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.

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.

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 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.

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:

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.

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 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/COUP-TF-1 (Miyajima et al., 1988, Nucleic Acids 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).

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 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 shown to negatively regulate a number of genes including gamma-globin, NCAM, and gp91-phox gene, neutrophil collagenase, neutrophil gelatinase, and granulocyte colony stimulating factor (G-CSF) (Khanna-Gupta et al., 1997, Blood 90,2784-

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 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.

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 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.

Summarv 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- 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.

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

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 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 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 261,1004).

By"2-SA 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.

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. Acad. Sci. USA 89,504).

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 complementarity in a substrate binding region to a specified gene target, and also has

an enzymatic activity that specifically cleaves RNA or DNA in that target. That is, the nucleic acid molecule with endonuclease activity is able to intramolecularly or intermolecularly cleave RNA or DNA and thereby inactivate a target RNA or DNA molecule. This complementarity functions to allow sufficient hybridization of the enzymatic RNA molecule to the target RNA or DNA to allow the cleavage to occur.

100% complementarity is preferred, but complementarity as low as 50-75% may also be useful in this invention. The nucleic acids may be modified at the base, sugar, and/or phosphate groups. The term enzymatic nucleic acid is used interchangeably with phrases such as ribozymes, catalytic RNA, enzymatic RNA, catalytic DNA, catalytic oligonucleotides, nucleozyme, DNAzyme, RNA enzyme, 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 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).

By"enzymatic portion"or"catalytic domain"is meant that portion/region of the ribozyme essential for cleavage of a nucleic acid substrate (for example see Figure 1).

By"substrate binding arm"or"substrate binding domain"is meant that portion/region of a ribozyme which is complementary to (i. e., able to base-pair with) a portion of its substrate. Generally, such complementarity is 100%, but can be less if desired. For example, as few as 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 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

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 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 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 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, 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.

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 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

skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule (Cech et al., U. S. Patent No. 4,987,071).

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- 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 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.

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, 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 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

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 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 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 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 inhibit the expression of genes capable of repressing interferon-alpha (IFN-a).

Repressors of IFN-a 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 acids, 2-SA 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- 2795) and Genesis (Xu et al, 1998, Leukemia, 12,207-2012).

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 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 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 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/COUP-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 Tables.

In yet another embodiment, the invention features antisense nucleic acid molecules and 2-SA 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 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 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

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 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 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 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 ) 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 ("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 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

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.

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 based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the ribozymes are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of ribozymes. Such vectors might be repeatedly administered as necessary. Once expressed, the ribozymes cleave the target RNA. Delivery of ribozyme expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that would allow for introduction into the desired target cell (for a review see Couture and Stinchcomb, 1996, TIG., 12,510). In another aspect of the invention, ribozymes that cleave target molecules and inhibit cell proliferation are expressed from transcription units inserted into DNA, RNA, or viral vectors.

Preferably, the recombinant vectors capable of expressing the ribozymes are locally delivered as described above, and transiently persist in smooth muscle cells.

However, other mammalian cell vectors that direct the expression of RNA may be used for this purpose.

By"patient"is meant an organism which is a donor or recipient of explanted cells or the cells themselves."Patient"also refers to an organism to which enzymatic nucleic acid molecules can be administered. Preferably, a patient is a mammal or mammalian cells. More preferably, a patient is a human or human cells.

By"vectors"is meant any nucleic acid-and/or viral-based technique used to deliver a desired nucleic acid.

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 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 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 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 following description of the preferred embodiments thereof, and from the claims.

Description Of The Preferred Embodiments The drawings will first briefly be described.

Figure 1 shows the secondary structure model for seven different classes of enzymatic nucleic acid molecules. Arrow indicates the site of cleavage.---------indicate the target sequence. Lines interspersed with dots are meant to indicate tertiary interactions.-is meant to indicate base-paired interaction. Group I Intron: P1-P9.0 represent various stem-loop structures (Cech et al., 1994, Nature Struc. Bio., 1,273).

RNase P (M1RNA): EGS represents external guide sequence (Forster et al., 1990, Science, 249,783; Pace et al., 1990, J. Biol. Chem., 265,3587). Group II Intron: 5'SS

means 5'splice site; 3'SS means 3'-splice site; IBS means intron 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 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 1-111 can be of any length and may be symmetrical or asymmetrical (Usman et al., 1996, Curr. Op. Struct. Bio., 1,527). Hairpin Ribozyme: Helix 1,4 and 5 can be of any length; Helix 2 is between 3 and 8 base-pairs long; Y is a pyrimidine; Helix 2 (H2) is provided with a least 4 base pairs (i. e., n is 1,2,3 or 4) and helix 5 can be optionally provided of length 2 or 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 2 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 instance, each N and N'independently is any normal or modified base and each dash represents a potential base-pairing interaction. These nucleotides may be modified at the sugar, base or phosphate. Complete base-pairing is not required in the helices, but is preferred. Helix 1 and 4 can be of any size (i. e., o and p is each independently from 0 to any number, e. g., 20) as long as some base-pairing is maintained. Essential bases are shown as specific bases in the structure, but those in the art will recognize that one or more may be modified chemically (abasic, base, sugar and/or phosphate modifications) or replaced with another base without significant effect. Helix 4 can be formed from two separate molecules, i. e., without a connecting loop. The connecting loop when present may be a ribonucleotide with or without modifications to its base, sugar or phosphate.

"q"> is 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 targeting hGATA-2 which has the sequence contained in Seq. I. D. No. 281.

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 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.

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 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 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-TRl RNA.

Figure 8 is a bar graph demonstrating increased Epo expression compared to 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-TRl RNA.

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 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 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 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 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 (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 production of these red blood cells (Maxwell & Radcliffe, supra). By inhibiting the

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 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 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 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 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 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.

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

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 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 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 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 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 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 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

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 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 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 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 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 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 enzymatic RNAs are known presently. In addition, several in vitro selection (evolution) strategies (Orgel, 1979, Proc. R. Soc. London, B 205,435) have been

used to evolve new nucleic acid catalysts capable of catalyzing cleavage and ligation of phosphodiester linkages (Joyce, 1989, Gene, 82,83-87; Beaudry et al., 1992, Science 257,635-641; Joyce, 1992, Scientific American 267,90-97; Breaker et al., 1994, TIBTECH 12,268; Bartel et al., 1993, Science 261: 1411-1418; Szostak, 1993, TIBS 17,89-93; Kumar et al., 1995, FASEB J., 9,1183; Breaker, 1996, Curr. Op.

Biotech., 7,442; Santoro et al., 1997, Proc. Natl. Acad. Sci., 94,4262; Tang et al., 1997, RNA 3,914; Nakamaye & Eckstein, 1994, supra; Long & Uhlenbeck, 1994, supra; Ishizaka et al., 1995, supra; Vaish et al., 1997, Biochemistry 36,6495; all of these are incorporated by reference herein). Each can catalyze a series of reactions including the hydrolysis of phosphodiester bonds in 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 enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets.

The enzymatic nature of a ribozyme 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 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 ribozyme.

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, 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 as therapeutic agents for human disease (Usman & McSwiggen, 1995 Ann. Rep.

Med. Chem. 30,285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38,2023- 2037). Ribozymes can be designed to cleave specific RNA targets within the background of cellular RNA. Such a cleavage event renders the RNA non- functional and abrogates protein expression from that RNA. In this manner, synthesis of a protein associated with a disease state can be selectively inhibited.

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 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 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 enzymatic nucleic acid molecules follows the procedure as described in Usman et

al., 1987 J. Am. Chem. Soc., 109,7845; Scaringe et al., 1990 Nucleic Acids Res., 18,5433; and Wincott et al., 1995 Nucleic Acids Res. 23,2677-2684 and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. In a non-limiting example, small scale 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 umol scale can be done on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, CA) with minimal modification to the cycle. A 15-fold excess (31 pL of 0. 1 M = 3.1 umol) of phosphoramidite and a 38.7-fold excess of S-ethyl tetrazole (31 cl 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, 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 mM pyridine, 9% water in THF (PERSEPTIVETM). 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 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 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

of a solution of 1.5 mL N-methylpyrrolidinone, 750 uL 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 NH4HCO3.

Alternatively, for the one-pot protocol, the polymer-bound trityl-on 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 NH4HC03- For purification of the trityl-on oligomers, the quenched NH4HCO3 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 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 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 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

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 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 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 (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.

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 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.

The present invention also includes pharmaceutically acceptable formulations of the compounds described. These formulations include salts of the above

compounds, e. g., acid addition salts, for example, salts of hydrochloric, hydrobromic, acetic acid, and benzene sulfonic acid.

A pharmacological composition or formulation refers to a composition or formulation in a form suitable for administration, e. g., systemic administration, into a cell or patient, preferably a human. Suitable forms, in part, depend upon the use or the route of entry, for example oral, transdermal, or by injection. Such forms should not prevent the composition or formulation to reach a target cell (i. e., a cell to which the negatively charged polymer is desired to be delivered to). For example, pharmacological compositions injecte into the blood stream should be soluble.

Other factors are known in the art, and include considerations such as toxicity and forms which prevent the composition or formulation from exerting its effect.

By"systemic administration"is meant in vivo systemic absorption or accumulation of drugs in the blood stream followed by distribution throughout the entire body. Administration routes which lead to systemic absorption include, without limitations: intravenous, subcutaneous, intraperitoneal, inhalation, oral, intrapulmonary and intramuscular. Each of these administration routes expose the desired negatively charged polymers, e. g., nucleic acids, to an accessible diseased tissue. The rate of entry of a drug into the circulation has been shown to be a function of molecular weight or size. The use of a liposome or other drug carrier comprising the compounds of the instant invention can potentially localize the drug, for example, in certain tissue types, such as the tissues of the reticular endothelial system (RES). A liposome formulation which can facilitate the association of drug with the surface of cells, such as, lymphocytes and macrophages is also useful. This approach may provide enhanced delivery of the drug to target cells by taking advantage of the 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 increasing the accumulation of drugs in target tissues. This class of drug carriers resists opsonization and elimination by the mononuclear phagocytic system (MPS or

RES), thereby enabling longer blood circulation times and enhanced tissue exposure for the encapsulated drug (Lasic et 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 neovascularized target tissues (Lasic et al., Science 1995,267,1275-1276; Oku et al., 1995, Biochim. Biophys. Acta, 86-90). 86-90). long-circulating long-circulating liposomes enhance the pharmacokinetics and pharmacodynamics of DNA and RNA, particularly compared to conventional cationic liposomes which are known to accumulate in tissues of the MPS (Liu et al., J. Biol. Chem. 1995,42,24864-24870; Choi et al., International PCT Publication No. WO 96/10391; Ansell et al., International PCT Publication No. WO 96/10390; Holland et al., International PCT Publication No. WO 96/10392; all of these are incorporated by reference herein).

Long-circulating liposomes are also likely to protect drugs from nuclease degradation to a greater extent compared to cationic liposomes, based on their ability to avoid accumulation in metabolically aggressive MPS tissues such as the liver and spleen. All of these references are incorporated by reference herein.

The present invention also includes compositions prepared for storage or administration which include a pharmaceutically effective amount of the desired compounds in a pharmaceutically acceptable carrier or diluent. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985) hereby incorporated by reference herein. For example, preservatives, stabilizers, dyes and flavoring agents may be provided. Id. at 1449. These include sodium benzoate, sorbic acid and esters ofp-hydroxybenzoic acid. In addition, antioxidants and suspending agents may be used. Id.

A pharmaceutically effective dose is that dose required to prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) of a disease state. The pharmaceutically effective dose depends on the type of disease, the composition used, the route of administration, the type of mammal being treated, the physical characteristics of the specific mammal under consideration, concurrent medication, and other factors which those skilled in the

medical arts will recognize. Generally, an amount between 0.1 mg/kg and 100 mg/kg body weight/day of active ingredients is administered dependent upon potency of the negatively charged polymer.

The nucleic acid molecules of the present invention may also be administered 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 promoters (e. g., Izant and Weintraub, 1985 Science 229,345; McGarry and Lindquist, 1986 Proc. Natl. Acad. Sci. USA 83,399; Scanlon et al., 1991, Proc.

Natl. Acad. Sci. USA, 88,10591-5; Kashani-Sabet et al., 1992 Antisense Res. Dev., 2,3-15; Dropulic et al., 1992 J. Virol, 66,1432-41; Weerasinghe et al., 1991 J.

Virol, 65,5531-4; Ojwang et al., 1992 Proc. Natl. Acad. Sci. USA 89,10802-6; Chen et al., 1992 Nucleic Acids Res., 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 of such nucleic acids can be augmented by their release from the primary transcript by a ribozyme (Draper et al., PCT WO 93/23569, and Sullivan et al., PCT WO 94/02595; Ohkawa et al., 1992 Nucleic Acids Symp. Ser., 27,15-6; Taira et al., 1991, Nucleic Acids Res., 19,5125-30; Ventura et al., 1993 Nucleic Acids Res., 21, 3249-55; Chowrira et al., 1994 J. Biol. Chem. 269,25856; all of the references are hereby incorporated in their totality by reference herein).

In another aspect of the invention, enzymatic nucleic acid molecules that cleave target molecules are expressed from transcription units (see for example Couture et al., 1996, TIG., 12,510) inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme expressing viral vectors could be constructed based on, but not limited to, adeno- associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant

vectors capable of expressing the ribozymes are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of ribozymes. Such vectors might be repeatedly administered as necessary. Once expressed, the ribozymes cleave the target RNA. The active ribozyme contains an enzymatic center or core equivalent to those in the examples, and binding arms able to bind target nucleic acid molecules such that cleavage at the target site occurs. Other sequences may be present which do not interfere with such cleavage. Delivery of ribozyme expressing vectors could be systemic, such as by 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 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, 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 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 (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 1), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol III promoters will be expressed at high levels in all cells; the levels of a given pol 11 promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers,

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 Methods Enzymol., 217,47-66; Zhou et al., 1990 Mol. Cell. Biol., 10,4529-37).

Several investigators have demonstrated that ribozymes expressed from such promoters can function in mammalian cells (e. g. Kashani-Sabet et al., 1992 Antisense Res. Dev., 2,3-15; Ojwang et al., 1992 Proc. Natl. Acad. Sci. U S A, 89, 10802-6; Chen et al., 1992 Nucleic Acids Res., 20,4581-9; Yu et al., 1993 Proc.

Natl. Acad. Sci. U S A, 90,6340-4; L'Huillier et al., 1992 EMBO J. 11,4411-8; Lisziewicz et al., 1993 Proc. Natl. Acad. Sci. U. S. A., 90,8000-4; Thompson et al., 1995 Nucleic Acids Res. 23,2259; Sullenger & Cech, 1993, Science, 262,1566).

More specifically, transcription units such as the ones derived from genes encoding U6 small nuclear (snRNA), transfer RNA (tRNA) and adenovirus VA RNA are useful in generating high concentrations of desired RNA molecules such as ribozymes in cells (Thompson et al., supra; Couture and Stinchcomb, 1996, supra; Noonberg et al., 1994, Nucleic Acid Res., 22,2830; Noonberg et al., US Patent No.

5,624,803; Good et al., 1997, Gene Ther. 4,45; Beigelman et al., International PCT Publication No. WO 96/18736; all of these publications are incorporated by reference herein. The above 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).

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 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

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 frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In yet another embodiment the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) a gene encoding at least one said nucleic acid molecule; and wherein said gene is operably linked to said initiation region, said intron and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In another embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) an open reading frame; e) a gene encoding at least one said nucleic acid molecule, wherein said gene is operably linked to the 3'-end of said open reading frame; and wherein said gene is operably linked to said initiation region, said intron, said open reading frame and said termination region, in a manner which allows 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 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, 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 Ribozvme Activity Catalytic activity of the ribozymes described in the instant invention can be optimized as described by Draper et al., supra. The details will not be repeated here,

but include altering the length of the ribozyme binding arms, or chemically synthesizing ribozymes with modifications (base, sugar and/or phosphate) that prevent their degradation by serum ribonucleases and/or enhance their enzymatic activity (see e. g., Eckstein et al., International Publication No. W092/07065; Perrault et al., 1990 Nature 344,565; Pieken et al., 1991 Science 253,314; Usman and Cedergren, 1992 Trends in Biochem. Sci. 17,334; Usman et al., International Publication No. WO 93/15187; and Rossi et al., International Publication No.

WO 91/03162; Sproat, US Patent No. 5,334,711; and Burgin et al., supra; all of these describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties of enzymatic RNA molecules). Modifications which enhance their efficacy in cells, and removal of bases from stem loop structures to shorten RNA synthesis times and reduce chemical requirements are desired. (All these publications are hereby incorporated by reference herein).

