGA X C3AA ALACC 7363 IuI7IGI C C4Nrrr 4984 6824 GLMAAAA CAMA X aMA A~aXXAC 7364 GICQZ= T TrI'I= 4985 6825 GGLACAAA aC-UGAG X O:A AA = 7365 ICCIT T MGM", 4986 6826 G0CA-A anr-,LG X OA AAAGCU0 7366 cSArr T MGM 4987 6827 J*GMMO CMUMiG X CMA AAAI= 7367 GAOHiTT T TGLMr 4988 6828 CA3L, Ctfl~umG X CMA AAAAAGCU 7368 AGCITI T GrACG 4991 6829 CLUx2 CLUMMI X CA ACAAAAA 7369 'TI'Irr A CLITUW 5003 6830 .AAAAAA CAUGW~ X O:A AOX~ 7370 TGAG~r T 'I'IITra 5004 6831 AALWAAA ctrvImG x cGA A~c!X= 7371 GAIGr T TrI=~ 5005 6832 CAUA CfL7ALr-,P X CGA AAACACOJ 7372 AAGIG=~ T TrTfM=I 5006 6833 GM~AAM CXGxUM3 X CCA AAAA=C 7373 AGIGI=~ T TT1= 5007 6834 GOCAUA CUGAUGA x aMA AAAACA 7374 GII= T TIAd'I 5008 6835 G3CA~ CUAUA X CA AAAAACA 7375 'IG~i'i*r T VIa'I= 5009 6836 AG nA CUGAUM X K AAAAA 7376 GITrrr T A'IrGi 5010 6837 UAGOMA CUAL1MG X CGA AAAAAAAA 7377 TrIrT A TIGC] 5012 6838 CUAGO CVGMtCP X 0A AMAAA 7378 TrrrA T GCOCMA 5018 6839 AAACPCU COGAUSAG X OMA ~AO 7379 A7ITW= A LtAGT 5025 6840 CaU~ CtLIGM X CA NtAUta 7380 IAPAI= T ICCA 5026 6841 ACCflf CLGUA X COA AAUJ 7381 AAG7=T T OMC 5027 6842 AA:flf CLMB x =A AAADU 7382 AGIGAr C CAM= 5035 6843 UAULCrA CGALIGA x a3A ACtaflfl 7383 CCCAn T MOGAM 5036 6844 . tXPLXA arjcG x a -A~t!fl 7384 CAM C 70AM 5043 6845 GUAGG CIALtX~ K A AUIXk~ 7385 T'IGCNWd A CMTMIC 504 '7 6846 AGC ummw x K c A uA 7386 C MCA= C 5049 6400~l U 3 A X~J 78 ~~~t ~I 5050 64 ALnaIp ~ 38 T~trA@I 5072 684 AO XUA Xui K C AGA 7394 AiTitr T AGI't 505 85 CViK A 739 7ACAGLT T TIUI= 5076 6856 C3AAA CtMI X CG AGGC 7396 ItII C IGI= WO 00/6 1729 PCTUSOO/09721 Table VII. Hammer. Ribozymes to CDP 140 5087 6857 UrUA CurALIJ'. X CMA AGCC.P 7397 IUG= T ThAA 5088 6858 ut-7Xuuu CUXr.Ar. X OSA AAGCCC 7398 G703=r T AAAGA 5089 6859 uuutruut C~AMPC- X CMA AAAX=~ 7399 'IGI3 r A AAAAAAA 5103 6860 GU3GMJU Mr.AMXG X MA ?IUUUUUEJ 7400 AAAAAAAT c AAACC 5114 6861 CaCUJtA CUMLAL X CIA AUGX3= 7401 ACtCACAT A T I' M)A 5116 6862 ccctvmu mrimcJ x apA Atfl= 7402 CCATT T AAAA= 5117 6863 CCCtCUUEJj c~rlmpr, x CtA MtAL f 7403 CACrr A AAAGXX3 5128 6864 CAA Car-4iJJv. X CMA MrC= 7404 AG33=~~ T TIM%= 5129 6865 OCAALMA aLXX)P X CMA AA3C 7405 G333 T TkI= 5130 6866 G~;GL C~An C-Ar X O:P AAG 7406 G333= T TATI= 51-31 6867 UxxX3CGU anO~p X 03AA AAAG= 7407 G33=t~ T ATC=r 51-32 6868 AUXD2ALA CLUAtrnA X CM MAAAWDC 7408 -rrrrr A TCG 51-34 6869 AGAOflM anir- z x cmA AIJAAAAPL3 7409 cITIT c C = 5141 6870 pAOxCMM CUALM X 02A AMCA 7410 'TICTG C TAT 5143 6871. GCCAU CtA~rAG x a2A Aaxick 7411 TOM=t A ArTGri 5150 6872 MtOM=~ CMMAG X CMA PMCAM7L 7412 AAr T CAAC 5151 6873 AUCtt MMUMG X CIMA A1LAGCC7EJ 7413 AAnrr C COXA 5160 6874 UkLO crwm x cGAA AIU03 7414 ACAGOCAT A ATACC 5163 6875 UAAI=f caur-.A X CSA AIJTW I 7415 OTAMAT A CAIA 5168 6876 CGAfLMp cuioi X CC~A AGi t 7416 AAT1C=E A TrCAIC 5170 6877 AAAGMn CU~p X 0:;A AULGl 7417 7AC%= T A~TIr 5171 6878 UNAa cumUGAG X C:; A AA3~aM 7418 AC.Tr A Writ'r 5173 6879 UUtAAGA cumum x cA Atpxpm 7419 Am =T~, c Ticrn;AA 5175 6880 GOLUDLAG CLAU X OMA ~IAGUA 7420 'T r T CIAAAC 5176 6881 UGGLUXAA