There are several examples in the art describing sugar, base and phosphate modifications that can be 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 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 Pieken et al. Science 1991,253,314- 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 incorporation of sugar, base and/or phosphate modifications and the like into ribozymes without inhibiting catalysis, and are incorporated by reference herein. In

view of such teachings, similar modifications can be used as described herein to modify the nucleic acid catalysts of the instant invention.

Nucleic acid catalysts having chemical modifications which maintain or enhance enzymatic activity are provided. Such nucleic acid is also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. As exemplified herein such ribozymes are useful in a cell and/or in vivo even if activity over all is reduced 10 fold (Burgin et al., 1996, Biochemistry, 35,14090). Such ribozymes herein are said to"maintain" the enzymatic activity on all RNA ribozyme.

Therapeutic ribozymes delivered exogenously must optimally be stable within cells until translation of the target RNA has been inhibited long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, ribozymes must be resistant to nucleases in order to function as effective intracellular therapeutic agents.

Improvements in the chemical synthesis of RNA (Wincott et al., 1995 Nucleic Acids Res. 23,2677; incorporated by reference herein) have expanded the ability to modify ribozymes by introducing nucleotide modifications to enhance their nuclease stability as described above.

By"enhanced enzymatic activity"is meant to include activity measured in 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 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 ribozymes herein are said to"maintain"the enzymatic activity on all RNA ribozyme.

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 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.

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 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 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 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 chemotherapy in C57B1/6 mice which is an indication of enhanced Epo production.

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 uL volume (Day- 0).

For all blood sample collection, animals are euthanized by C02 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 CDDP-treated animals are obtained beginning on Day-1 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 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.

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 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) subcutaneously or intravenously, subcutaneous bolus, direct i. p. injection or intravenously via the tail vein.

(2) Chronic Renal Failure-Induced Anemia in C57/B16 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 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 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 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.

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/ 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 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

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 C02 asphyxiation. Blood samples, body weights and spleen weights are obtained from 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 (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 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 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.

(3) Chemotherapy-Induced Myelosuppression in C57B16 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 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.

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 jj. L 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.

For all blood sample collections, animals are euthanized by C02 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 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 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 g/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.

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 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

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 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 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 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.

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 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 score. The clinical scoring system is as follows: 0.0 = Normal

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 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 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 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 (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., 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. injection or intravenously via the tail vein.

(6) B16 melanoma in C57/Bl6 Mice (Nishimura et al., 1985, Clin Exp Metastasis 3,295-304): 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. Two syngeneic melanoma cell lines, B16/B16 and B16/F10, are utilized.

Experimental Procedure : All studies are performed on pathogen-free, 25- 30g female C57/BI6 mice. Mice are housed in a pathogen-free environment and allowed food and water ad lib.

B16/B16: On Day 0, animals are injecte with B16/B16 cells (5x105), SC in 100 pl normal saline, mid-dorsal, in the scapular region. Primary tumor volume are 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 = 0.5abc where a=longest axis of the tumor 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 mm3, the primary tumors are removed. 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 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.

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 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

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°C 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 intravenously via the tail vein.

B16/F10: On Day 0, animals are injecte with B16/F10 (5x104) 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 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.

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 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°C 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 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, 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

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 water ad lib. On Day 0, animals are injecte with COLON-26 cells (1 x 106) 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).

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.

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 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-70°C 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 intravenously via the tail vein.

Examples The following are non-limiting examples showing the selection, isolation, synthesis and activity of enzymatic nucleic acids of the instant invention.

The following examples demonstrate the selection of ribozymes that cleave TR2 Orphan Receptor, EAR3/COUP-TF-1, GATA transcription factors, IRF-2,

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 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- 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 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 sites on the basis of folding. Hammerhead ribozymes were designed that could bind each target (see Figure 1) and were individually analyzed by computer folding (Christoffersen et al., 1994 J. Mol. Struc. Theochem, 311,273; Jaeger et al., 1989, Proc. Natl. Acad. Sci. USA, 86,7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA. An example of a ribozyme targeted to hGATA-2 is shown in figure 2.

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 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 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 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 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 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 nucleotide location within the hGATA-2 mRNA are given in Table III.

Cleavage Reactions : Full-length or partially full-length, internally-labeled target RNA for ribozyme cleavage assay is prepared by in vitro transcription in the presence of [a-32p] CTP, passed over a G 50 Sephadex column by spin chromatography and used as substrate RNA without further purification.

Alternately, substrates are 5'-32P-end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2X concentration of purified ribozyme in ribozyme cleavage buffer (50 mM Tris-HCl, pH 7.5 at 37°C, 10 mM MgCl2) and the cleavage reaction was initiated by adding the 2X ribozyme mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in 0 cleavage buffer. As an initial screen, assays are carried out for 1 hour at 37 C using a final concentration of either 40 nM or 1 mM ribozyme, i. e., ribozyme excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% xylene cyanol after which the sample is 0 heated to 95 C for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph of the gel. The percentage of cleavage is determined by PHOSPHOR IMAGER quantitation of bands representing the intact substrate and the cleavage products.

Example 5: Increased Expression of Erythropoietin by Inhibition of Repressors of Ervthropoietin 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 production. The ability of these ribozymes to increase Epo expression in both induced (with CoCl2) and non-induced cells was also tested. Erythropoietin (Epo) is produced in the adult kidney and fetal liver in response to hypoxia and CoCl2. Two human hepatoma cell lines, Hep G2 and Hep 3B, exhibit regulated expression of Epo in response to hypoxia and CoCl2. Ribozymes were tested under non-induced and induced conditions to determine if Epo levels could be increased under one or both conditions.

Hep3B cells were plated at 1.8 x 104 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 ug/ml of cationic lipid. The sequences for the ribozymes and the irrelevant controls (IR1 & IR2) are given in table VIII. Cells were then induced to express Erythropoietin by applying cell culture media containing CoCl2 (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 assay using the manufacturer's protocol. The ELISA for quantification of erythropoietin was performed using QUANTIKINE IVDTM 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 induction respectively.

Example 6: Elevated Expression of Erythropoietin Over Time Using Ribozvmes Targeting Epo Repressors Hep3B cells were prepared as described in example 5. Ribozymes (RPI No. 14260 (targeting hGATA-2) & 144521 (targeting EAR3/COUP-TR1; table VIII) at a concentration of 100nm were transfected into Hep3B cells using 5 pg/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).

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-TRl will result in elevated expression of Epo in Hep3B cells compared to irrelevant and untreated controls.

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 activity and the structure of the target RNA allows the detection of mutations in any region of the molecule which alters the base-pairing and three-dimensional structure of the target RNA. By using multiple ribozymes described in this invention, one may map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with ribozymes may be used to inhibit gene expression and define the role (essentially) of specified gene products in the progression of disease. In this manner, other genetic targets may be defined as important mediators of the disease. 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 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 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 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 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

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 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., 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.

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 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 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 regulation of genes has been demonstrated in plants (Preston et al., 1998, J.

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, 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 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, 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.

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 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 intention that in the use of such terms and expressions of excluding any equivalents

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 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 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 TABLEI Characteristics of naturally occurring ribozymes Group I Introns Size : 0 to >1000 nucleotides.

# Requires a U in the target sequence immediately 5'of the cleavage site.

# Binds 4-6 nucleotides at the 5'-side of the cleavage site.

# Reaction mechanism: attack by the 3'-OH of guanosine to generate cleavage products with 3'-OH and 5'-guanosine.

# Additional protein cofactors required in some cases to help folding and maintainance of the active structure.

# Over 300 known members of this class. Found as an intervening sequence in Tetrahymena thermophila rRNA, fungal mitochondria, chloroplasts, phage T4, blue-green algae, and others.

# Major structural features largely established through phylogenetic comparisons, mutagenesis, and biochemical studies [].

# Complete kinetic framework established for one ribozyme r, v, v, v']. ofribozymefoldingandsubstratedockingunderway[vii,viii,ix].#S tudies <BR> <BR> <BR> <BR> modificationinvestigationofimportantresiduesweilestablished[ x,xi].#Chemical # 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 Fgalactosidase sequences onto the defective message [""].

RNAse P RNA (M1 RNA) Size : ~290 to 400 nucleotides. <BR> <BR> <BR> portionofaubiquitousribonucleoproteinenzyme.#RNA <BR> <BR> <BR> tRNAprecursorstoformmaturetRNA[xiii].#Cleaves mechanism:possibleattack#Reaction by generatecleavageproductswith3'-to OH and 5'-phosphate.

# RNAse P is found throughout the prokaryotes and eukaryotes. The RNA subunit has been sequenced from bacteria, yeast, rodents, and primates. ofendogenousRNAsePfortherapeuticapplicationsispossiblethroug h#Recruitment hybridization of an External Guide Sequence (EGS) to the target RNA [xiv,xv] ##Important phosphate and 2'OH contacts recently identified [xvi,xvii] Group Introns # Size : >1000 nucleotides.

Trans cleavage of target RNAs recently demonstrated [xviii,xix].

Table I * 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 ('°"°"] in addition to RNA cleavage and ligation.

# Major structural features largely established through phylogenetic comparisons[xxii].

Ohcontactsbeginningtobeidentified[xxiii]#Important2' ##Kinetic framework under development [xxiv] Neurospora VS RNA Size :-144 nucleotides.

Trans cleavage of hairpin target RNAs recently demonstrated[xxv].

# Sequence requirements not fully determined.

# Reaction mechanism: attack by 2'-OH 5'to the scissile bond to generate cleavage products with 2', 3'-cyclic phosphate and 5'-OH ends.

Binding sites and structural requirements not fully determined.

Only 1 known member of this class. Found in Neurospora VS RNA.

Hammerhead Ribozyme (see text for references) Size : ~13 to 40 nucleotides.

Requires the target sequence UH immediately 5'of the cleavage site.

# Binds a variable number nucleotides on both sides of the cleavage site.

Reaction mechanism : attack by 2'-OH 5'to the scissile bond to generate cleavage products with 2', 3'-cyclic phosphate and 5'-OH ends.

14 known members of this class. Found in a number of plant pathogens (virusoids) that use RNA as the infectious agent. structuralfeatureslargelydefined,including2crystalstructures [xxvi,xxvii]#Essential # Minimal ligation activity demonstrated (for engineering through invitro selection) [xxviii] kineticframeworkestablishedfortwoormoreribozymes[xxix].#Comp lete <BR> <BR> <BR> <BR> Chemical modification investigation of important residues well established [Xxx].

Hairpin Ribozyme * Size:-50 nucleotides.

Requires the target sequence GUC immediately 3'of the cleavage site.

Binds 4-6 nucleotides at the 5'-side of the cleavage site and a variable number to the 3'- side of the cleavage site.

'Reaction mechanism : attack by 2'-OH 5'to the scissile bond to generate cleavage products with 2', 3'-cyclic phosphate and 5'-OH ends.

3 known members of this class. Found in three plant pathogen (satellite RNAs of the tobacco ringspot virus, arabis mosaic virus and chicory yellow mottle virus) which uses RNA as the infectious agent.

##Essential structural features largely defined [xxxi,xxxii,xxxiii,xxxiv] # Ligation activity (in addition to cleavage activity) makes ribozyme amenable to engineering through in vitro selection [Xxxv] 'Complete kinetic framework established for one ribozyme [Xxxvi] Chemical modification investigation of important residues begun [xxxvii,xxxviii].

Hepatitis Delta Virus (HDV) Ribozyme # Size:-60 nucleotides.

Trans cleavage of target RNAs demonstrated [Xxxix].

# Binding sites and structural requirements not fully determined, although no sequences 5'of cleavage site are required. Folded ribozyme contains a pseudoknot structure [xi].

# 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 [xli '. Michel, Francois; Westhof, Eric. Slippery substrates. Nat. Struct. Biol. (1994), 1 (1), 5-7. ii. Lisacek, Frederique ; Diaz, Yolande; Michel, Francois. Automatic identification of group I intron cores in genomic DNA sequences. J. Mot. 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.

'". 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. vi. Bevilacqua, Philip C.; Sugimoto, Naoki; Turner, Douglas H.. A mechanistic framework for the second step of splicing catalyzed by the Tetrahymena ribozyme. Biochemistry (1996), 35 (2), 648-58.

Li, 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. vEu. Baneree, Aloke Raj; Tumer, Douglas H.. The time dependence of chemical modification reveals slow steps in the folding of a group I ribozyme. Biochemistry (1995), 34 (19), 6504-12.

'". Zarrinkar, Patrick P.; Williamson, James R. The P9.1-P9.2 peripheral extension helps guide folding of the Tetrahymena ribozyme. Nucleic Acids Res. (1996), 24 (5), 854-8.

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.

ScottA.;Cech,ThomasR.,ExocyclicAmineoftheConservedG.cntdot.U Pairatthexi.Strobel, Cleavage Site of the Tetrahymena Ribozyme Contributes to 5'-Splic site Selection 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. xiii, Robertson, H. D.; Altman, S.; Smith, J. D. J. Biol. Chem., Z4z 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 ribozyme RNase P RNA. RNA (1995), 1 (2), 210-18.

"". Pan, Tao; Loria, Andrew; Zhong, Kun. Probing of tertiary interactions in RNA: 2'-hydroxyl- base contacts between the RNase P RNA and pre-tRNA. Proc. Natl. Acad. Sci. U. S. A. (1995), 92 (26), 12510-14.

""". Pyle, Anna Marie; Green, Justin B.. Building a Kinetic Framework for Group II Intron Ribozyme Activity: Quantitation of Interdomain Binding and Reaction Rate. Biochemistry (1994), 33 (9), 2716-25. vx. Michels, William J. Jr.; Pyle, Anna Marie. Conversion of a Group II Intron into a New Multiple- Turnover Ribozyme that Selectively Cleaves Oligonucleotides: Elucidation of Reaction Mechanism and Structure/Function Relationships. Biochemistry (1995), 34 (9), 2965-77.

". Zimmerly, Steven; Guo, Huatao; Eskes, Robert; Yang, Jian ; Perlman, Philip S.; Lambowitz, Alan M.. A group II intron RNA is a catalytic component of a DNA endonuclease involved in intron mobility. Cell (Cambridge, Mass.) (1995), 83 (4), 529-38.

Griffin, Edmund A., Jr.; Qin, Zhifeng; Michels, Williams J., Jr.; Pyle, Anna Marie. Group II intron ribozymes that cleave DNA and RNA linkages with similar efficiency, and lack contacts with substrate 2'-hydroxyl groups. Chem. Biol. (1995), 2 (11), 761-70. uii. Michel, Francois; Ferat, Jean Luc. Structure and activities of group II introns. Annu. Rev.

Biochem. (1995), 64,435-61. xxii. 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. xxiv. 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. xxv. 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. xxviii, Long, D., Uhlenbeck, O., Hertel, K Ligation with hammerhead ribozymes. US Patent No.

5,633,133.

Hertel, K. J., Herschlag, D., Uhlenbeck, O. 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. xxxi 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. xxxiii . 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 (1995), 34 (12), 4068-76.

Schmidt, Sabine; Beigelman, Leonid; Karpeiskv, 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. i. 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. ii. Puttaraju, M.; Perrotta, Anne T.; Been, Michael D.. A circular trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res. (1993), 21 (18), 4253-8.

Table II: 0.2 gmol RNA Synthesis Cycle Reagents Equivalents Amounts (L) 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 24415Iodine20.6 * Wait time does not include contact time during delivery.

Table III. Hammerhead ribozymes targeting GATA Transcription factors (1,2,3,4, and 6) and the complementary Sequences Seq.RZSeq.SubstratePosTarget I.D. I.D. No 1CUCAGUGUCUGAUGAGXCGAAAUCCCAGG1697CCTGGGATCACACTGAG37HSERYF1 2GAUGUGGCCUGAUGAGXCGAAAGCUCAGU1698ACTGAGCTTGCCACATC48HSERYF1 3GCCUUGGGCUGAUGAGXCGAAAUGUGGCA1699TGCCACATCCCCAAGGC56HSERYF1 4UGGUUGCGCUGAUGAGXCGAAAGGGUUCG1700CGAACCCTCCGCAACCA76HSERYF1 96 UGGGGAUUCUGAUGAGXCGAAACCUGGGC1701GCCCAGGTTAATCCCCA5 6CUGGGGAUCUGAUGAGXCGAAAACCUGGG1702CCCAGGTTAATCCCCAG97HSERYF1 100 CCUCUGGGCUGAUGAGXCGAAAUUAACCU1703AGGTTAATCCCCAGAGG7 8ACUCCAUGCUGAUGAGXCGAAAGCCUCUG1704CAGAGGCTCCATGGAGT111HSERYF 1 120 GGCCAGGGCUGAUGAGXCGAAACUCCAUG1705CATGGAGTTCCCTGGCC9 10AGGCCAGGCUGAUGAGXCGAAAACUCCAU1706ATGGAGTTCCCTGGCCT121HSERY F1 11UCCCCAGGCUGAUGAGXCGAAACCCCAGG1707CCTGGGGTCCCTGGGGA137HSERY F1 12GGGGCUCUCUGAUGAGXCGAAAGGUCCCC1708GGGGACCTCAGAGCCCC147HSERY F1 13AACUGGGGCUGAUGAGXCGAAAGGGGCUC1709GAGCCCCTCCCCCAGTT157HSERY F1 14GAUCCACACUGAUGAGXCGAAACUGGGGG1710CCCCCAGTTTGTGGATC165HSERY F1 15GGAUCCACCUGAUGAGXCGAAAACUGGGG1711CCCCAGTTTGTGGATOC166HSERY F1 16CAGAGCAGCUGAUGAGXCGAAAUCCACAA1712TTGTGGATCCTGCTCTG173HSERY F1 179 HSERYF1 17 GGACACCA CUGAUGAG X CGAA AGCAGGAU 1713 ATOCTGCT C TGGTGTCC 186 HSERYF1 18 GUGUGGAG CUGAUGAG X CGAA ACACCAGA 1714 TCTGGTGT C CTCCACAC 189 HSERYF1 19 CUGGUGUG CUGAUGAG X CGAA AGGACACC 1715 GGTGTCCT C CACACCAG 201 HSERYF1 20 AAACCCCU CUGAUGAG X CGAA AUUCUGGU 1716 ACCAGAAT C AGGGGTTT 208 HSERYF1 21 GGGAAGAA CUGAUGAG X CGAA ACCCCUGA 1717 TCAGGGGT T TTCTTCCC 209 HSERYF1 22 GGGGAAGA CUGAUGAG X CGAA AACCCCUG 1718 CAGGGGTT T TCTTCCCC 210210HSERYF1 23 AGGGGAAG CUGAUGAG X CGAA AAACCCCU 1719 AGGGGTTT T CTTCCCCT 211211HSERYF1 24 GAGGGGAA CUGAUGAG X CGAA AAAACCCC 1720 GGGGTTTT C TTCCCCTC 25CAGAGGGGCUGAUGAGXCGAAAGAAAACC1721GGTTTTCTTCCCCTCTG213HSERY F1 26CCAGAGGGCUGAUGAGXCGAAAAGAAAAC1722GTTTTCTTCCCCTCTGG214HSERY F1 219219HSERYF1 27 CAGGCCCA CUGAUGAG X CGAA AGGGGAAG 1723 CTTCCCCT C TGGGCCTG 234 HSERYF1 28 CUGCAUCC CUGAUGAG X CGAA AGCCCUCA 1724 TGAGGGCT T GGATGCAG 248 HSERYF1 29 AGUGGAGG CUGAUGAG X CGAA AGCUGCUG 1725 CAGCAGCT T CCTCCACT 249 HSERYF1 30 CAGUGGAG CUGAUGAG X CGAA AAGCUGCU 1726 AGCAGCTT C CTCCACTG 252 HSERYF1 31 GGGCAGUG CUGAUGAG X CGAA AGGAAGCU 1727 AGCTTCCT C CACTGCCC 297 HSERYF1 32 CCCUGUAG CUGAUGAG X CGAA AGGCCAGU 1728 ACTGGCCT A CTACAGGG 300 HSERYF1 33 CGUCCCUG CUGAUGAG X CGAA AGUAGGCC 1729 GGCCTACT A CAGGGACG 318 HSERYF1 34 AGUGUCUG CUGAUGAG X CGAA AGGCCUCA 1730 TGAGGCCT A CAGACACT 327 HSERYF1 35 AGACUGGG CUGAUGAG X CGAA AGUGUCUG 1731 CAGACACT C CCCAGTCT 334 HSERYF1 36 ACCUGAAA CUGAUGAG X CGAA ACUGGGGA 1732 TCCCCAGT C TTTCAGGT 336 HSERYF1 37 ACACCUGA CUGAUGAG X CGAA AGACUGGG 1733 CCCAGTCT T TCAGGTGT 337 HSERYF1 38 UACACCUG CUGAUGAG X CGAA AAGACUGG 1734 CCAGTCTT T CAGGTGTA 338 HSERYF1 39 GUACACCU CUGAUGAG X CGAA AAAGACUG 1735 CAGTCTTT C AGGTGTAC 345 HSERYF1 40 GCAAUGGG CUGAUGAG X CGAA ACACCUGA 1736 TCAGGTGT A CCCATTGC 351 HSERYF1 41 AGUUGAGC CUGAUGAG X CGAA AUGGGUAC 1737 GTACCCAT T GCTCAACT 355 HSERYF1 42 AUACAGUU CUGAUGAG X CGAA AGCAAUGG 1738 CCATTGCT C AACTGTAT Table III. Hammerhead ribozymes targeting GATA transcription factors 4, and 6) and the complementary sequences 43CCCCUCCACUGAUGAGXCGAAACAGUUGA1739TCAACTGTATGGAGGGG362HSERY F1 44CCCCCUGGCUGAUGAGXCGAAAUCCCCUC1740GAGGGGATCCCAGGGGG373HSERY F1 45CAUAUGGUCUGAUGAGXCGAAAGCCCCCU1741AGGGGGCTCACCATATG384HSERY F1 46AGCCGGCACUGAUGAGXCGAAAUGGUGAG1742CTCACCATATGCCGGCT390HSERY F1 47UCUUGCCGCUGAUGAGXCGAAAGGCCCAG1743CTGGGCCTACGGCAAGA405HSERY F1 48GCAGGGUACUGAUGAGXCGAAAGCCCCGU1744ACGGGGCTCTACCCTGC421HSERY F1 49AGGCAGGGCUGAUGAGXCGAAAGAGCCCC1745GGGGCTCTACCCTGCCT423HSERY F1 50ACACAGUUCUGAUGAGXCGAAAGGCAGGG1746CCCTGCCTCAACTGTGT432HSERY F1 51GCGGGUGGCUGAUGAGXCGAAACACACAG1747CTGTGTGTCCCACCCGC443HSERY F1 52GGGGAGGACUGAUGAGXCGAAAGUCCUCG1748CGAGGACTCTCCTCCCC459HSERY F1 53CUGGGGAGCUGAUGAGXCGAAAGAGUCCU1749AGGACTCTCCTCCCCAG461HSERY F1 54GGCCUGGGCUGAUGAGXCGAAAGGAGAGU1750ACTCTCCTCCCCAGGCC464HSERY F1 55UCCAUCCACUGAUGAGXCGAAAUCUUCCA1751TGGAAGATCTGGATGGA482HSERY F1 56UCUCCAGGCUGAUGAGXCGAAAGCUGGUG1752CACCAGCTTCCTGGAGA507HSERY F1 57GUCUCCAGCUGAUGAGXCGAAAAGCUGGU1753ACCAGCTTCCTGGAGAC508HSERY F1 58UGUCUUCACUGAUGAGXCGAAAGUCUCCA1754TGGAGACTTTGAAGACA518HSERY F1 519 CUGUCUUCCUGAUGAGXCGAAAAGUCUCC1755GGAGACTTTGAAGACAG59 60AGGGUCAGCUGAUGAGXCGAAAGGUCUGG1756CCAGACCTCCTGACCCT547HSERY F1 572 HSERYF1 61 GAGUGAUG CUGAUGAG X CGAA AGGCAGUG 1757 CACTGCCT T CATCACTC 62GGAGUGAUCUGAUGAGXCGAAAAGGCAGU1758ACTGCCTTCATCACTCC573HSERY F1 63CAGGGAGUCUGAUGAGXCGAAAUGAAGGC1759GCCTTCATCACTCCCTG576HSERY F1 580 HSERYF1 64 XCGAAAGUGAUGA1760TCATCACTCCCTGTCCCCUGAUGAG 65CUAUUGGGCUGAUGAGXCGAAACAGGGAG1761CTCCCTGTCCCCAATAG586HSERY F1 66AUAAGCACCUGAUGAGXCGAAAUUGGGGA1762TCCCCAATAGTGCTTAT593HSERY F1 67GCCCCCAUCUGAUGAGXCGAAAGCACUAU1763ATAGTGCTTATGGGGGC599HSERY F1 68GGCCCCCACUGAUGAGXCGAAAAGCACUA1764TAGTGCTTATGGGGGCC600HSERY F1 69UACUGGAACUGAUGAGXCGAAAGUCAGGG1765CCCTGACTTTTCCAGTA615HSERY F1 70HUACUGGACUGAUGAGXCGAAAAGUCAGG1766CCTGACTTTTCCAGTAC616HSERY F1 71GGUACUGGCUGAUGAGXCGAAAAAGUCAG1767CTGACTTTTCCAGTACC617HSERY F1 72AGGUACUGCUGAUGAGXCGAAAAAAGUCA1768TGACTTTTCCAGTACCT618HSERY F1 73AAAGAAGGCUGAUGAGXCGAAACUGGAAA1769TTTCCAGTACCTTCTTT623HSERY F1 74GAGAAAAGCUGAUGAGXCGAAAGGUACUG1770CAGTACCTTCTTTTCTC627HSERY F1 75GGAGAAAACUGAUGAGXCGAAAAGGUACU1771AGTACCTTCTTTTCTCC628HSERY F1 76UGGGAGAACUGAUGAGXCGAAAGAAGGUA1772TACCTTCTTTTCTCCCA630HSERY F1 77GUGGGAGACUGAUGAGXCGAAAAGAAGGU1773ACCTTCTTTTCTCCCAC631HSERY F1 78GGUGGGAGCUGAUGAGXCGAAAAAGAAGG1774CCTTCTTTTCTCCCACC632HSERY F1 79CGGUGGGACUGAUGAGXCGAAAAAAGAAG1775CTTCTTTTCTCCCACCG633HSERY F1 80CCCGGUGGCUGAUGAGXCGAAAGAAAAGA1776TCTTTTCTCCCACCGGG635HSERY F1 81GCUGAAUUCUGAUGAGXCGAAAGGGGGCU1777AGCCCCCTCAATTCAGC652HSERY F1 82GGCUGCUGCUGAUGAGXCGAAAUUGAGGG1778CCCTCAATTCAGCAGCC656HSERY F1 657AGGCUGCUCUGAUGAGXCGAAAAUUGAGG1779CCTCAATTCAGCAGCCT83 84GAGAGGAACUGAUGAGXCGAAAGGCUGCU1780AGCAGCCTATTCCTCTC666HSERY F1 668 GGGAGAGGCUGAUGAGXCGAAAUAGGCUG1781CAGCCTATTCCTCTCCC85 86UGGGAGAGCUGAUGAGXCGAAAAUAGGCU1872AGCCTATTCCTCTCCCA669HSERY F1 Table m. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 87GCUUGGGACUGAUGAGXCGAAAGGAAUAG1783CTATTCCTCTCCCAAGC672HSERY F1 674 AAGCUUGGCUGAUGAGXCGAAAGAGGAAU1784ATTCCTCTCCCAAGCTT88 89GUUCCACGCUGAUGAGXCGAAAGCUUGGG1785CCCAAGCTTCGTGGAAC682HSERY F1 90AGUUCCACCUGAUGAGXCGAAAAGCUUGG1786CCAAGCTTCGTGGAACT683HSERY F1 692 HSERYF1 91 CAGGGGGA CUGAUGAG X CGAA AGUUCCAC 1787 GTGGAACT C TCCCCCTG 694 GGCAGGGGCUGAUGAGXCGAAAGAGUUCC1788GGAACTCTCCCCCTGCC92 704 HSERYF1 93 XCGAAAGGCAGGG1789CCCTGCCTCCCTGTGAGCUGAUGAG 94CCACAGUGCUGAUGAGXCGAAAGUGGCUG1790CAGCCACTCCACTGTGG749HSERY F1 95UGCAUAGGCUGAUGAGXCGAAAGUGGCCU1791AGGCCACTACCTATGCA780HSERY F1 96GCGUUGCACUGAUGAGXCGAAAGGUAGUG1792CACTACCTATGCAACGC784HSERY F1 97UUGUGAUACUGAUGAGXCGAAAGGCCGCA1793TGCGGCCTCTATCACAA802HSERY F1 98UCUUGUGACUGAUGAGXCGAAAGAGGCCG1974CGGCCTCTATCACAAGA804HSERY F1 99CAUCUUGUCUGAUGAGXCGAAAUAGAGGC1795GCCTCTATCACAAGATG806HSERY F1 100GGCCGGAUCUGAUGAGXCGAAAGGGGCCU1796AGGCCCCTCATCCGGCC835HSER YF1 101UUGGGCCGCUGAUGAGXCGAAAUGAGGGG1797CCCCTCATCCGGCCCAA838HSER YF1 102UUACUGACCUGAUGAGXCGAAAUCAGGCG1798CGCCTGATTGTCAGTAA859HSER YF1 103CGUUUACUCUGAUGAGXCGAAACAAUCAG1799CTGATTGTCAGTAAACG862HSER YF1 866 UGCCCGUUCUGAUGAGXCGAAACUGACAA1800TTGTCAGTAAACGGGCA104 878 GCACUGAGCUGAUGAGXCGAAACCUGCCC1801GGGCAGGTACTCAGTGC105 106GGUGCACUCUGAUGAGXCGAAAGUACCUG1802CAGGTACTCAGTGCACC881HSER YF1 107GCACACGGCUGAUGAGXCGAAAUCCCCAC1803GTGGGGATCCCGTGTGC941HSER YF1 108UUGUAGUACUGAUGAGXCGAAAGGCCGCA1804TGCGGCCTCTACTACAA964HSER YF1 109GCUUGUAGCUGAUGAGXCGAAAGAGGCCG1805CGGCCTCTACTACAAGC966HSER YF1 110GUAGCUUGCUGAUGAGXCGAAAGUAGAGG1806CCTCTACTACAAGCTAC969HSER YF1 111ACCUGGUGCUGAUGAGXCGAAAGCUUGUA1807TACAAGCTACACCAGGT976HSER YF1 112AGUCUGAACUGAUGAGXCGAAACCAUCCU1808AGGATGGTATTCAGACT1016HSE RYF1 113CGAGUCUGCUGAUGAGXCGAAAUACCAUC1809GATGGTATTCAGACTCG1018HSE RYF1 114UCGAGUCUCUGAUGAGXCGAAAAUACCAU1810ATGGTATTCAGACTCGA1019HSE RYF1 115GCGGUUUCCUGAUGAGXCGAAAGUCUGAA1811TTCAGACTCGAAACCGC1025HSE RYF1 116CUUUUCCACUGAUGAGXCGAAAUGCCUUG1812CAAGGCATCTGGAAAAG1041HSE RYF1 117CCAGACUGCUGAUGAGXCGAAAGCCCCGU1813ACGGGGCTCCAGTCTGG1068HSE RYF1 118GCCUCCCACUGAUGAGXCGAAACUGGAGC1814GCTCCAGTCTGGGAGGC1073HSE RYF1 119CCACCAUACUGAUGAGXCGAAAGCCACCA1815TGGTGGCTTTATGGTGG1113HSE RYF1 120ACCACCAUCUGAUGAGXCGAAAAGCCACC1816GGTGGCTTTATGGTGGT1114HSE RYF1 121CACCACCACUGAUGAGXCGAAAAAGCCAC1817GTGGCTTTATGGTGGTG1115HSE RYF1 1139 AUUCCCGCCUGAUGAGXCGAAACCGCUGC1818GCAGCGGTAGCGGGAAT122 123CUCCCCACCUGAUGAGXCGAAAUUCCCGC1819GCGGGAATTGTGGGGAG1148HSE RYF1 11631163HSERYF1 124 