cuwxm x a2A A~aimmA 7421 ATtT= C TEAMk 5178 6882 Can=~u cVMiMG X 0:A A~kflA 7422 U7UCI'Mr T AAC 5179 6883 UCCULJ CGAtM X O:A AGAAGA 7423 ATCr'tT A AACCGt 5194 6884 ~COCC= CLXKzXW X 0: LX 7424 GAAAAAT A AAG= 5211 6885 ULUttAA ctXGAUM X OC;A ACC= 7425 GUC3A T ITICA 5212 6886 UutaxPA c nu~cw x am xx~ 7426 GIG3=T T TIAA 5213 6887 uutmI= Cumucw x cmA AAAEm 7427 1U.Trr T TCAGAAAA 5214 6888 UUUUUw~r CGAIxMG X MIA AAAIt 7428 CGTG IT T CAAAMA 5215 6889 AUUUUtnLJ CtUGAG~ X CM AAAL 7429 MAT=r C AGAAAAT 5224 6890 tuCUUtmj CIAL10AG X CGAA ~AM =r 7430 ALGAAAAT A AAAAA~ 5237 6891 GacA qxwn~ x om axi~ 7431 AAA T TrIMG 5238 6892 Acam axmuc2 x a ALa=t 7432 AGAA=I T TIGIAG= 5239 6893 a~cmc CU.-VjG X 0;A AA~LX= 7433 GAAIVIT T T~G7A 5240 6894 ACGA CtUiX X OM AA 7434 AAIT= T GAG= 5243 6895 UGAC CUCtICW X OMA AAAAC 7435 GTFIr A 071G='~ 5249 6896 GCl2Ctf LGAL1MG X CM CGM 7436 arIMG r T CAGT= 5250 6897 UGOMAU CUGALGA X OM AAAC3 7437 TIA I'r C AG1'tk 5254 6898 UrV;G CUGUGA X CMA ACGA 7438 TG~riX= T GCC~AC 5261 6899 aAtU= CtXAIMG X OA AG13A 7439 TIGOCT A AGG 5268 6900 GCU=nj CUGAWA X COA AMtU= 7440 TAAAGT T CA~C 5276 6901 @w4 uuu CUAUGAG X CIA ACIL1C 7441 TO~.~ C AAAACI= 5284 6902 UG~aXXA CtXM7G; X CSAA AGUUxxn 7442 CAAAACT C AAAM 5286 6903 Aau=t CU~ X 03% AGAG 7443 AAAA=I~ A A!I7C WO 00/61729 PCTUS00109721 Table VII. Hamnmeri. Ribozymes to CDP ______ _______141 5295 6904 AUtLMW CtGAflPG X CGA AGU~aU 7444 AA~CACr A GIITM3AT 5298 6905 GGAACC CLISAMtX X OA AMC=f 7445 ACACM~r T MCA=rr 5299 6906 AGGAACC CMUAG~t X CA AAt19=f 7446 CA~nrr T GGM=w -5304 6907 nUUXXP CUIr.A X CXMA AELCAMAC 7447 GI=~. T CCIAAn 5305 6908 AIUtXUN CtXUflAs X OS AAMC~AA 7448 j'ITG= C CIAAMT 5308 6909 AAAAtUiLu CtUMZG X crA ~ASAL1C 7449 -GT1Wr A AA7f= 5312 6910 CLXXPAZA CMfLUD 3 X OMA AUXPL 7450 ~ TCMA~A A T mrrAA .5314 6911 UUCtLUA CtLUMPGl X C3A AUUX 7451 CAAT T TIIVA 5315 6912 LXXrurM CMAMAG X CMA AAtMIUM 7452 TAAA=~d T ICAGA -5316 6923 UUUXICW CLtGAMA X OM AAAIA=UE 7453 AM=~'r T M~~AMA .5317 6914 CUtUtXLUr CtGAMAG X 0C@A AAAAUAWX 7454 AATiATrrr C AAAAAAG -5329 6915 AAGGA CMflJIXO1 X COA AIJUflUUUU 7455 AAAA% C 'rICICGI 5331 6916 CAACA CtGAUA X 03AA utruuI 7456 AAAT T CiTrri 5332 6917 UAAC CUAUGA X QGAA AAIXA 7457 AGArr C TI , .5334 6918 LX17MW CLGAM X OMA AGAM 7458 -AA~Tzw C GarIGA 5337 6919 AAGUUUC. CGAMA X CMA A0A% 7459 _%IWII T IAMQI .5338 6920 AAGUUXC CUfAGA X CrA AAGGA 7460 ICI=I T GAACI'I 5345 6921 MPAIXM CUGA=G X CA AGUM 7461 77GAAACr T 'IGAkTA -5346 6922 ULTXAIX= CGUGLG X CMA AAGUXIC 7462 TAAACIT T GAA -5351 6923 uutXMjUUU CUMUiG X 03A ALXMA 7463 CrMIMA T AAAAAA. -5352 6924 UULXML.TUU CUGAXPG X CA AAUUCAAA 7464 TIIGATr A AAAIA 5357 6925 AUGGIX~J CULAMM X MA AIJUMPAI 7465 ATMIAAAT A AACACT 536 6926 GLOAGI CLXPUA X OMA AUOU=J~ 7466 AAPMP T 'ICC 537 6927 UGUGGAJ CIA~IX2 X MAA AAM~U 7467 AAACTr T ACICC 538 6928 CLUU0A CUALUA X CGA AAAGUOU 7468 AMC=r A CICCA Where "XC' represents stem II region of a fIN rbozyme (Hertel et al, 1992 Nucleic Acids Res. 20: 3252). The length of stem II may be 2: 2 base-pairs.

WO 00/61729 PCT/USOO/09721 142 Table VIII. Sequences for controls & Hamnerhead and Hanimerhead-like Ribozymes SEQ. I.D. Sequence ND. Numenh 196 14240 cccc ctGAnGa C ' ccGaa Agca B 278 14244 g u ctugac cG aggccguuaggccGaa Auuugca B 204 14252 g-c,1sgugc ctnGaqgccguaggc cGaa agug B 281 14260 C- C-c Aaggugg B 3581 14336 gcaqusg - c aAuGa C-"tnggc-aa Auuucuu B 3504 14341 gcT gaa cUG uGaggecuuaggccGaa Auuuuuc B 4993 14437 gg ccGaa Aacuuuu B 5090 14452 cccaa Agucg B IR1 13196 c a c cGAuGaggccguuaggccGaa ACgagac B IR2 13201 gcgccaggcu cUAiGagcI qa9aGau Aaugcgc B 6929 c c uucu ct2AuGagqc cgccGaa ICUCUUC B 6930 CCmUXCC - aggc fgacGa Iccuucu B 6931 u.agga c C ra B 6932 ugca,gcu ctAuGagccguuagg aa 6933 9MAmaa__uau__r 6935 gac.auu ctCAuGaggccguuaggccGaaugaac B 6934 __ uccuauce ctEAuGaggccguuaqgccGaa Iucc B 6935 ungcuuag c iuaqqccguuagccGaa B 6936 _________ 5!IgrcAPIaggccquuaqccGaa guc c B 6937 agcuugu w cAuGaggccguuaggcAca 6938 cgsgSggA ctEA!aggccguuaggccGaagugaa B 6939 wa~guaga cAGaggccguuag aa Ica B 6940 cguua ctAuGaggccgmo aac I a B 6941 ggagga cAGaggccquuaggccGaa loxcag B 6942 gg.ggu cAuagccguuaggccGaa Iugug B 6943 caggcau cUGAuGagjgccguuagccGaa iaa 6944 cuUqgacq c Guagccquuaqcca Ia B 6945 g.Cqcc c:: aBcquqqca 6946 9Ju,.acc cAuGagccquuaqccGaa Iccctm B 6947 cuuccu ctuaccquuaggcG Iacccag B 6948 4Ju14ge cqGAuGaggccguuaggccGaa Icqua B 6949 gggguga c agccguuIgaggcc B 6950 crac~gqu cUG Caqq cgcquqcg B 6951 -caukagg cinAuGagccuuaqqccGaatltni B 6952 a,u6aau c G aq uaq a B 6953 ckcawqcu cMGuGaggccquaqqccGaa Lacgu B 6954 acru~gqcc ct.aqLggccuuaggccGaa Iuuaaca B 6955 agg.uggu CtuaggccguuaggccGaa IUK B 6956 c-as,.c.C cTflAaggccquuaggccGaa ggu B 6957 ga.ggg__ ctMuGaggccguuaggccGaa_ 6958 guc.a.cca cYG uGaggccguuaggccGaa Icgac B 6959 cugg ct7 uMaqccquuaggccGaa IgcgLg B 6960 cag.cauga ctUaggccguuagccGaa I B 6961 caac,agu cr uagccguuaggcc aa 6962 U.qMIuu 9!X Iaqgc gn gccaa Iucucu B 6963 qngawqu ctUGaggccguuaggcc aa Mtuc B WO 00/61729 PCT/USOO/09721 143 Table VUI. Sequences for controls & Hammerhead and Harnmerhead-like Ribozymes 6964_ cgaag ct;A aqgccguuaggccGaa Icuqcuu B 6965 . . _ . uuuqa ctrAuGaggc.cguuaggccGaa Iugcaau B 6966 g.c~ug~cuc cUGAuGaqqccguuaggccGaa Iuaacaa B 6967 aa.u,gaac cUAuGaggccguuaggccGaa Icuugcc B 6968 aau~ccuu cUGAuGaqgccguuaggccGaa Icagccu B 6969 a,gag.ucu ct3rAuGaggccguuaggccGaa Icuucau B 6970 __uucaaug ctCAuGaggccguuaggccGaa Iuuuucu B 6971 cu~ucaau cDGAuGaggccguuaqqccGaa Iguuuuc B 6972 ac..uucaa ctGAuGaggccguuagccGaa Igquuuu B 6973 accu.ugga cUxlAGaqqccguuaggccGaa Iauuuuu B 6974 cacaguu