XCGAAAGCCACCU1820AGGTGGCTTCAGGCCTGCUGAUGAG 125UCAGGCCUCUGAUGAGXCGAAAAGCCACC1821GGTGGCTTCAGGCCTGA1164HSE RYF1 126AUGGGCAGCUGAUGAGXCGAAACCUGGGG1822CCCCAGGTACTGCCCAT1190HSE RYF1 127UUGGUAGACUGAUGAGXCGAAAUGGGCAG1823CTGCCCATCTCTACCAA1199HSE RYF1 128CCUUGGUACUGAUGAGXCGAAAGNUGGGC1824GCCCATCTCTACCAAGG1201HSE RYF1 129GGCCUUGGCUGAUGAGXCGAAAGAGAUGG1825CCATCTCTACCAAGGCC1203HSE RYF1 130CAGGCCCUCUGAUGAGXCGAAACAGCACC1826GGTGCTGTCAGGGCCTG1230HSE RYF1 Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1240 AGGUGGCUCUGAUGAGXCGAAAGAGGCCC1827GGGCCTGTTAGCCACCT131 132GAGGUGGCCUGAUGAGXCGAAAACAGGCC1828GGCCTGTTAGCCACCTC1241HSE RYF1 133AAAGGCAUCUGAUGAGXCGAAAGGUGGCU1829AGCCACCTCATGCCTTT1249HSE RYF1 134UCCAGGGACUGAUGAGXCGAAAGGCAUGA1830TCATGCCTTTCCCTGGA1256HSE RYF1 1257 GUCCAGGGCUGAUGAGXCGAAAAGGCAUG1831CATGCCTTTCCCTGGAC135 136GGUCCAGGCUGAUGAGXCGAAAAAGGCAU1832ATGCCTTTCCCTGGACC1258HSE RYF1 137GAGCCCAGCUGAUGAGXCGAAAGGGGUCC1833GGACCCCTACTGGGCTC1270HSE RYF1 138CCGUGGGUCUGAUGAGXCGAAAGCCCAGU1834ACTGGGCTCACCCACGG1278HSE RYF1 139UGGGGAAGCUGAUGAGXCGAAAGCCCGUG1835CACGGGCTCCTTCCCCA1290HSE RYF1 140CUGUGGGGCUGAUGAGXCGAAAGGAGCCC1836GGGCTCCTTCCCCACAG1293HSE RYF1 141CCUGUGGGCUGAUGAGXCGAAAAGGAGCC1837GGCTCCTTCCCCACAGG1294HSE RYF1 142CACCACAGCUGAUGAGXCGAAAGUGCUGG1838CCAGCACTACTGTGGTG1328HSE RYF1 143GCUGAGCGCUGAUGAGXCGAAAGCCACCA1839TGGTGGCTCCGCTCAGC1340HSE RYF1 144CAUGAGCUCUGAUGAGXCGAAAGCGGAGC1840GCTCCGCTCAGCTCATG1345HSE RYF1 145GCCCUCAUCUGAUGAGXCGAAAGCUGAGC1841GCTCAGCTCATGAGGGC1350HSE RYF1 146CUCCUCUGCUGAUGAGXCGAAAGGCCAUG1842CATGGCCTCCAGAGGAG1373HSE RYF1 147AGGAGAAGCUGAUGAGXCGAAACACCACC1843GGTGGTGTCCTTCTCCT1391HSE RYF1 148AAGAGGAGCUGAUGAGXCGAAAGGACACC1844GGTGTCCTTCTCCTCTT1394HSE RYF1 149CAAGAGGACUGAUGAGXCGAAAAGGACAC1845GTGTCCTTCTCCTCTTG1395HSE RYF1 150UACAAGAGCUGAUGAGXCGAAAGAAGGAC1846GTCCTTCTCCTCTTGTA1397HSE RYF1 1400 GGCUACAACUGAUGAGXCGAAAGGAGAAG1847CTTCTOCTCTTGTAGCC151 152CUGGCUACCUGAUGAGXCGAAAGAGGAGA1848TCTCCTCTTGTAGCCAG1402HSE RYF1 153AUUCUGGCCUGAUGAGXCGAAACAAGAGG1849CCTCTTGTAGCCAGAAT1405HSE RYF1 154UUGUCCAGCUGAUGAGXCGAAAUUCUGGC1850GCCAGAATTCTGGACAA1414HSE RYF1 155GUUGUCCACUGAUGAGXCGAAAAUUCUGG1851CCAGAATTCTGGACAAC1415HSE RYF1 156GGCCCAGACUGAUGAGXCGAAACUUGGGU1852ACCCAAGTCTCTGGGCC1430HSE RYF1 157GGGGCCCACUGAUGAGXCGAAAGACUUGG1853CCAAGTCTCTGGGCCCC1432HSE RYF1 158GAAGGUUCCUGAUGAGXCGAAAGCCAGGG1854CCCTGGCTTGAACCTTC1456HSE RYF1 159AAGCUUUGCUGAUGAGXCGAAAGGUUCAA1855TTGAACCTTCAAAGCTT1463HSE RYF1 1464 HSERYF1 160 XCGAAAAGGUUCA1856TGAACCTTCAAAGCTTTCUGAUGAG 1471 HSERYF1 161 XCGAAAGCUUUGA1857TCAAAGCTTTTGTAAAACUGAUGAG 162AUUUUACACUGAUGAGXCGAAAAGCUUUG1858CAAAGCTTTTGTAAAAT1472HSE RYF1 163UAUUUUACCUGAUGAGXCGAAAAAGCUUU1859AAAGCTTTTGTAAAATA1473HSE RYF1 164UUUUAUUUCUGAUGAGXCGAAACAAAAGC1860GCTTTTGTAAAATAAAA1476HSE RYF1 165GGUGGUUUCUGAUGAGXCGAAAUUUUACA1861TGTAAAATAAAACCACC1481HSE RYF1 166UGGGGGUACUGAUGAGXCGAAAGUGCGCC1862GGCGCACTCTACCCCCA18HUMGA TA2A 20 HUMGATA2A 167 XCGAAAGAGUGCG1863CGCACTCTACCCCCAGCCUGAUGAG 168CAGGGUAGCUGAUGAGXCGAAAGCUGGGG1864CCCCAGCTCCTACCCTG30HUMGA TA2A 33 HUMGATA2A 169 UUACAGGG CUGAUGAG X CGAA AGGAGCUG 1865 CAGCTCCT A CCCTGTAA 170GCGGGGCUCUGAUGAGXCGAAACAGGGUA1866TACCCTGTAAGCCCCGC40HUMGA TA2A 171CACGUCCGCUGAUGAGXCGAAAGGCUGGC1867GCCAGCCTCCGGACGTG55HUMGA TA2A 68 GGGCCCAGCUGAUGAGXCGAAACAGCACG1868CGTGCTGTCCTGGGCCC172 173CCGAGGGCCUGAUGAGXCGAAACGGGCCC1869GGGCCCGTCGCCCTCGG79HUMGA TA2A 85 GGGACCCCCUGAUGAGXCGAAAGGGCGAC1870GTCGCCCTCGGGGTCCC174 Table III. Hammerhead ribozymes targeting TATA transcription factors (1,2,3,4, and 6) and the complementary sequences 175UCCGGCGGCUGAUGAGXCGAAACCCCGAG1871CTCGGGGTCCCGCCGGA91HUMGA TA2A 176GAGUGAAGCUGAUGAGXCGAAAGUUCCGG1872CCGGAACTCCTTCACTC103HUMG ATA2A 177UGAGAGUGCUGAUGAGXCGAAAGGAGUUC1873GAACTCCTTCACTCTCA106HUMG ATA2A 178CUGAGAGUCUGAUGAGXCGAAAAGGAGUU1874AACTCCTTCACTCTCAG107HUMG ATA2A 179GCCUCUGACUGAUGAGXCGAAAGUGAAGG1875CCTTCACTCTCAGAGGC111HUMG ATA2A 180CGGCCUCUCUGAUGAGXCGAAAGAGUGAA1876TTCACTCTCAGAGGCCG113HUMG ATA2A 181AGGGGAGGCUGAUGAGXCGAAACUCGGCC1877GGCCGAGTCCCTCCCCT125HUMG ATA2A 182GGGGAGGGCUGAUGAGXCGAAAGGGACUC1878GAGTCCCTCCCCTCCCC129HUMG ATA2A 183GCCGUGGGCUGAUGAGXCGAAAGGGGAGG1879CCTCCCCTCCCCACGGC134HUMG ATA2A 184GCAGACGCCUGAUGAGXCGAAACGGCCAC1880GTGGCCGTTGCGTCTGC156HUMG ATA2A 185UGGGUGCACUGAUGAGXCGAAACGCAACG1881CGTTGCGTCTGCACCCA161HUMG ATA2A 186GGUGGUGUCUGAUGAGXCGAAAGUCGGGG1882CCCCGACTCACACCACC264HUMG ATA2A 187GUUCCAUGCUGAUGAGXCGAAAGUUGUGC1883GCACAACTACATGGAAC291HUMG ATA2A 188CUCGUCUGCUGAUGAGXCGAAAGGCAGCA1884TGCTGCCTCCAGACGAG317HUMG ATA2A 189UUGAAGAACUGAUGAGXCGAAACGUCCAC1885GTGGACGTCTTCTTCAA334HUMG ATA2A 190GAUUGAAGCUGAUGAGXCGAAAGACGUCC1886GGACGTCTTCTTCAATC336HUMG ATA2A 191UGAUUGAACUGAUGAGXCGAAAAGACGUC1887GACGTCTTCTTCAATCA337HUMG ATA2A 192GGUGAUUGCUGAUGAGXCGAAAGAAGACG1888CGTCTTCTTCAATCACC339HUMG ATA2A 193AGGUGAUUCUGAUGAGXCGAAAAGAAGAC1889GTCTTCTTCAATCACCT340HUMG ATA2A 344 GUCGAGGUCUGAUGAGXCGAAAUUGAAGA1890TCTTCAATCACCTCGAC194 195UGCGAGUCCUGAUGAGXCGAAAGGUGAUU1891AATCACCTCGACTCGCA349HUMG ATA2A 196UGCCCUGCCUGAUGAGXCGAAAGUCGAGG1892CCTOGACTCGCAGGGCA354HUMG ATA2A 197UGGCAUAGCUGAUGAGXCGAAAGGGGUUG1893CAACCCCTACTATGCCA369HUMG ATA2A 198GGUUGGCACUGAUGAGXCGAAAGUAGGGG1894CCCCTACTATGCCAACC372HUMG ATA2A 199GCCGCGCUCUGAUGAGXCGAAAGCGGGGU1895ACCCCGCTCAGCGCGGC386HUMG ATA2A 200CUGUAGGACUGAUGAGXCGAAACGCCGCG1896CGCGGCGTCTCCTACAG397HUMG ATA2A 399 HUMGATA2A 201 XCGAAAGACGCCG1897CGGCGTCTCCTACAGCCCUGAUGAG 402 HUMGATA2A 202 XCGAAAGGAGACG1898CGTCTCCTACAGCCCCGCUGAUGAG 203UGUGCAACCUGAUGAGXCGAAAGUGUGGG1899CCCACACTTGTTGCACA453HUMG ATA2A 456 GGCUGUGCCUGAUGAGXCGAAACAAGUGU1900ACACTTGTTGCACAGCC204 205CCAGGGCACUGAUGAGXCGAAACCCGGGC1901GCCCGGGTTTGCCCTGG470HUMG ATA2A 206GCCAGGGCCUGAUGAGXCGAAAACCCGGG1902CCCGGGTTTGCCCTGGC471HUMG ATA2A 502502HUMGATA2A CUGAUGAGGCCGCAGA X 1903GCAGCCCTCTCTGCGGCAGGGCUGC 504GGGCCGCACUGAUGAGXCGAAAGAGGGCU1904AGCCCTCTCTGCGGCCC208 209UCUUGGAGCUGAUGAGXCGAAAGGGGCUC1905GAGCCCCTTCTCCAAGA540HUMG ATA2A 210GUCUUGGACUGAUGAGXCGAAAAGGGGCU1906AGCCCCTTCTCCAAGAC541HUMG ATA2A 211GCGUCUUGCUGAUGAGXCGAAAGAAGGGG1907CCCCTTCTCCAAGACGC543HUMG ATA2A 212CAGCAGCUCUGAUGAGXCGAAAGGGGUGC1908GCACCCCTCAGCTGCTG564HUMG ATA2A 213UACACAGACUGAUGAGXCGAAAGUGGCCU1909AGGCCACTCTCTGTGTA591HUMG ATA2A 214GGUACACACUGAUGAGXCGAAAGAGUGGC1910GCCACTCTCTGTGTACC593HUMG ATA2A 599599HUMGATA2A 215 XCGAAACACAGAG1911CTCTGTGTACCCAGGGGCUGAUGAG 216AGGCCACUCUGAUGAGXCGAAAGCUCCCG1912CGGGAGCTCAGTGGCCT639HUMG ATA2A 217GGGUGAGGCUGAUGAGXCGAAAGGCCACU1913AGTGGCCTCCCTCACCC648HUMG ATA2A 652 GUAGGGGUCUGAUGAGXCGAAAGGGAGGC1914GCCTCCCTCACCCCTAC218 Table m. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 219GGCUGCUGCUGAUGAGXCGAAAGGGGUGA1915TCACCCCTACAGCAGCC659HUMG ATA2A 220GGGAGCCACUGAUGAGXCGAAAGUGGGCU1916AGCCCACTCTGGCTCCC672HUMG ATA2A 678 HUMGATA2A 221 AAAGGUGG CUGAUGAG X CGAA AGCCAGAG 1917 CTCTGGCT C CCACCTTT 222AAGCCGAACUGAUGAGXCGAAAGGUGGGA1918TCCCACCTTTTCGGCTT685HUMG ATA2A 223GAAGCCGACUGAUGAGXCGAAAAGGUGGG1919CCCACCTTTTCGGCTTC686HUMG ATA2A 224GGAAGCCGCUGAUGAGXCGAAAAAGGUGG1920CCACCTTTTCGGCTTCC687HUMG ATA2A 225GGGAAGCCCUGAUGAGXCGAAAAAAGGUG1921CACCTTTTCGGCTTCCC688HUMG ATA2A 226GUGGUGGGCUGAUGAGXCGAAAGCCGAAA1922TTTCGGCTTCCCACCAC693HUMG ATA2A 227CGUGGUGGCUGAUGAGXCGAAAAGCCGAA1923TTCGGCTTCCCACCACG694HUMG ATA2A 228GGUCAGGACUGAUGAGXCGAAACAGUUCC1924GGAACTGTCTCCTGACC720HUMG ATA2A 229AGGGUCAGCUGAUGAGXCGAAAGACAGUU1925AACTGTCTCCTGACCCT722HUMG ATA2A 230CGUGGUGCCUGAUGAGXCGAAAGGGUCAG1926CTGACCCTAGCACCACG731HUMG ATA2A 231AGGCUGGACUGAUGAGXCGAAACGCUGCC1927GGCAGCGTCTCCAGCCT750HUMG ATA2A 752 HUMGATA2A 232 UGAGGCUG CUGAUGAG X CGAA AGACGCUG 1928 CAGCGTCT C CAGCCTCA 759 HUMGATA2A 233 CGGAAGAU CUGAUGAG X CGAA AGGCUGGA 1929 TCCAGCCT C ATCTTCCG 762 HUMGATA2A 234 CCGCGGAA CUGAUGAG X CGAA AUGAGGCU 1930 AGCCTCAT C TTCCGCGG 235CCCCGCGGCUGAUGAGXCGAAAGAUGAGG1931CCTCATCTTCCGCGGGG764HUMG ATA2A 765 CCCCCGCGCUGAUGAGXCGAAAAGAUGAG1932CTCATCTTCCGCGGGGG236 776 HUMGATA2A 237 GGCUGAAC CUGAUGAG X CGAA ACCCCCCG 1933 CGGGGGGT A GTTCAGCC 238UCGGGCUGCUGAUGAGXCGAAACUACCCC1934GGGGTAGTTCAGCCCGA779HUMG ATA2A 239CUCGGGCUCUGAUGAGXCGAAAACUACCC1935GGGTAGTTCAGCCCGAG780HUMG ATA2A 808 HUMGATA2A 240 UGGUACUU CUGAUGAG X CGAA ACGCCGUC 1936 GACGGCGT C AAGTACCA 813 HUMGATA2A 241 ACGCCUGG CUGAUGAG X CGAA ACUUGACG 1937 CGTCAAGT A CCAGGCGT 822 HUMGATA2A 242 CCGUCAGU CUGAUGAG X CGAA ACGCCUGG 1938 CCAGGCGT C ACTGACGG 857 HUMGATA2A 243 GCGCAGGG CUGAUGAG X CGAA ACGGCCAC 1939 GTGGCCGT C CCCTGCGC 874 HUMGATA2A 244 AUAGUAGC CUGAUGAG X CGAA AGGCCUGG 1940 CCAGGCCT A GCTACTAT 878 HUMGATA2A 245 GCCCAUAG CUGAUGAG X CGAA AGCUAGGC 1941 GCCTAGCT A CTATGGGC 881 HUMGATA2A 246 GGUGCCCA CUGAUGAG X CGAA AGUAGCUA 1942 TAGCTACT A TGGGCACC 899 HUMGATA2A 247 GUGGUGUG