cIAuGaggccguuaggccGaa Iaagauu B 6975 gc;acagu cAuGaggccguuaggccGaa Igaagau B 6976 uu~g.a.agc ctGAuGaggccguuaggccGaa Icacaqu B 6977 utuLuujuuc ctIkAu-agqccuuagccGaa Iuuqaag B 6978 a.,u,gcccu ctGAuGaqqccguuaggccGaa Iaaacau B 6979 uutgcaag ctUagccguuaggcGaa Iugucaa B 6980 a~gagaa ct3AuGaqccguuagccGaa Icauqqu B 6981 ua,ggaga ctAuGaggccguuaggccGaa Igcaugg B 6982 ggxuacuc cUGAuiaggccguuaggccGaa Igcauag B 6983 uaaqaac ctXAuLGagccguuagqccGaa Icaqucu B 6984 Mac caag cTiAuGaggccquuaqqccGaa Iuaaaaa B 6985 ca.gcacu ctC-AcgccquuaqqccGaa Igcaaga B 6986 acuiug=c ctiAu-aggccguuaggccGaa Icacugg B 6987 u,ua cUGfuaqqccuuaggccGaa Iucucc B 6988 cc.acaua c AuGaqccquuaqqccGaa Iccuuuu B 6989 a,u,a,a,ucu cDGAuGaccuuaccGaa Igaaunc B 6990 qccaaug cDGk.aim ccuuaqgccGaa Iaccuuu B 6991 uugccaa cUGAuGaqqccguuagccGaa Iagaccu B 6992 aNuciugca cDAtaggccguuaggccGaa Icuccau B 6993 c__ uac.cau ct 3aiccquuaqqccGaa Iccauau B 6994 ciucgaug ctGAuGaccuuagccGaa Icugcug B 6995 cacucqa ctXGAuGaqccuuaccGaa Iugcugc B 6996 __ ccacu c Ai.aggccguuaggccGaa Iuccccq B 6997 ,uaauu cUGuGaqgccguaqgccGaa Iccquag B 6998 ucg.caq conaggccuuagccGaa Iaauuq B 6999 c,,_ uuuge ctXAuGaqqccquuaqccGaa Icccucq B 7000 cucuuga c ArgqccuuaggccGaa Iaaacuu B 7001 uaa,guua colraqgccuuaqccGaa Iuuccug B .7002 auqju~gua ctLAGaqccuuagccGaa Iunaagu B 7003 cggcaug ctLGagccguuaggccGaa Iuaagun B 7004 _uc.,cugu cp inaggccuuaggccGaa Icacqqc B 7005 cagquucc cUtiAuGaqccuuaccGaa Iuugca B. 7006 ___u,,g. cu ctXAuGaqqccuuagccGaa Iucgaug B 7007 uucu uga coArggccquuaggccGaa Icqqcaq B 7008 actpuuga colAjnaggccguuaggccGaa Icacuuc B 7009 gg,14uugqa c GaggccguuaggccGaa Icanncu B 7010 gracagu cP3AuGaqqccguuaggccGaa Icaguqq B 7011 __u. ~uq.uu col ngccquuaqqccGaa Icugca B 7012 ac.,u1cgac cLX3AiaqqccguuaggccGaa Icgcuqa B 7013 c.,a cga.,ucc ctGAuGaqccguuaqgccGaa Igaagaa B WOO00/61729 144 PCT[USOO/09721 Table VIII. Sequences for controls & Hammerhead and Hammerhead-like Ribozymes 7014 a_____~ag. u= cXGAuC-A-- wtaggcc~aa Iaugqu~ B 7015 _______ ,.cgau SLXrAGaggccguuaggccGaa Icuuuga B 7016 !,CaqGiagcmm9ca g= B 7017 ________ u gggt 5;U AuaggccguriaggccGaa Iuacugg B 7018 C.U~g g.IUt1 cUAu~aggccguuaggccoaa Iguacucl B 7019 cgaugac ctflAiGaggccguuagcjaaIa B 7020 9,9 L4 tflqAuGaggccguuggcccaa Iuuucga B 7021 atugg~aca cUGkiGaggccgujjaggcC~aa Iuwagc B 7022 axcjuggau ctXA1.~aqqccgtnjagcccaa Iacauqu B 7023 aug UkaccguaqcaaIaacB 7024 t~cctuaaa ctXAI.aggccguuacmccGaa lagucuc B 7025 cciu~uucu cUGAuaggccguuaggccGaa Icuctaic B 7026 C.~C.u 1CCC LtXE3 2ggcguuaggccCea Iccuucu B 7027 _________ cGAu agc~cguuaggccGaa Igugga B 7028 ______ 'gcagrcu dctAC~aggccuuaggccGaa laugB 7029 ______gaqcam~ Ct AGaggccguuaggcc~aa Icacaac B 7030 _______ .~CJc.UCC cL agccguuaggcccaa Iugaccc B 7031 ugctuuag ctXiIAggccqiuaggccGaa ;qtaa B 7032 i4L .acau ctflAuGaggccguuagccGaa Iugcagc B 7033 agcuutgu ctrAuGaggccguuaggcccaa Iuaga= B 7034 ______acgggug ctAuaggcCgnaaggcccaa Iggugg B 7035 uagqiuaga cMAuaggccguuaggccCaa Iccacacr B 7036 ctu~gc.uia cUG GaggccguuaggccGaa Iggugada B 7037 gggg cUCAuGaccguuagcc~ea Icuggag B 7039 cqagggg cUGIflaggccguuaggccGaa Icacam B 7040 c_____ a GtAv~aggccguuaggccaaa Iccgg~ B 7041 _______ q gcc gCuGaggcc9Uuaggcccaa Igggu B 7042 gju.accc ct ~iaccguagc1aa Icccuuc B 7043 CucUq cUG uaggccguuaggccGaa Iacccacr B 7044 a,____ guugc cUGa~ccgagccGaa Iocnigua B 7045 _________ dUGtA. aggccguuag~cca Igaggcc B 7046 ______ acsgvu dctGagccguuaggccGaa IT99-9 B 7047 ______caj~aa. cU Lr.-jgccguuagcCc~aa Iuginm B 7048 _______Aaaggu CUQ~aggccguagccGaa AK9-ig B 7049 cc,___u ______quag___aIagm 7050 ___ __a,4u.g'. cY kI 9CCquuagcccaa lumaaca B 7051 _________ cY 1flagccguuaggccGaa IigLu B 7052 _____________cuugqc~a aggg 7053 __________ cUk~gcgua9ca c 7054 ______gcAgcca ctrtagccguaggcca Icggac B 7055 ________ ~ tA~ag ccguuaggccaaIc~ B 7056 caua _r___9______aaIguga 7057 ______ccapu cUG uaggccguaqqCcGaa Tacacac B 7058 ___ __ucjgjq~ggu cflA. agcguuaggcccaa Iucgucu B 7059 gr~agcuq ct uGaggcguaggccGaa Igc B 7060 _____ _q___ U~jagcgmgcaaJaa 7061 _________ c3Ai~eggccguuaggcccaa Iucaau B3 7062 ___ __gcugcw cUaggC-cc.nam~ccGaa Iuaca-a B 706 ta~ugaac c3A.Caggccguuacgcaa Iuugcc B WO 00/61729 PCT/USOO/09721 145 Table VII. Sequences for controls & Hammerhead and Hamrme rhead- like Ribozymes 7064 aai:z~ ctX AuGagcc c a Icc 7065ucuCUAul cc agccGaa IcuucauB 7066 __________ c klgGac gugccGaa Iuuuuucu B 7068 CL1 -aa ctGAuGagcc cCaa Iq~n B 7069 caa____ ctrAi~a cc CcGaa Iauuuu B 7071 C ctXq u a cc c~aI u 7072 a acC gcgugc Iauuau B 7073 Sa,~~uu ct ;a 9C 99ccGaa Iauu B 7074 gu~c, ,au 'U~A aggc gugc~ aaauB 7075 ~ g c! ctfAx.~a c ccGaa Iauq B 7076 _____________rc~naqrc~a Iugac 7077 - C - c U C C U a 9 c ~ L M c a a a a 7078 ugcaagj c7MAGagc~ 3cc a Icaucaa B 7080 Z-,.-ca cUAuv-agqccuuaggc~a Iuaa B 708S.4 ___I__ IagCac StflAixagua ca Igcaaa B 7082 _______ c~ugaac Ctruagccguuaggc~a Icacu B 7083 ~s p ~~~ag C-I . 