CUGAUGAG X CGAA AGCAGGCU 1943 AGCCTGCT A CACACCAC 913 HUMGATA2A 248 UAGGUGGG CUGAUGAG X CGAA AUGGGGUG 1944 CACCCCAT C CCCACCTA 921 HUMGATA2A 249 AGGAGGGG CUGAUGAG X CGAA AGGUGGGG 1945 CCCCACCT A CCCCTCCT 927 HUMGATA2A 250 GCACAUAG CUGAUGAG X CGAA AGGGGUAG 1946 CTACCCCT C CTATGTGC 930 HUMGATA2A 251 CCGGCACA CUGAUGAG X CGAA AGGAGGGG 1947 CCCCTCCT A TGTGCCGG 954 HUMGATA2A 252 CGCUGCUG CUGAUGAG X CGAA AGUCGUGG 1948 CCACGACT A CAGCAGCG 967 HUMGATA2A 253 GGGUGGAA CUGAUGAG X CGAA AGUCOGCU 1949 AGCGGACT C TTCCACCC 969 HUMGATA2A 254 CGGGGUGG CUGAUGAG X CGAA AGAGUCCG 1950 CGGACTCT T CCACCCCG 970 HUMGATA2A 255 CCGGGGUG CUGAUGAG X CGAA AAGAGUCC 1951 GGACTCTT C CACCCCGG 984 HUMGATA2A 256 CCCCCAGG CUGAUGAG X CGAA AGCUCCCG 1952 CGGGAGCT T CCTGGGGG 985 HUMGATA2A 257 CCCCCCAG CUGAUGAG X CGAA AAGCUCCC 1953 GGGAGCTT C CTGGGGGG 1002 HUMGATA2A 258 UGAAGCUG CUGAUGAG X CGAA AGGCCGGU 1954 ACCGGCCT C CAGCTTCA 1008 HUMGATA2A 259 UAGGGGUG CUGAUGAG X CGAA AGCUGGAG 1955 CTCCAGCT T CACCCCTA 1009 HUMGATA2A 260 UUAGGGGU CUGAUGAG X CGAA AAGCUGGA 1956 TCCAGCTT C ACCCCTAA 1016 HUMGATA2A 261 GCGCUGCU CUGAUGAG X CGAA AGGGGUGA 1957 TCACCCCT A AGCAGCGC 1034 HUMGATA2A 262 ACAGGAAC CUGAUGAG X CGAA AGUCUUGC 1958 GCAAGACT C GTTCCTGT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 263UGAACAGGCUGAUGAGXCGAAACGAGUCU1959AGACTCGTTCCTGTTCA1037HUM GATA2A 264CUGAACAGCUGAUGAGXCGAAAACGAGUC1960GACTCGTTCCTGTTCAG1038HUM GATA2A 265GCCUUCUGCUGAUGAGXCGAAACAGGAAC1961GTTCCTGTTCAGAAGGC1043HUM GATA2A 266GGCCUUCUCUGAUGAGXCGAAAACAGGAA1962TTCCTGTTCAGAAGGCC1044HUM GATA2A 1063 CCACAGUUCUGAUGAGXCGAAACACACUC1963GAGTGTGTCAACTGTGG267 268CCGCCAGACUGAUGAGXCGAAAGGGGUUG1964CAACCCCTCTCTGGCGG1088HUM GATA2A 1090 HUMGATA2A 269 CGCCGCCA CUGAUGAG X CGAA AGAGGGGU 1965 ACCCCTCT C TGGCGGCG 270UGCACAGGCUGAUGAGXCGAAAGUGGCCG1966CGGCCACTACCTGTGCA1116HUM GATA2A 271UGUGGUAGCUGAUGAGXCGAAAGCCGCAG1967CTGCGGCTTCTACCACA1137HUM GATA2A 272UUGUGGUACUGAUGAGXCGAAAAGCCGCA1968TGCGGCTTCTACCACAA1138HUM GATA2A 273UCUUGUGGCUGAUGAGXCGAAAGAAGCCG1969CGGCTTCTACCACAAGA1140HUM GATA2A 274GGCUUGAUCUGAUGAGXCGAAAGUGGUCG1970CGACCACTCATCAAGCC1171HUM GATA2A 275UUGGGCUUCUGAUGAGXCGAAAUGAGUGG1971CCACTCATCAAGCCCAA1174HUM GATA2A 276UGGCGGCCCUGAUGAGXCGAAACAGUCUU1972AAGACTGTCGGCCGCCA1194HUM GATA2A 277AUUUGCACCUGAUGAGXCGAAACAGGUGC1973GCACCTGTTGTGCAAAT1220HUM GATA2A 1229 CGUCUGACCUGAUGAGXCGAAAUUUGCAC1974GTGCAAATTGTCAGACG278 279UGUCGUCUCUGAUGAGXCGAAACAAUUUG1975CAAATTGTCAGACGACA1232HUM GATA2A 1251 HUMGATA2A 280 GGCGCCAU CUGAUGAG X CGAA AGGUGGUG 1976 CACCACCT T ATGGCGCC 1252 HUMGATA2A 281 CGGCGCCA CUGAUGAG X CGAA AAGGUGGU 1977 ACCACCTT A TGGCGCCG 1282 HUMGATA2A 282 GCGUUGCA CUGAUGAG X CGAA ACAGGGUC 1978 GACCCTGT C TGCAACGC 1300 HUMGATA2A 283 UUGUAGUA CUGAUGAG X CGAA AGGCCACA 1979 TGTGGCCT C TACTACAA 1302 HUMGATA2A 284 GCUUGUAG CUGAUGAG X CGAA AGAGGCCA 1980 TGGCCTCT A CTACAAGC 1305 HUMGATA2A 285 GCAGCUUG CUGAUGAG X CGAA AGUAGAGG 1981 CCTCTACT A CAAGCTGC 1321 HUMGATA2A 286 GGCCUGUU CUGAUGAG X CGAA ACAUUGUG 1982 CACAATGT T AACAGGCC 1322 HUMGATA2A 287 UGGCCUGU CUGAUGAG X CGAA AACAUUGU 1983 ACAATGTT A ACAGGCCA 1354 HUMGATA2A 288 CGAGUCUG CUGAUGAG X CGAA AUCCCUUC 1984 GAAGGGAT C CAGACTCG 1361 HUMGATA2A 289 CCGGUUCC CUGAUGAG X CGAA AGUCUGGA 1985 TCCAGACT C GGAACCGG 1377 HUMGATA2A 290 ACUUGUUG CUGAUGAG X CGAA ACAUCUUC 1986 GAAGATGT C CAACAAGT 1386 HUMGATA2A 291 UCUUCUUG CUGAUGAG X CGAA ACUUGUUG 1987 CAACAAGT C CAAGAAGA 1416 HUMGATA2A 292 GCUCCUCG CUGAUGAG X CGAA AGCACUCC 1988 GGAGTGCT T CGAGGAGC 1417 HUMGATA2A 293 AGCUCCUC CUGAUGAG X CGAA AAGCACUC 1989 GAGTGCTT C GAGGAGCT 1428 HUMGATA2A 294 UGCACUUU CUGAUGAG X CGAA ACAGCUCC 1990 GGAGCTGT C AAAGTGCA 1449 HUMGATA2A 295 AGGGGGAU CUGAUGAG X CGAA ACUUCUCC 1991 GGAGAAGT C ATCCCCCT 1452 HUMGATA2A 296 UGAAGGGG CUGAUGAG X CGAA AUGACUUC 1992 GAAGTCAT C CCCCTTCA 1458 HUMGATA2A 297 CUGCACUG CUGAUGAG X CGAA AGGGGGAU 1993 ATCCCCCT T CAGTGCAG 1459 HUMGATA2A 298 GCUGCACU CUGAUGAG X CGAA AAGGGGGA 1994 TCCCCCTT C AGTGCAGC 1493 HUMGATA2A 299 GUGGCCCA CUGAUGAG X CGAA AGGUGCCA 1995 TGGCACCT A TGGGCCAC 1504 HUMGATA2A 300 AAGGGCGG CUGAUGAG X CGAA AGGUGGCC 1996 GGCCACCT C CCGCCCTT 1512 HUMGATA2A 301 AGUGGCUG CUGAUGAG X CGAA AGGGCGGG 1997 CCCGCCCT T CAGCCACT 1513 HUMGATA2A 302 GAGUGGCU CUGAUGAG X CGAA AAGGGCGG 1998 CCGCCCTT C AGCCACTC 1521 HUMGATA2A 303 UGUGUCCG CUGAUGAG X CGAA AGUGGCUG 1999 CAGCCACT C CGGACACA 1531 HUMGATA2A 304 GUGGGCAG CUGAUGAG X CGAA AUGUGUCC 2000 GGACACAT C CTGCCCAC 1541 HUMGATA2A 305 GGGCGUCG CUGAUGAG X CGAA AGUGGGCA 2001 TGCCCACT C CGACGCCC 1552 HUMGATA2A 306 GAGGGGUG CUGAUGAG X CGAA AUGGGCGU 2002 ACGCCCAT C CACCCCTC Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 307GGCUGGAGCUGAUGAGXCGAAAGGGGUGG3003CCACCCCTCCTCCAGCC1560HUM GATA2A 308AGAGGCUGCUGAUGAGXCGAAAGGAGGGG2004CCCCTCCTCCAGCCTCT1563HUM GATA2A 309CCGAAGGACUGAUGAGXCGAAAGGCUGGA2005TCCAGCCTCTCCTTCGG1570HUM GATA2A 1572 GGCCGAAGCUGAUGAGXCGAAAGAGGCUG2006CAGCCTCTCCTTCGGCC310 311GGUGGCCGCUGAUGAGXCGAAAGGAGAGG2007CCTCTCCTTCGGCCACC1575HUM GATA2A 312GGGUGGCCCUGAUGAGXCGAAAAGGAGAG2008CTCTCCTTCGGCCACCC1576HUM GATA2A 313CCAUGCUGCUGAUGAGXCGAAACGGGUGG2009CCACCCGTCCAGCATGG1593HUM GATA2A 314CUGUUCCCCUGAUGAGXCGAAACCCCAUG2010CATGGGGTAGGGAACAG1617HUM GATA2A 315CGGUCCUCCUGAUGAGXCGAAACGUCCGU2011ACGGACGTCGAGGACCG1634HUM GATA2A 316CAUCCCGGCUGAUGAGXCGAAAGUGCCCG2012CGGGCACTCCCGGGATG1649HUM GATA2A 317GGGCUGGUCUGAUGAGXCGAAAGGGUUUG2013CAAACCCTTACCAGCCC1673HUM GATA2A 1674 HUMGATA2A 318 UGGGCUGG CUGAUGAG X CGAA AAGGGUUU 2014 AAACCCTT A CCAGCCCA 319GUUCGGGACUGAUGAGXCGAAAUGCUGGG2015CCCAGCATTTCCCGAAC1687HUM GATA2A 1688 HUMGATA2A 320 GGUUCGGG CUGAUGAG X CGAA AAUGCUGG 2016 CCAGCATT T CCCGAACC 1689 HUMGATA2A 321 GGGUUCGG CUGAUGAG X CGAA AAAUGCUG 2017 CAGCATTT C CCGAACCC 1708 HUMGATA2A 322 GCUGGCAG CUGAUGAG X CGAA AGUGGUGU 2018 ACACCACT C CTGCCAGC 1724 HUMGATA2A 323 GCUGGGCC CUGAUGAG X CGAA AGCCCGGG 2019 CCCGGGCT C GGCCCAGC 1740 HUMGATA2A 324 CUCCAGGA CUGAUGAG X CGAA AGGGGGUG 2020 CACCCCCT C TCCTGGAG 1742 HUMGATA2A 325 CCCUCCAG CUGAUGAG X CGAA AGAGGGGG 2021 CCCCCTCT C CTGGAGGG 1775 HUMGATA2A 326 UUCACAGU CUGAUGAG X CGAA ACUGCUGG 2022 CCAGCAGT T ACTGTGAA 327AUUCACAGCUGAUGAGXCGAAAACUGCUG2023CAGCAGTTACTGTGAAT1776HUM GATA2A 328CGGUGGGGCUGAUGAGXCGAAACAUUCAC2024GTGAATGTTCCCCACCG1787HUM GATA2A 329GCGGUGGGCUGAUGAGXCGAAAACAUUCA2025TGAATGTTCCCCACCGC1788HUM GATA2A 1810 HUMGATA2A 330 CAGGUGCG CUGAUGAG X CGAA AGGCAGCC 2026 GGCTGCCT C CGCACCTG 1838 HUMGATA2A 331 AUGCAGGA CUGAUGAG X CGAA ACCCCACC 2027 GGTGGGGT T TCCTGCAT 1839 HUMGATA2A 332 CAUGCAGG CUGAUGAG X CGAA AACCCCAC 2028 GTGGGGTT T CCTGCATG 1840 HUMGATA2A 333 CCAUGCAG CUGAUGAG X CGAA AAACCCCA 2029 TGGGGTTT C CTGCATGG 1854 HUMGATA2A 334 CUCCAAAC CUGAUGAG X CGAA ACUGUCCA 2030 TGGACAGT T GTTTGGAG 1857 HUMGATA2A 335 GUUCUCCA CUGAUGAG X CGAA ACAACUGU 2031 ACAGTTGT T TGGAGAAC 1858 HUMGATA2A 336 UGUUCUCC CUGAUGAG X CGAA AACAACUG 2032 CAGTTGTT T GGAGAACA 1879 HUMGATA2A 337 UCUACAUA CUGAUGAG X CGAA AGUUGUCC 2033 GGACAACT T TATGTAGA 1880 HUMGATA2A 338 CUCUACAU CUGAUGAG X CGAA AAGUUGUC 2034 GACAACTT T ATGTAGAG 1881 HUMGATA2A 339 UCUCUACA CUGAUGAG X CGAA AAAGUUGU 2035 ACAACTTT A TGTAGAGA 1885 HUMGATA2A 340 CUUUUCUC CUGAUGAG X CGAA ACAUAAAG 2036 CTTTATGT A GAGAAAAG 1923 HUMGATA2A 341 CUUCUAAA CUGAUGAG X CGAA AUGGUUGC 2037 GCAACCAT T TTTAGAAG 1924 HUMGATA2A 342 CCUUCUAA CUGAUGAG X CGAA AAUGGUUG 2038 CAACCATT T TTAGAAGG 1925 HUMGATA2A 343 UCCUUCUA CUGAUGAG X CGAA AAAUGGUU 2039 AACCATTT T TAGAAGGA 1926 HUMGATA2A 344 UUCCUUCU CUGAUGAG X CGAA AAAAUGGU 2040 ACCATTTT T AGAAGGAA 1927 HUMGATA2A 345 UUUCCUUC CUGAUGAG X CGAA AAAAAUGG 2041 CCATTTTT A GAAGGAAA 1942 HUMGATA2A 346 UUUUGCCU CUGAUGAG X CGAA AUCCUUUU 2042 AAAAGGAT T AGGCAAAA 1943 HUMGATA2A 347 UUUUUGCC CUGAUGAG X CGAA AAUCCUUU 2043 AAAGGATT A GGCAAAAA 1953 HUMGATA2A 348 AAAUAAAU CUGAUGAG X CGAA AUUUUUGC 2044 GCAAAAAT A ATTTATTT 1956 HUMGATA2A 349 GCAAAAUA CUGAUGAG X CGAA AUUAUUUU 2045 AAAATAAT T TATTTTGC 1957 HUMGATA2A 350 AGCAAAAU CUGAUGAG X CGAA AAUUAUUU 2046 AAATAATT T ATTTTGCT Table in. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 351GAGCAAAACUGAUGAGXCGAAAAAUUAUU2047AATAATTTATTTTGCTC1958HUM GATA2A 352AAGAGCAACUGAUGAGXCGAAAUAAAUUA2048TAATTTATTTTGCTCTT1960HUM GATA2A 353CAAGAGCACUGAUGAGXCGAAAAUAAAUU2049AATTTATTTTGCTCTTG1961HUM GATA2A 354ACAAGAGCCUGAUGAGXCGAAAAAUAAAU2050ATTTATTTTGCTCTTGT1962HUM GATA2A 355AGAAACAACUGAUGAGXCGAAAGCAAAAU2051ATTTTGCTCTTGTTTCT1966HUM GATA2A 356UUAGAAACCUGAUGAGXCGAAAGAGCAAA2052TTTGCTCTTGTTTCTAA1968HUM GATA2A 358CUUGUUAGCUGAUGAGXCGAAAACAAGAG2054CTCTTGTTTCTAACAAG1972HUM GATA2A 359CCUUGUUACUGAUGAGXCGAAAAACAAGA2055TCTTGTTTCTAACAAGG1973HUM GATA2A 360AGCCUUGUCUGAUGAGXCGAAAGAAACAA2056TTGTTTCTAACAAGGCT1975HUM GATA2A 1984 HUMGATA2A 361 AAGUUUCC CUGAUGAG X CGAA AGCCUUGU 2057 ACAAGGCT T GGAAACTT 1992 HUMGATA2A 362 AGACCACC CUGAUGAG X CGAA AGUUUCCA 2058 TGGAAACT T GGTGGTCT 1999 HUMGATA2A 363 AUAGCUCA CUGAUGAG X CGAA ACCACCAA 2059 TTGGTGGT C TGAGCTAT 2006 HUMGATA2A 364 ACUUGGGA CUGAUGAG X CGAA AGCUCAGA 2060 TCTGAGCT A TCCCAAGT 2008 HUMGATA2A 365 AGACUUGG CUGAUGAG X CGAA AUAGCUCA 2061 TGAGCTAT C CCAAGTCT 2015 HUMGATA2A 366 GAACCGGA CUGAUGAG X CGAA ACUUGGGA 2062 TCCCAAGT C TCCGGTTC 2017 HUMGATA2A 367 AAGAACCG CUGAUGAG X CGAA AGACUUGG 2063 CCAAGTCT C CGGTTCTT 2022 HUMGATA2A 368 CGAGGAAG CUGAUGAG X CGAA ACCGGAGA 2064 TCTCCGGT T CTTCCTCG 2023 HUMGATA2A 369 CCGAGGAA CUGAUGAG X CGAA AACCGGAG 2065 CTCCGGTT C TTCCTCGG 2025 HUMGATA2A 370 UCCCGAGG CUGAUGAG X CGAA AGAACCGG 2066 CCGGTTCT T CCTCGGGA 2026 HUMGATA2A 371 AUCCCGAG CUGAUGAG X CGAA AAGAACCG 2067 CGGTTCTT C CTCGGGAT 2029 HUMGATA2A 372 CCAAUCCC CUGAUGAG X CGAA AGGAAGAA 2068 TTCTTCCT C GGGATTGG 2035 HUMGATA2A 373 GACCCGCC CUGAUGAG X CGAA AUCCCGAG 2069 CTCGGGAT T GGCGGGTC 2043 HUMGATA2A 374 GGCAAGUG CUGAUGAG X CGAA ACCCGCCA 2070 TGGCGGGT C CACTTGCC 2048 HUMGATA2A 375 GCCCUGGC CUGAUGAG X CGAA AGUGGACC 2071 GGTCCACT T GCCAGGGC 2058 HUMGATA2A 376 UGCCCCCA CUGAUGAG X CGAA AGCCCUGG 2072 CCAGGGCT C TGGGGGCA 2070 HUMGATA2A 377 UCCCCACA CUGAUGAG X CGAA AUCUGCCC 2073 GGGCAGAT T TGTGGGGA 2071 HUMGATA2A 378 GUCCCCAC CUGAUGAG X CGAA AAUCUGCC 2074 GGCAGATT T GTGGGGAC 2082 HUMGATA2A 379 UGCAGGCU CUGAUGAG X CGAA AGGUCCCC 2075 GGGGACCT C AGCCTGCA 2095 HUMGATA2A 380 GAGGAGAA CUGAUGAG X CGAA AGGGUGCA 2076 TGCACCCT C TTCTCCTC 2097 HUMGATA2A 381 CAGAGGAG CUGAUGAG X CGAA AGAGGGUG 2077 CACCCTCT T CTCCTCTG 2098 HUMGATA2A 382 CCAGAGGA CUGAUGAG X CGAA AAGAGGGU 2078 ACCCTCTT C TCCTCTGG 2100 HUMGATA2A 383 AGCCAGAG CUGAUGAG X CGAA AGAAGAGG 2079 CCTCTTCT C CTCTGGCT 2103 HUMGATA2A 384 GGAAGCCA CUGAUGAG X CGAA AGGAGAAG 2080 CTTCTCCT C TGGCTTCC 2109 HUMGATA2A 385 AGAGAGGG CUGAUGAG X CGAA AGCCAGAG 2081 CTCTGGCT T CCCTCTCT 2110 HUMGATA2A 386 CAGAGAGG CUGAUGAG X CGAA AAGCCAGA 2082 TCTGGCTT C CCTCTCTG 2114 HUMGATA2A 387 AUUUCAGA CUGAUGAG X CGAA AGGGAAGC 2083 GCTTCCCT C TCTGAAAT 2116 HUMGATA2A 388 CUAUUUCA CUGAUGAG X CGAA AGAGGGAA 2084 TTCCCTCT C TGAAATAG 2123 HUMGATA2A 389 AGUUCGGC CUGAUGAG X CGAA AUUUCAGA 2085 TCTGAAAT A GCCGAACT 2132 HUMGATA2A 390 CCAGCCUG CUGAUGAG X CGAA AGUUCGGC 2086 GCCGAACT C CAGGCTGG 2193 HUMGATA2A 391 GGCCGUCA CUGAUGAG X CGAA AGCAGGCA 2087 TGCCTGCT T TGACGGCC 2194 HUMGATA2A 392 UGGCCGUC CUGAUGAG X CGAA AAGCAGGC 2088 GCCTGCTT T GACGGCCA 2225 HUMGATA2A 393 CCGCCGGU CUGAUGAG X CGAA AUUGUCUC 2089 GAGACAAT C ACCGGCGG 2235 HUMGATA2A 394 UCCUGCAG CUGAUGAG X CGAA ACCGCCGG 2090 CCGGCGGT C CTGCAGGA Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 395CGAGCUCGCUGAUGAGXCGAAAUUCCUGC2091GCAGGAATTCGAGCTCG2246HUM GATA2A 396CCGAGCUCCUGAUGAGXCGAAAAUUCCUG2092CAGGAATTCGAGCTCGG2247HUM GATA2A 397AGGGUACCCUGAUGAGXCGAAAGCUCGAA2093TTCGAGCTCGGTACCCT2253HUM GATA2A 398UUGCAGGGCUGAUGAGXCGAAACCGAGCU2094AGCICGGTACCCTGCAA2257HUM GATA2A 399GGCCUGGGCUGAUGAGXCGAAAUCUGUUC2095CAACAGATTCCCAGGCC2271HUM GATA2A 400UGGCCUGGCUGAUGAGXCGAAAAUCUGUU2096AACAGATTCCCAGGCCA2272HUM GATA2A 401CUUCCUGUCUGAUGAGXCGAAACCCAGCC2097GGCTGGGTCACAGGAAG2290HUM GATA2A 402UUCAAGAACUGAUGAGXCGAAAUGUUGUU2098AACAACATTTTCTTGAA2309HUM GATA2A 403UUUCAAGACUGAUGAGXCGAAAAUGUUGU2099ACAACATTTTCTTGAAA2310HUM GATA2A 404CUUUCAAGCUGAUGAGXCGAAAAAUGUUG2100CAACATTTTCTTGAAAG2311HUM GATA2A 405CCUUUCAACUGAUGAGXCGAAAAAAUGUU2101AACATTTTCTTGAAAGG2312HUM GATA2A 406CCCCUUUCCUGAUGAGXCGAAAGAAAAUG2102CATTTTCTTGAAAGGGG2314HUM GATA2A 2329 HUMGATA2A 407 GAUCUGGA CUGAUGAG X CGAA ACGUUUCC 2103 GGAAACGT T TCCAGATC 2330 HUMGATA2A 408 GGAUCUGG CUGAUGAG X CGAA AACGUUUC 2104 GAAACGTT T CCAGATCC 409AGGAUCUGCUGAUGAGXCGAAAAACGUUU2105AAACGTTTCCAGATCCT2331HUM GATA2A 410AGGGACAGCUGAUGAGXCGAAAUCUGGAA2106TTCCAGATCCTGTCCCT2337HUM GATA2A 411GCCAAAGGCUGAUGAGXCGAAACAGGAUC2107GATOCTGTCCCTTTGGC2342HUM GATA2A 412CAAAGCCACUGAUGAGXCGAAAGGGACAG2108CTGTCCCTTTGGCTTTG2346HUM GATA2A 413UCAAAGCCCUGAUGAGXCGAAAAGGGACA2109TGTCCCTTTGGCTTTGA2347HUM GATA2A 2352 HUMGATA2A 414 CGGCCUCA CUGAUGAG X CGAA AGCCAAAG 2110 CTTTGGCT T TGAGGCCG 2353 HUMGATA2A 415 UCGGCCUC CUGAUGAG X CGAA AAGCCAAA 2111 TTTGGCTT T GAGGCCGA 2379 HUMGATA2A 416 GUAAAGGG CUGAUGAG X CGAA ACACAGUC 2112 GACTGTGT C CCCTTTAC 2384 HUMGATA2A 417 GCUCAGUA CUGAUGAG X CGAA AGGGGACA 2113 TGTCCCCT T TACTGAGC 2385 HUMGATA2A 418 CGCUCAGU CUGAUGAG X CGAA AAGGGGAC 2114 GTCCCCTT T ACTGAGCG 2386 HUMGATA2A 419 GCGCUCAG CUGAUGAG X CGAA AAAGGGGA 2115 TCCCCTTT A CTGAGCGC 2408 HUMGATA2A 420 CCUGAGAA CUGAUGAG X CGAA ACAGGCUG 2116 CAGCCTGT C TTCTCAGG 2410 HUMGATA2A 421 CACCUGAG CUGAUGAG X CGAA AGACAGGC 2117 GCCTGTCT T CTCAGGTG 2411 HUMGATA2A 422 CCACCUGA CUGAUGAG X CGAA AAGACAGG 2118 CCTGTCTT C TCAGGTGG 2413 HUMGATA2A 423 GUCCACCU CUGAUGAG X CGAA AGAAGACA 2119 TGTCTTCT C AGGTGGAC 2428 HUMGATA2A 424 GALCUAUU CUGAUGAG X CGAA ACAUGGGU 2120 ACCCATGT A AATAGATC 2432 HUMGATA2A 425 AAAGGAUD CUGAUGAG X CGAA AUUUACAU 2121 ATGTAAAT A GATCCTTT 2436 HUMGATA2A 426 AGAAAAAG CUGAUGAG X CGAA AUCUAUUU 2122 AAATAGAT C CTTTTTCT 2439 HUMGATA2A 427 AGCAGAAA CUGAUGAG X CGAA AGGAUCUA 2123 TAGATCCT T TTTCTGCT 2440 HUMGATA2A 428 UAGCAGAA CUGAUGAG X CGAA AAGGAUCU 2124 AGATOCTT T TTCTGCTA 2441 HUMGATA2A 429 UUAGCAGA CUGAUGAG X CGAA AAAGGAUC 2125 GATCCTTT T TCTGCTAA 2442 HUMGATA2A 430 GUUAGCAG CUGAUGAG X CGAA AAAAGGAU 2126 ATCCTTTT T CTGCTAAC 2443 HUMGATA2A 431 GGUUAGCA CUGAUGAG X CGAA AAAAAGGA 2127 TCCTTTTT C TGCTAACC 2448 HUMGATA2A 432 UGAAGGGU CUGAUGAG X CGAA AGCAGAAA 2128 TTTCTGCT A ACCCTTCA 2454 HUMGATA2A 433 UGGGGUUG CUGAUGAG X CGAA AGGGUUAG 2129 CTAACCCT T CAACCCCA 2455 HUMGATA2A 434 CUGGGGUU CUGAUGAG X CGAA AAGGGUUA 2130 TAACCCTT C AACCCCAG 2474 HUMGATA2A 435 CCAGUCAG CUGAUGAG X CGAA ACACAGCC 2131 GGCTGTGT C CTGACTGG 2485 HUMGATA2A 436 GGACCUGA CUGAUGAG X CGAA ACCCAGUC 2132 GACTGGGT C TCAGGTCC 2487 HUMGATA2A 437 CUGGACCU CUGAUGAG X CGAA AGACCCAG 2133 CTGGGTCT C AGGTCCAG 2492 HUMGATA2A 438 AAAGUCUG CUGAUGAG X CGAA ACCUGAGA 2134 TCTCAGGT C CAGACTTT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 439CCACAGUACUGAUGAGXCGAAAGUCUGGA2135TCCAGACTTTACTGTGG2499HUM GATA2A 440GCCACAGUCUGAUGAGXCGAAAAGUCUGG2136CCAGACTTTACTGTGGC2500HUM GATA2A 441AGCCACAGCUGAUGAGXCGAAAAAGUCUG2137CAGACTTTACTGTGGCT2501HUM GATA2A 442UUGGGAAGCUGAUGAGXCGAAAUCCACAG2138CTGTGGATCCTTCCCAA2516HUM GATA2A 443ACCUUGGGCUGAUGAGXCGAAAGGAUCCA2139TGGATCCTTCCCAAGGT2519HUM GATA2A 444UACCUUGGCUGAUGAGXCGAAAAGGAUCC2140GGATCCTTCCCAAGGTA2520HUM GATA2A 445UACAGCUGCUGAUGAGXCGAAACCUUGGG2141CCCAAGGTACAGCTGTA2528HUM GATA2A 446CGUUUAUACUGAUGAGXCGAAACAGCUGU2142ACAGCTGTATATAAACG2536HUM GATA2A 447CACGUUUACUGAUGAGXCGAAAUACAGCU2143AGCTGTATATAAACGTG2538HUM GATA2A 2540 HUMGATA2A 448 XCGAAAUAUACAG2144CTGTATATAAACGTGTCCUGAUGAG 449AAGCUCGGCUGAUGAGXCGAAACACGUUU2145AAACGTGTCCCGAGCTT2548HUM GATA2A 450CAGAAUCUCUGAUGAGXCGAAAGCUCGGG2146CCCGAGCTTAGATTCTG2556HUM GATA2A 451ACAGAAUCCUGAUGAGXCGAAAAGCUCGG2147CCGAGCTTAGATTCTGT2557HUM GATA2A 452GCAUACAGCUGAUGAGXCGAAAUCUAAGC2148GCTTAGATTCTGTATGC2561HUM GATA2A 453CGCAUACACUGAUGAGXCGAAAAUCUAAG2149CTTAGATTCTGTATGCG2562HUM GATA2A 454UCACCGCACUGAUGAGXCGAAACAGAAUC2150GATTCTGTATGCGGTGA2566HUM GATA2A 10 HUMGATA2A 455 GGGAUGGG CUGAUGAG X CGAA AGGCUGGG 2151 CCCAGCCT T CCCATCCC 11 HUMGATA2A 456 GGGGAUGG CUGAUGAG X CGAA AAGGCUGG 2152 CCAGCCTT C CCATCCCC 16 HUMGATA2A 457 GGUGGGGG CUGAUGAG X CGAA AUGGGAAG 2153 CTTCCCAT C CCCCCACC 35 HUMGATA2A 458 CGUUGAAU CUGAUGAG X CGAA AUUUGCUU 2154 AAGCAAAT C ATTCAACG 38 HUMGATA2A 459 GGUCGUUG CUGAUGAG X CGAA AUGAUUUG 2155 CAAATCAT T CAACGACC 39 HUMGATA2A 460 GGGUCGUU CUGAUGAG X CGAA AAUGAUUU 2156 AAATCATT C AACGACCC 56 HUMGATA2A 461 UGCCGUCG CUGAUGAG X CGAA AGGGUCGG 2157 CCGACCCT C CGACGGCA 80 HUMGATA2A 462 CCGCCUGG CUGAUGAG X CGAA AGGUCGGG 2158 CCCGACCT C CCAGGCGG 97 HUMGATA2A 463 GGGGAGGG CUGAUGAG X CGAA AGGGCGGU 2159 ACCGCCCT T CCCTCCCC 98 HUMGATA2A 464 CGGGGAGG CUGAUGAG X CGAA AAGGGCGG 2160 CCGCCCTT C CCTCCCCG 102 HUMGATA2A 465 CGCGCGGG CUGAUGAG X CGAA AGGGAAGG 2161 CCTTCCCT C CCCGCGCG 114 HUMGATA2A 466 GGGCCCGG CUGAUGAG X CGAA ACCCGCGC 2162 GCGCGGGT T CCGGGCCC 115 HUMGATA2A 467 CGGGCCCG CUGAUGAG X CGAA AACCCGCG 2163 CGCGGGTT C CGGGCCCG 208 HUMGATA2A 468 UGCCCGUU CUGAUGAG X CGAA AGCACGGC 2164 GCCGTGCT C AACGGGCA 244 HUMGATA2A 469 GAGUGGCU CUGAUGAG X CGAA AGGCCCGG 2165 CCGGGCCT C AGCCACTC 252 HUMGATA2A 470 CCAUGUAG CUGAUGAG X CGAA AGUGGCUG 2166 CAGCCACT C CTACATGG 255 HUMGATA2A 