7084 cLtg c S C M~j g c a c c g 7085 C.acaua St aCIgU aggcc~a ICCauu B 7086 N.. caac cUGAu iccguuagcca Igaci B 7087 u9.ccaa U2Au~aggccguuagcca Iaccum B 7088 ~u~cjucaa cUAu accccjuaggcc~a Icucc B 7089 ac.ca~ cEIaG Ccggc~a Iccuau B 709 w_____ 5-qau CE! LaggCctjgc Icccug uB 7091 ______cau ct al'ccguuac~a Iucug B 7092 cgruIUuagcgagcaaIccLfA 7093 gtgau E ca Iccguacg B 7094 t~g.. ctUnCagqcgu~aa Iaauucx B 7095 cjujugc qU~uGaggcC9Uuagc~c~a IcCCUccj B 7096 W49~ugau c hacC9Uuagqcca Iaaaciii B 7097 __,!___ uan,~ ta~guuaSGggCMM9craa Iuuccuir B 7098 _____ au~qgum cUG Jaggrccquuag~ccxx Iuuaagu B 7099 _______ caug !T"Azsaggccqtnaqca Iuaaqui B 7100 ________ 'u gu 2U - ccuuagc IcacggcB 7101 ____ _caguu. CVGAu aggccguuaCgc~aa Itn.mm B 7102 ______*qg.U.t cUCAagccguuaqqcc~ Ia at B 7103 tqu___ _Gu______gg_~a cgca 7104 ____ acuugu ctr!ag~c gagccaa Icauuc B 7105 cr________ LIC C guagca Icaucu B 7106 gaau __u__g_9_____~a ca= 7107 t______ pu.ugui cUt Gagccgtniagcc Icuca B 7108 acAca LU-za~pj~gc I~cgca B 7109 _____Cagqa.~UCC cp~~ggC guagc Igaagaa B 7110 4^g___ agct C! ~agc guaggccGaa Iaugugg B 71n1 _____ 9.qc~agau cLr Gagcpguuagc~a ICUU.iga B 7112 agag cUCAagccguag~cc~aa ICUUL9 B 711 ______ugu~ Gcguuaq gccgaa at B WO 00/6 1729 1 46 PCTIUSOO/09721 Table VIII. Sequences for controls & Hammrerhead and Hamnmerhead-like Ribozymes 7114 c.u49g9guu9 CUGAUGaggCCng ~a Iguacutr B 71.15 ___ __c.q..a.Lucgac CLM3agcCSUgg~ccaa Iaggagg B 7116 mm--a rcU-allAeggccguunaggcc~aa Iuuucga B 7117 ____________ccuaqccGa Iaalq 7118 a-gc 49qgaL cUGAi~aggcc9UUaggccjaa Iacaugu B 7119 qA,49 cTXA[aggccguuaggca -Igacaug B 7120 u_______a UC____cuugg__a agcu 7121 agtuu CAU~aggcciuaggccGaa Iuagagg B 7122 Cug.cuua cUAuGaggccguaqgccGaa Iggugaa B 7123 _________ a cjUGAGaggcc9UUaggcccaa Icuggag B 7124 9.a.g.9g9u cUAtCaggcCgtniagca Icugugg B 7125 u L1.c ct CGL~3agccguLaggcccaa acccaq B 7126 9...gg qct aggccuuiaqccGaa Iqaggqcc B 7127 9..99u cUGAuGaggccguuaggccGaa Igu B 7128 Auaagu cUGiuaggccuuaqqcccaa ugguug B 7129 CqtqugGuag~uagca a~ 7130 gac;A c McAuGagccgmkuaccGaa Ig=-c B 7131 aiti~g CtX~AGaggccguuaggcccaa Iauuuai B 7132 t~ugaac c UGCa~gguuagqgCaa Icacaqu B 7133 c~CAgc.aua cUGtiggccguuagcca Iccu~um B 7134 c~t~ctugta cUC4W-aggcCguagqccGaa Iaaacuu B 7135 ______ ctucgac cA1Ga~CggUaggccGaa . cgcuga B 7136 4^.ug c t~gccguagc Iau~z B 7137 agctg qCT uaggccguuaggca~aa Igcuuuct B 7138 c~..4g U ra c a g B 7139 axig cUG uarJccguuaggcccaa Iacai.gu B 7140 ______ ii:aaa cZ1IaG~ccguuaggccaaa agucuc B 7141 ______qc~ccaccuc Ggaggaaacucc aj aCAGAAXLuCG B 7142 gjugu.c WU,2g gafcuug g auaucuacc B 7243 ______a..ugc uGAU,2gq ca~cacuaugu ga auaucuut= B lower case =2'OMe U = 2'-C-Allyl-U GA U= ribo GA U S=phosphorothioate linkages S2=dithioate- linkages B = inverted abasic l=ribo-lnosine

Claims (10)

1. A nucleic acid molecule capable of specifically inhibiting expression of gene encoding TR2 Orphan Receptor.

2. The nucleic acid molecule of claims 1, wherein said nucleic acid molecule is an 5 enzymatic nucleic acid molecule.

3. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule is an antisense nucleic acid molecule.

4. The nucleic acid molecule of claim 2, wherein the binding arms of said nucleic acid molecule comprise sequences complementary to any of sequences of Seq ID 10 Nos 4172-4950.

5. The nucleic acid molecule of claim 3, wherein the nucleic acid molecule comprises sequences complementary to any of sequences of Seq ID Nos 4172

4950.

6. The nucleic acid molecule of claim 2, wherein said nucleic acid molecule is in a 15 hammerhead motif.

7. The nucleic acid molecule of claim 2, wherein said nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid or RNase P nucleic acid motif.

8. The nucleic acid molecule of claims 2 or 3, wherein said nucleic acid molecule 20 comprises between 12 and 100 bases complementary to RNA encoding the TR2 Orphan Receptor.

9. The nucleic acid molecule of claims 2 or 3, wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to RNA encoding the TR2 Orphan Receptor. 25 10. The nucleic acid molecule of claim 6, wherein said nucleic acid molecule comprises any of sequence of Seq ID Nos 3393-4171. 11. The nucleic acid molecule of claim 2, wherein said nucleic acid molecule is an enzymatic DNA molecule. 12. The nucleic acid molecule of claim 1, wherein said TR-2 Orphan Receptor is TR2 30 11 Orphan Receptor. 13. The nucleic acid molecule of claim 1, wherein said TR-2 Orphan Receptor is TR2 9 Orphan Receptor. WO 00/61729 148 PCT/USOO/09721 14. A nucleic acid molecule capable of specifically inhibiting expression of gene encoding EAR3/ COUP-TF-1. 15. The nucleic acid molecule of any of claims 14 wherein said nucleic acid molecule is an enzymatic nucleic acid molecule. 5 16. The nucleic acid molecule of any of claims 14 wherein said nucleic acid molecule is an antisense nucleic acid molecule. 17. The nucleic acid molecule of claim 15, wherein the binding arms of said nucleic acid molecule comprise sequences complementary to any of sequences of Seq ID Nos 5248-5544.

10 18. The nucleic acid molecule of claim 16, wherein the nucleic acid molecule comprises sequences complementary to any of sequences of Seq ID Nos 5248

5544. 19. The nucleic acid molecule of claim 15, wherein said nucleic acid molecule is in a hammerhead motif. 15 20. The nucleic acid molecule of claim 15, wherein said nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid or RNase P nucleic acid motif. 21. The nucleic acid molecule of claims 15 or 16, wherein said nucleic acid molecule comprises between 12 and 100 bases complementary to RNA encoding EAR3/ 20 COUP-TF-1. 22. The nucleic acid molecule of claims 15 or 16, wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to RNA encoding EAR3/ COUP-TF-1. 23. The nucleic acid molecule of claim 19, wherein said nucleic acid molecule 25 comprises any of the sequences of Seq ID Nos 4951-5247. 24. The nucleic acid molecule of claim 15, wherein said nucleic acid molecule is an enzymatic DNA molecule. 25. A nucleic acid molecule with RNA cleaving activity, wherein said nucleic acid molecule cleaves RNA encoded by a GATA transcription factor gene. '30 26. The nucleic acid molecule of claim 25, wherein said GATA transcription factor gene is GATA transcription factor 2 gene. 27. The nucleic acid molecule of claim 25, wherein said GATA transcription factor gene is GATA transcription factor 3 gene. WO 00/61729 149 PCT/USO0/09721 28. The nucleic acid molecule of claim 25, wherein said GATA transcription factor gene is GATA transcription factor 4 gene. 29. The nucleic acid molecule of claim 25, wherein said GATA transcription factor gene is GATA transcription factor 6 gene. 5 30. The nucleic acid molecule of claim 25, wherein said nucleic acid molecule is an enzymatic nucleic acid molecule. 31. The nucleic acid molecule of claim 30, wherein the binding arms of said nucleic acid molecule comprise sequences complementary to any of sequences of Seq ID Nos 1-1696. 10 32. An antisense nucleic acid molecule capable of specifically inhibiting the expression of a GATA transcription factor gene, wherein said antisense nucleic acid molecule comprises sequences complementary to any of sequences of Seq ID Nos 1-1696. 33. The nucleic acid molecule of claim 30, wherein said nucleic acid molecule is in a 15 hammerhead motif. 34. The nucleic acid molecule of claim 30, wherein said nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid or RNase P nucleic acid motif. 35. The nucleic acid molecule of claims 30 or 32, wherein said nucleic acid molecule 20 comprises between 12 and 100 bases complementary to RNA encoding a GATA transcription factor. 36. The nucleic acid molecule of claims 30 or 32, wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to RNA encoding GATA transcription factor. 25 37. The nucleic acid molecule of claim 33, wherein said nucleic acid molecule comprises any of the sequences of Seq ID Nos 1697-3392. 38. The nucleic acid molecule of claim 30, wherein said nucleic acid molecule is an enzymatic DNA molecule. 39. A nucleic acid molecule capable of specifically inhibiting expression of gene 30 encoding IRF-2. 40. The nucleic acid molecule of any of claims 39 wherein said nucleic acid molecule is an enzymatic nucleic acid molecule. WO 00/61729 150 PCT/US00/09721 41. The nucleic acid molecule of any of claims 39 wherein said nucleic acid molecule is an antisense nucleic acid molecule. 42. The nucleic acid molecule of claim 40, wherein the binding arms of said nucleic acid molecule comprise sequences complementary to any of sequences of Seq ID 5 Nos 5967-6388. 43. The nucleic acid molecule of claim 41, wherein the nucleic acid molecule comprises sequences complementary to any of sequences of Seq ID Nos 5967