471 CGUCCAUG CUGAUGAG X CGAA AGGAGUGG 2167 CCACTCCT A CATGGACG 273 HUMGATA2A 472 GCAGCGGG CUGAUGAG X CGAA ACUGCGCC 2168 GGCGCAGT A CCCGCTGC 301 HUMGATA2A 473 AUGUUAAA CUGAUGAG X CGAA AGCACAUC 2169 GATGTGCT T TTTAACAT 302 HUMGATA2A 474 GAUGUUAA CUGAUGAG X CGAA AAGCACAU 2170 ATGTGCTT T TTAACATC 303 HUMGATA2A 475 CGAUGUUA CUGAUGAG X CGAA AAAGCACA 2171 TGTGCTTT T TAACATCG 304 HUMGATA2A 476 UCGAUGUU CUGAUGAG X CGAA AAAAGCAC 2172 GTGCTTTT T AACATCGA 305 HUMGATA2A 477 GUCAGUGU CUGAUGAG X CGAA AAAAAGCA 2173 TGCTTTTT A ACATCGAC 310 HUMGATA2A 478 UGACCGUC CUGAUGAG X CGAA AUGUUAAA 2174 TTTAACAT C GACGGTCA 317 HUMGATA2A 479 GUUGCCUU CUGAUGAG X CGAA ACCGUCGA 2175 TCGACGGT C AAGGCAAC 331 HUMGATA2A 480 UAGGGCGG CUGAUGAG X CGAA ACGUGGUU 2176 AACCACGT C CCGCCCTA 339 HUMGATA2A 481 UUCCGUAG CUGAUGAG X CGAA AGGGCGGG 2177 CCCGCCCT A CTACGGAA 342 HUMGATA2A 482 AGUUUCCG CUGAUGAG X CGAA AGUAGGGC 2178 GCCCTACT A CGGAAACT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3, 4, and 6) and the complementary sequences 483CCCUGACCCUGAUGAGXCGAAAGUUUCCG2179CGGAAACTCGGTCAGGG351HSGA TA3R 484GUGGCCCUCUGAUGAGXCGAAACCGAGUU2180AACTCGGTCAGGGCCAC355HSGA TA3R 485UCGGAGGGCUGAUGAGXCGAAACCUCUGC2181GCAGAGGTACCCTCCGA375HSGA TA3R 486GUGGGUCGCUGAUGAGXCGAAAGGGUACC2182GGTACCCTCCGACCCAC380HSGA TA3R 487AUGAAGCACUGAUGAGXCGAAAGGCGGGC2183GCCCGCCTCTGCTTCAT416HSGA TA3R 488GAUCCAUGCUGAUGAGXCGAAAGCAGAGG2184CCTCTGCTTCATGGATC421HSGA TA3R 489GGAUCCAUCUGAUGAGXCGAAAAGCAGAG2185CTCTGCTTCATGGATCC422HSGA TA3R 490AGGGUAGGCUGAUGAGXCGAAAUCCAUGA2186TCATGGATCCCTACCCT429HSGA TA3R 491AGCCAGGGCUGAUGAGXCGAAAGGGAUCC2187GGATCCCTACCCTGGCT433HSGA TA3R 492UCCAGGGGCUGAUGAGXCGAAAGGCGGUG2188CACCGCCTCCCCCTGGA480HSGA TA3R 493GGGGCUGACUGAUGAGXCGAAAUUCCAGG2189CCTGGAATCTCAGCCCC491HSGA TA3R 494AAGGGGCUCUGAUGAGXCGAAAGAUUCCA2190TGGAATCTCAGCCCCTT493HSGA TA3R 495UCUUGGAGCUGAUGAGXCGAAAGGGGCUG2191CAGCCCCTTCTCCAAGA501HSGA TA3R 502 GUCUUGGACUGAUGAGXCGAAAAGGGGCU2192AGCCCCTTCTCCAAGAC496 497ACGUCUUGCUGAUGAGXCGAAAGAAGGGG2193CCCCTTCTCCAAGACGT504HSGA TA3R 513513HSGATA3R 498 XCGAAACGUCUUG2194CAAGACGTCCATCCACCCUGAUGAG 499CCGUGGUGCUGAUGAGXCGAAAUGGACGU2195ACGTCCATCCACCACGG517HSGA TA3R 500GCCCCGGGCUGAUGAGXCGAAAGCCGUGG2196CCACGGCTCCCCGGGGC528HSGA TA3R 501UAGACGGACUGAUGAGXCGAAAGGGGCCC2197GGGCCCCTCTCCGTCTA541HSGA TA3R 502GGUAGACGCUGAUGAGXCGAAAGAGGGGC2198GCCCCTCTCCGTCTACC543HSGA TA3R 503GGGGGGUACUGAUGAGXCGAAACGGAGAG2199CTCTCCGTCTACCCCCC547HSGA TA3R 549 HSGATA3R 504 XCGAAAGACGGAG2200CTCCGTCTACCCCCCGGCUGAUGAG 505AGGAGGACCUGAUGAGXCGAAAGGCCGGG2201CCCGGCCTCGTCCTCCT561HSGA TA3R 506AGGAGGAGCUGAUGAGXCGAAACGAGGCC2202GGCCTCGTCCTCCTCCT564HSGA TA3R 567 ACAAGGAGCUGAUGAGXCGAAAGGACGAG2203CTCGTOCTCCTCCTTGT507 508CCGACAAGCUGAUGAGXCGAAAGGAGGAC2204GTCCTCCTCCTTGTCGG570HSGA TA3R 509CCCCCGACCUGAUGAGXCGAAAGGAGGAG2205CTCCTCCTTGTCGGGGG573HSGA TA3R 510GGCCCCCCCUGAUGAGXCGAAACAAGGAG2206CTCCTTGTCGGGGGGCC576HSGA TA3R 511AAGGUGAACUGAUGAGXCGAAAGGUGCGG2207CCGCACCTCTTCACCTT601HSGA TA3R 512GGAAGGUGCUGAUGAGXCGAAAGAGGUCC2208GCACCTCTTCACCTTCC603HSGA TA3R 513GGGAAGGUCUGAUGAGXCGAAAACAGGUG2209CACCTCTTCACCTTCCC604HSGA TA3R 609 UGGGCGGGCUGAUGAGXCGAAAGGUGAAG2210CTTCACCTTCCCGCCCA514 515GUGGGCGGCUGAUGAGXCGAAAAGGUGAA2211TTCACCTTCCCGCCCAC610HSGA TA3R 634 HSGATA3R 516 XCGAAACUGCCUU2212AAGGACGTCTCCCCGGACUGAUGAG 517GGUCCGGGCUGAUGAGXCGAAAGACGUCC2213GGACGTCTCCCCGGACC636HSGA TA3R 518UGGACAGCCUGAUGAGXCGAAAUGGGUCC2214GGACCCATCGCTGTCCA648HSGA TA3R 654 HSGATA3R 519 CUGGGGUG CUGAUGAG X CGAA ACAGCGAU 2215 ATCGCTGT C CACCCCAG 520AGCCGGCCCUGAUGAGXCGAAAGCCUGGG2216CCCAGGCTCGGCCGGCT666HSGA TA3R 521GCCGGGCCCUGAUGAGXCGAAAGCCGGCC2217GGCCGGCTCGGCCCGGC675HSGA TA3R 522UGGUACUUCUGAUGAGXCGAAAGGCACUC2218GAGTGCCTCAAGTACCA703HSGA TA3R 523GCACCUGGCUGAUGAGXCGAAACUUGAGG2219CCTCAAGTACCTGGTGC708HSGA TA3R 524AGUGGGACCUGAUGAGXCGAAACUCCAGC2220GCTGGAGTCGTCCCACT744HSGA TA3R 747 GGGAGUGGCUGAUGAGXCGAAACGACUCC2221GGAGTCGTCCCACTCCC525 526UGCCACGGCUGAUGAGXCGAAAGUGGGAC2222GTCCCACTCCCGTGGCA753HSGA TA3R Table III. Hammerhead ribozymes targeting GATA transcription factors (1,'1, 3, 4, and 6) and the complementary sequences 786 UCGACGAGGUGAUGAGXCGAAAGGCUCCA2223TGGAGCCTCCTCGTCGA527 528GGGUCGACGUGAUGAGXCGAAAGGAGGCU2224AGCCTCCTCGTCGACCC789HSGA TA3R 529GGUGGGUCGUGAUGAGXCGAAACGAGGAG2225CTCCTCGTCGACCCACC798HSGA TA3R 530UAGGUGGUGUGAUGAGXCGAAAUGGGGUG2226CACCCCATCACCACCTA808HSGA TA3R 531AGGGCGGGGUGAUGAGXCGAAAGGUGGUG2227CACCACCTACCCGCCCT816HSGA TA3R 532CGGGCACGGUGAUGAGXCGAAAGGGCGGG2228CCCGCCCTACGTGCCCG825HSGA TA3R 533CGGAGCUGGUGAUGAGXCGAAACUCGGGC2229GCCCGAGTACAGCTCCG837HSGA TA3R 534AGAGUCCGGUGAUGAGXCGAAAGCUGUAC2230GTACAGCTCCGGACTCT843HSGA TA3R 535GGGGGGAAGUGAUGAGXCGAAAGUCCGGA2231TCCGGACTCTTCCCCCC850HSGA TA3R 536UGGGGGGGGUGAUGAGXCGAAAGAGUCCG2232CGGACTCTTCCCCCCCA852HSGA TA3R 853 CUGGGGGGGUGAUGAGXCGAAAAGAGUCC2233GGACTCTTCCCCCCCAG537 879 HSGATA3R 538 CGGUGGGG GUGAUGAG X CGAA AGCCGCCC 2234 GGGCGGCT C CCCCACCG 891 HSGATA3R 539 UGCAUCCG GUGAUGAG X CGAA AGCCGGUG 2235 CACCGGCT T CGGATGCA 892 HSGATA3R 540 UUGCAUCC GUGAUGAG X CGAA AAGCCGGU 2236 ACCGGCTT C GGATGCAA 903 HSGATA3R 541 UGGGCCUG GUGAUGAG X CGAA ACUUGCAU 2237 ATGCAAGT C CAGGCCCA 921 HSGATA3R 542 CUGUGCUG GUGAUGAG X CGAA ACCGGGCC 2238 GGCCCGGT C CAGCACAG 960 HSGATA3R 543 GUGGGGUC GUGAUGAG X CGAA AGGUUGCC 2239 GGCAACCT C GACCCCAC 996 HSGATA3R 544 UGCACAGG GUGAUGAG X CGAA AGUGUCCC 2240 GGGACACT A CCTGTGCA 1018 HSGATA3R 545 UUGUGAUA GUGAUGAG X CGAA AGCCCGCA 2241 TGCGGGCT C TATCACAA 1020 HSGATA3R 546 UUUUGUGA GUGAUGAG X CGAA AGAGCCCG 2242 CGGGCTCT A TCACAAAA 1022 HSGATA3R 547 CAUUUUGU GUGAUGAG X CGAA AUAGAGCC 2243 GGCTCTAT C ACAAAATG 1051 HSGATA3R 548 GGCUUAAU GUGAUGAG X CGAA AGGGGCCG 2244 CGGCCCCT C ATTAAGCC 1054 HSGATA3R 549 UUGGGCUU GUGAUGAG X CGAA AUGAGGGG 2245 CCCCTCAT T AAGCCCAA 1055 HSGATA3R 550 CUUGGGCU GUGAUGAG X CGAA AAUGAGGG 2246 CCCTCATT A AGCCCAAG 1074 HSGATA3R 551 UGGCUGCA GUGAUGAG X CGAA ACAGCCUU 2247 AAGGCTGT C TGCAGCCA 1098 HSGATA3R 552 UCGCACAG GUGAUGAG X CGAA ACGUCCCU 2248 AGGGACGT C CTGTGCGA 1112 HSGATA3R 553 GGUGGUCU GUGAUGAG X CGAA ACAGUUCG 2249 CGAACTGT C AGACCACC 1132 HSGATA3R 554 CUCCUCCA GUGAUGAG X CGAA AGUGUGGU 2250 ACCACACT C TGGAGGAG 1162 HSGATA3R 555 GCAUUGCA GUGAUGAG X CGAA ACAGGGUC 2251 GACCCTGT C TGCAATGC 556UUGUAGUAGUGAUGAGXCGAAAGCCCACA2252TGTGGGCTCTACTACAA1180HSG ATA3R 557GCUUGUAGGUGAUGAGXCGAAAGAGCCCA2253TGGGCTCTACTACAAGC1182HSG ATA3R 558GAAGCUUGGUGAUGAGXCGAAAGUAGAGC2254GCTCTACTACAAGCTTC1185HSG ATA3R 559AUGUUGUGGUGAUGAGXCGAAAGCUUGUA2255TACAAGCTTCACAATAT1192HSG ATA3R 560AAUAUUGUGUGAUGAGXCGAAAAGCUUGU2256ACAAGCTTCACAATATT1193HSG ATA3R 561UCUGUUAAGUGAUGAGXCGAAAUUGUGAA2257TTCACAATATTAACAGA1199HSG ATA3R 562GGUCUGUUGUGAUGAGXCGAAAUAUUGUG2258CACAATATTAACAGACC1201HSG ATA3R 563GGGUCUGUGUGAUGAGXCGAAAAUAUUGU2259ACAATATTAACAGACCC1202HSG ATA3R 564CUUCUUCAGUGAUGAGXCGAAAGUCAGGG2260CCCTGACTATGAAGAAG1217HSG ATA3R 1234 HSGATA3R 565 CUGGUCUG GUGAUGAG X CGAA AUGCCUUC 2261 GAAGGCAT C CAGACCAG 1257 HSGATA3R 566 AUUUGCUA GUGAUGAG X CGAA ACAUUUUU 2262 AAAAATGT C TAGCAAAT 1259 HSGATA3R 567 GGAUUUGC GUGAUGAG X CGAA AGACAUUU 2263 AAATGTCT A GCAAATCC 1266 HSGATA3R 568 ACUUUUUG GUGAUGAG X CGAA AUUUGCUA 2264 TAGCAAAT C CAAAAAGT 1293 HSGATA3R 569 CCUCCAGU GUGAUGAG X CGAA AGUCAUGC 2265 GCATGACT C ACTGGAGG 1305 HSGATA3R 570 UCUUGGGG GUGAUGAG X CGAA AGUCCUCC 2266 GGAGGACT T CCCCAAGA Table m. Hammerhead ribozymes targeting GATA transcription factors (1,2,3.4, and 6) and the complementary sequences 571UUCUUGGGCUGAUGAGXCGAAAAGUCCUC2267GAGGACTTCCCCAAGAA1306HSG ATA3R 572GGUUAAACCUGAUGAGXCGAAAGCUGUUC2268GAACAGCTCGTTTAACC1320HSG ATA3R 573CCGGGUUACUGAUGAGXCGAAACGAGCUG2269CAGCTCGTTTAACCCGG1323HSG ATA3R 574GCCGGGUUCUGAUGAGXCGAAAACGAGCU2270AGCTCGTTTAACCCGGC1324HSG ATA3R 1325 GGCCGGGUCUGAUGAGXCGAAAAACGAGC2271GCTCGTTTAACCCGGCC575 576UGUCUGGACUGAUGAGXCGAAAGGGCGGC2272GCCGCCCTCTCCAGACA1339HSG ATA3R 1341 UGUGUCUGCUGAUGAGXCGAAAGAGGGCG2273CGCCCTCTCCAGACACA577 578UCAGGGAGCUGAUGAGXCGAAACAUGUGU2274ACACATGTCCTCCCTGA1353HSG ATA3R 579GGCUCAGGCUGAUGAGXCGAAAGGACAUG2275CATGTOCTCCCTGAGCC1356HSG ATA3R 1369 HSGATA3R 580 AAGGGCGA CUGAUGAG X CGAA AUGUGGCU 2276 AGCCACAT C TCGCCCTT 581UGAAGGGCCUGAUGAGXCGAAAGAUGUGG2277CCACATCTCGCCCTTCA1371HSG ATA3R 1377 HSGATA3R 582 AGUGGCUG CUGAUGAG X CGAA AGGGCGAG 2278 CTCGCCCT T CAGCCACT 1378 HSGATA3R 583 GAGUGGCU CUGAUGAG X CGAA AAGGGCGA 2279 TCGCCCTT C AGCCACTC 1386 HSGATA3R 584 UGUGGCUG CUGAUGAG X CGAA AGUGGCUG 2280 CAGCCACT C CAGCCACA 1428 HSGATA3R 585 ACAGGCUG CUGAUGAG X CGAA AUGGCGGG 2281 CCCGCCAT C CAGCCTGT 1437 HSGATA3R 586 GUCCAAAG CUGAUGAG X CGAA ACAGGCUG 2282 CAGCCTGT C CTTTGGAC 1440 HSGATA3R 587 GUGGUCCA CUGAUGAG X CGAA