6388. 44. The nucleic acid molecule of claim 40, wherein said nucleic acid molecule is in a 10 hammerhead motif. 45. The nucleic acid molecule of claim 40, wherein said nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid or RNase P nucleic acid motif. 46. The nucleic acid molecule of claims 40 or 41, wherein said nucleic acid molecule 15 comprises between 12 and 100 bases complementary to RNA encoding IRF-2. 47. The nucleic acid molecule of claims 40 or 41, wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to RNA encoding IRF-2. 48. The nucleic acid molecule of claim 44, wherein said nucleic acid molecule comprises any of sequence of Seq ID Nos 5545-5966. 20 49. The nucleic acid molecule of claim 40, wherein said nucleic acid molecule is an enzymatic DNA molecule. 50. A nucleic acid molecule capable of specifically inhibiting expression of gene encoding CAATT Displacement Protein (CDP). 51. The nucleic acid molecule of any of claims 50 wherein said nucleic acid molecule 25 is an enzymatic nucleic acid molecule. 52. The nucleic acid molecule of any of claims 50 wherein said nucleic acid molecule is an antisense nucleic acid molecule. 53. The nucleic acid molecule of claim 51, wherein the binding arms of said nucleic acid molecule comprise sequences complementary to any of sequences of Seq ID 30 Nos 6929-7468. 54. The nucleic acid molecule of claim 52, wherein the nucleic acid molecule comprises sequences complementary to any of sequences of Seq ID Nos 6929

7468. WO 00/61729 151 PCT/US00/09721 55. The nucleic acid molecule of claim 51, wherein said nucleic acid molecule is in a hammerhead motif. 56. The nucleic acid molecule of claim 51, wherein said nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid or RNase P nucleic 5 acid motif. 57. The nucleic acid molecule of claims 51 or 52, wherein said nucleic acid molecule comprises between 12 and 100 bases complementary to RNA encoding CDP. 58. The nucleic acid molecule of claims 51 or 52, wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to RNA encoding CDP. 10 59. The nucleic acid molecule of claim 55, wherein said nucleic acid molecule comprises any of sequence of Seq ID Nos 6389-6928. 60. The nucleic acid molecule of claim 51, wherein said nucleic acid molecule is an enzymatic DNA molecule. 61. A cell including a nucleic acid molecule of any of claims 1, 14, 25, 32, 39, or 50. 15 62. The cell of claim 61, wherein said cell is a mammalian cell. 63. An expression vector comprising nucleic acid sequence encoding the nucleic acid molecule of any of claims 1, 14, 25, 32, 39, or 50, in a manner which allows expression and/or delivery of that nucleic acid molecule. 64. A method for synthesis of erythropoietin protein, comprising the steps of: (a) 20 contacting a cell with a nucleic acid molecule of any of claims 1, 14, 25 or 32 under conditions suitable for the synthesis of said erythropoietin protein; and (b) purification of the erythropoietin protein from said cell. 65. A method for synthesis of granulocyte colony-stimulating factor (G-CSF) protein, comprising the steps of: (a) contacting a cell with a nucleic acid molecule of claim 25 39 under conditions suitable for the synthesis of said G-CSF protein; and (b) purification of the G-CSF protein from said cell. 66. A method for synthesis of interferon alpha protein, comprising the steps of: (a) contacting a cell with a nucleic acid molecule of claim 50 under conditions suitable for the synthesis of said interferon alpha protein; and (b) purification of 30 the interferon alpha protein from said cell. 67. A method of increasing the level of erythropoietin protein in a cell, comprising the step of contacting the cell with a nucleic acid molecule of any of claims 1, 14, 25 WO 00/61729 152 PCT/USOO/09721 or 32 under conditions suitable for achieving said increase in the level of said erythropoietin protein. 68. A method of increasing the level of G-CSF protein in a cell, comprising the step of contacting a cell with a nucleic acid molecule of claim 39 under conditions 5 suitable for achieving said increase in the level of said G-CSF protein. 69. A method of increasing the level of interferon alpha protein in a cell, comprising the step of contacting a cell with a nucleic acid molecule of claim 50 under conditions suitable for achieving said increase in the level of said interferon alpha protein. 10