AGGACAGG 2283 CCTGTCCT T TGGACCAC 1441 HSGATA3R 588 UGUGGUCC CUGAUGAG X CGAA AAGGACAG 2284 CTGTCCTT T GGACCACA 1458 HSGATA3R 589 CCAUGCUG CUGAUGAG X CGAA AGGGGUGG 2285 CCACCCCT C CAGCATGG 1468 HSGATA3R 590 AUGGCGGU CUGAUGAG X CGAA ACCAUGCU 2286 AGCATGGT C ACCGCCAT 1481 HSGATA3R 591 AGGGCUCU CUGAUGAG X CGAA ACCCAUGG 2287 CCATTGGT T AGAGCCCT 1482 HSGATA3R 592 CAGGGCUC CUGAUGAG X CGAA AACCCAUG 2288 CCTGGGTT A GAGCCCTG 1493 HSGATA3R 593 UGAGCAUC CUGAUGAG X CGAA AGCAGGGC 2289 GCCCTGCT C GATGCTCA 1500 HSGATA3R 594 GGCCCUGU CUGAUGAG X CGAA AGCAUCGA 2290 TCGATGCT C ACAGGGCC 1521 HSGATA3R 595 ACUGCAGG CUGAUGAG X CGAA ACUCUCGC 2291 GCGAGAGT C CCTGCAGT 1530 HSGATA3R 596 UCGAAAGG CUGAUGAG X CGAA ACUGCAGG 2292 CCTGCAGT C CCTTTCGA 1534 HSGATA3R 597 CAAGUCGA CUGAUGAG X CGAA AGGGACUG 2293 CAGTCCCT T TCGACTIC 1535 HSGATA3R 598 GCAAGUCG CUGAUGAG X CGAA AAGGGACU 2294 AGTCCCTT T CGACTIGC 1536 HSGATA3R 599 UGCAAGUC CUGAUGAG X CGAA AAAGGGAC 2295 GTCCCTTT C GACTTGCA 1541 HSGATA3R 600 AAAAAUGC CUGAUGAG X CGAA AGUCGAAA 2296 TTTCGACT T GCATTTTT 1546 HSGATA3R 601 CCUGCAAA CUGAUGAG X CGAA AUGCAAGU 2297 ACTTGCAT T TTTGCAGG 1547 HSGATA3R 602 UCCUGCAA CUGAUGAG X CGAA AAUGCAAG 2298 CTTGCATT T TTGCAGGA 1548 HSGATA3R 603 CUCCUGCA CUGAUGAG X CGAA AAAUGCAA 2299 TTGCATTT T TGCAGGAG 1549 HSGATA3R 604 GCUCCUGC CUGAUGAG X CGAA AAAAUGCA 2300 TGCATTTT T GCAGGAGC 1561 HSGATA3R 605 CUUCAUGA CUGAUGAG X CGAA ACUGCUCC 2301 GGAGCAGT A TCATGAAG 1563 HSGATA3R 606 GGCUUCAU CUGAUGAG X CGAA AUACUGCU 2302 AGCAGTAT C ATGAAGCC 1573 HSGATA3R 607 AUCGCGUU CUGAUGAG X CGAA AGGCUUCA 2303 TGAAGCCT A AACGCGAT 1586 HSGATA3R 608 AAAACAUA CUGAUGAG X CGAA AUCCAUCG 2304 CGATGGAT A TATGTTTT 1588 HSGATA3R 609 CAAAAACA CUGAUGAG X CGAA AUAUCCAU 2305 ATGGATAT A TGTTTTTG 1592 HSGATA3R 610 CCUUCAAA CUGAUGAG X CGAA ACAUAUAU 2306 ATATATGT T TTTGAAGG 1593 HSGATA3R 611 GCCUUCAA CUGAUGAG X CGAA AACAUAUA 2307 TATATGTT T TTGAAGGC 1594 HSGATA3R 612 UGCCUUCA CUGAUGAG X CGAA AAACAUAU 2308 ATATGTTT T TGAAGGCA 1595 HSGATA3R 613 CUGCCUUC CUGAUGAG X CGAA AAAACAUA 2309 TATGTTTT T GAAGGCAG 1614 HSGATA3R 614 GCAAACAU CUGAUGAG X CGAA AUUUUGCU 2310 AGCAAAAT T ATGTTTGC TablehoozymestargetingGAFAtranscriptionfactors(1,2,3,4,andHa nuneihead 6) and the complementary sequences 615GGCAAACACUGAUGAGXCGAAAAUUUUGC2311GCAAAATTATGTTTGCC1615HSG ATA3R 616AAGUGGCACUGAUGAGXCGAAACAUAAUU2312AATTATGTTTGCCACTT1619HSG ATA3R 617AAAGUGGCCUGAUGAGXCGAAAACAUAAU2313ATTATGTTTGCCACTTT1620HSG ATA3R 618CCUUUGCACUGAUGAGXCGAAAGUGGCAA2314TTGCCACTTTGCAAAGG1627HSG ATA3R 619UCCUUUGCCUGAUGAGXCGAAAAGUGGCA2315TGCCACTTTGCAAAGGA1628HSG ATA3R 620ACCACAGUCUGAUGAGXCGAAAGCUCCUU2316AAGGAGCTCACTGTGGT1640HSG ATA3R 621GGAACACACUGAUGAGXCGAAACACCACA2317TGTGGTGTCTGTGTTCC1651HSG ATA3R 622GUGGUUGGCUGAUGAGXCGAAACACAGAC2318GTCTGTGTTCCAACCAC1657HSG ATA3R 623AGUGGUUGCUGAUGAGXCGAAAACACAGA2319TCTGTGTTCCAACCACT1658HSG ATA3R 624GGGGUCCACUGAUGAGXCGAAAUUCAGUG2320CACTGAATCTGGACCCC1671HSG ATA3R 625UAUUCACACUGAUGAGXCGAAAUGGGGUC2321CACCCCATCTGTGAATA1682HSG ATA3R 626GAAUGGCUCUGAUGAGXCGAAAUUCACAG2322CTGTGAATAAGCCATTC1690HSG ATA3R 627UGAGUCAGCUGAUGAGXCGAAAUGGCUUA2323TAAGCCATTCTGACTCA1697HSG ATA3R 1698 HSGATA3R 628 AUGAGUCA CUGAUGAG X CGAA AAUGGCUU 2324 AAGCCATT C TGACTCAT 1704 HSGATA3R 629 GGGGAUAU CUGAUGAG X CGAA AGUCAGAA 2325 TTCTGACT C ATATCCCC 1707 HSGATA3R 630 AUAGGGGA CUGAUGAG X CGAA AUGAGUCA 2326 TGACTCAT A TCCCCTAT 1709 HSGATA3R 631 AAAUAGGG CUGAUGAG X CGAA AUAUGAGU 2327 ACTCATAT C CCCTATTT 1714 HSGATA3R 632 CUGUUAAA CUGAUGAG X CGAA AGGGGAUA 2328 TATCCCCT A TTTAACAG 633CCCUGUUACUGAUGAGXCGAAAUAGGGGA2329TCCCCTATTTAACAGGG1716HSG ATA3R 634ACCCUGUUCUGAUGAGXCGAAAAUAGGGG2330CCCCTATTTAACAGGGT1717HSG ATA3R 1718 HSGATA3R 635 GACCCUGU CUGAUGAG X CGAA AAAUAGGG 2331 CCCTATTT A ACAGGGTC 1726 HSGATA3R 636 GCACUAGA CUGAUGAG X CGAA ACCCUGUU 2332 AACAGGGT C TCTAGTGC 1728 HSGATA3R 637 CAGCACUA CUGAUGAG X CGAA AGACCCUG 2333 CAGGGTCT C TAGTGCTG 1730 HSGATA3R 638 CACAGCAC CUGAUGAG X CGAA AGAGACCC 2334 GGGTCTCT A GTGCTGTG 1751 HSGATA3R 639 AUGUUCAG CUGAUGAG X CGAA AUUUUUUU 2335 AAAAAAAT C CTGAACAT 1760 HSGATA3R 640 UUAUAUGC CUGAUGAG X CGAA AUGUUCAG 2336 CTGAACAT T GCATATAA 1765 HSGATA3R 641 AUAAGUUA CUGAUGAG X CGAA AUGCAAUG 2337 CATTGCAT A TAACTTAT 1767 HSGATA3R 642 AUAUAAGU CUGAUGAG X CGAA AUAUGCAA 2338 TTGCATAT A ACTTATAT 1771 HSGATA3R 643 UACAAUAU CUGAUGAG X CGAA AGUUAUAU 2339 ATATAACT T ATATTGTA 1772 HSGATA3R 644 UUACAAUA CUGAUGAG X CGAA AAGUUAUA 2340 TATAACTT A TATTGTAA 1774 HSGATA3R 645 UCUUACAA CUGAUGAG X CGAA AUAAGUUA 2341 TAACTTAT A TTGTAAGA 1776 HSGATA3R 646 UUUCUUAC CUGAUGAG X CGAA AUAUAAGU 2342 ACTTATAT T GTAAGAAA 1779 HSGATA3R 647 GUAUUUCU CUGAUGAG X CGAA ACAAUAUA 2343 TATATTGT A AGAAATAC 1786 HSGATA3R 648 UUGUACAG CUGAUGAG X CGAA AUUUCUUA 2344 TAAGAAAT A CTGTACAA 1791 HSGATA3R 649 AGUCAUUG CUGAUGAG X CGAA ACAGUAUU 2345 AATACTGT A CAATGACT 1800 HSGATA3R 650 AUGCAAUA CUGAUGAG X CGAA AGUCAUUG 2346 CAATGACT T TATTGCAT 1801 HSGATA3R 651 GAUGCAAU CUGAUGAG X CGAA AAGUCAUU 2347 AATGACTT T ATTGCATC 1802 HSGATA3R 652 AGAUGCAA CUGAUGAG X CGAA AAAGUCAU 2348 ATGACTTT A TTGCATCT 1804 HSGATA3R 653 CCAGAUGC CUGAUGAG X CGAA AUAAAGUC 2349 GACTTTAT T GCATCTGG 1809 HSGATA3R 654 GCUACCCA CUGAUGAG X CGAA AUGCAAUA 2350 TATTGCAT C TGGGTAGC 1815 HSGATA3R 655 CUUACAGC CUGAUGAG X CGAA ACCCAGAU 2351 ATCTGGGT A GCTGTAAG 1821 HSGATA3R 656 UCAUGCCU CUGAUGAG X CGAA ACAGCUAC 2352 GTAGCTGT A AGGCATGA 1845 HSGATA3R 657 AUUCCUUA CUGAUGAG X CGAA ACUUCUUG 2353 CAAGAAGT T TAAGGAAT 1846 HSGATA3R 658 UAUUCCUU CUGAUGAG X CGAA AACUUCUU 2354 AAGAAGTT T AAGGAATA Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1847 HSGATA3R 659 XCGAAAAACUUCU2355AGAAGTTTAAGGAATATCUGAUGAG 660UUCUCCCACUGAUGAGXCGAAAUUCCUUA2356TAAGGAATATGGGAGAA1854HSG ATA3R 661UUCCACACCUGAUGAGXCGAAAUUUCUCC2357GGAGAAATAGTGTGGAA1865HSG ATA3R 662UUCUUCUUCUGAUGAGXCGAAAUUUCCAC2358GTGGAAATTAAGAAGAA1876HSG ATA3R 663UUUCUUCUCUGAUGAGXCGAAAAUUUCCA2359TGGAAATTAAGAAGAAA1877HSG ATA3R 664AUCAGACCCUGAUGAGXCGAAAGUUUCUU2360AAGAAACTAGGTCTGAT1888HSG ATA3R 665GAAUAUCACUGAUGAGXCGAAACCUAGUU2361AACTAGGTCTGATATTC1892HSG ATA3R 666CAUUUGAACUGAUGAGXCGAAAUCAGACC2362GGTCTGATATTCAAATG1897HSG ATA3R 667UCCAUUUGCUGAUGAGXCGAAAUAUCAGA2363TCTGATATTCAAATGGA1899HSG ATA3R 668GUCCAUUUCUGAUGAGXCGAAAAUAUCAG2364CTGATATTCAAATGGAC1900HSG ATA3R 669GGAAACAACUGAUGAGXCGAAACUGGCAG2365CTGCCAGTTTTGTTTCC1920HSG ATA3R 670AGGAAACACUGAUGAGXCGAAAACUGGCA2366TGCCAGTTTTGTTTCCT1921HSG ATA3R 671AAGGAAACCUGAUGAGXCGAAAAACUGGC2367GCCAGTTTTGTTTCCTT1922HSG ATA3R 672UGAAAGGACUGAUGAGXCGAAACAAAACU2368AGTTTTGTTTCCTTTCA1925HSG ATA3R 673GUGAAAGGCUGAUGAGXCGAAAACAAAAC2369GTTTTGTTTCCTTTCAC1926HSG ATA3R 1927 HSGATA3R 674 AGUGAAAG CUGAUGAG X CGAA AAACAAAA 2370 TTTTGTTT C CTTTCACT 1930 HSGATA3R 675 GCCAGUGA CUGAUGAG X CGAA AGGAAACA 2371 TGTTTCCT T TCACTGGC 1931 H9GATA3R 676 GGCCAGUG CUGAUGAG X CGAA AAGGAAAC 2372 GTTTCCTT T OC= 1932 HSGATA3R 677 UGGCCAGU CUGAUGAG X CGAA AAAGGAAA 2373 TTTCCTTT C ACTGGCCA 1945 HSGATA3R 678 CAUCAAAC CUGAUGAG X CGAA ACUGUGGC 2374 GC=WuT T arrimm 1948 HSGATA3R 679 AUGCAUCA CUGAUGAG X CGAA ACAACUGU 2375 ACAGTTGT T TGATGCAT 1949 HSGATA3R 680 AAUGCAUC CUGAUGAG X CGAA AACAACUG 2376 CAGTTGTT T GATGCATT 1957 HSGATA3R 681 UUUCUUUU CUGAUGAG X CGAA AUGCAUCA 2377 TCA7= T AAAAGAAA 1958 HSGATA3R 682 UUUUCUUU CUGAUGAG X CGAA AAUGCAUC 2378 GATGCATT A AAAGAAAA 1968 ESTA3R 683 CUUUUUUU CUGAUGAG X CGAA AUUUUCUU 2379 APAAT A AAAAAAPG 1957 HSGATA3R 681 UUUCUUUU CUGAUGAG X CGAA AUGCAUCA 2377 TGATGCAT T AAAAGAAA 1958 HSGATA3R 682 UUUUCUUU CUGAUGAG X CGAA AAUGCAUC 2378 GATGCATT A AAAGAAAA 1968 HSGATA3R 683 CUUUUUUU CUGAUGAG X CGAA AUUUUCUU 2379 AAGAAAAT A AAAAAAAG 2009 HSGATA3R 684 UCGCCUAC CUGAUGAG X CGAA ACUUUUUU 2380 AAAAAAGT T GTAGGCGA 2012 HSGATA3R 685 GAUUCGCC CUGAUGAG X CGAA ACAACUUU 2381 AAAGTTGT A GGCGAATC 2020 HSGATA3R 686 GAACAAAU CUGAUGAG X CGAA AUUCGCCU 2382 AGGCGAAT C ATTTGTTC 2023 HSGATA3R 687 UUUGAACA CUGAUGAG X CGAA AUGAUUCG 2383 CGAATCAT T TGTTCAAA 2024 HSGATA3R 688 CUUUGAAC CUGAUGAG X CGAA AAUGAUUC 2384 GAATCATT T GTTCAAAG 2027 HSGATA3R 689 CAGCUUUG CUGAUGAG X CGAA ACAAAUGA 2385 TCATTTGT T CAAAGCTG 2028 HSGATA3R 690 ACAGCUUU CUGAUGAG X CGAA AACAAAUG 2386 CATTTGTT C AAAGCTGT 2037 HSGATA3R 691 AGAGGGCC CUGAUGAG X CGAA ACAGCUUU 2387 AAAGCTGT T GGCCCTCT 2044 HSGATA3R 692 CCUUUGCA CUGAUGAG X CGAA AGGGCCAA 2388 TTGGCCCT C TGCAAAGG 2057 HSGATA3R 693 AGAACUGG CUGAUGAG X CGAA AUUUCCUU 2389 AAGGAAAT A CCAGTTCT 2063 HSGATA3R 694 UUGCCCAG CUGAUGAG X CGAA ACUGGUAU 2390 ATACCAGT T CTGGGCAA 2064 HSGATA3R 695 AUUGCCCA CUGAUGAG X CGAA AACUGGUA 2391 TACCAGTT C TGGGCAAT 2073 HSGATA3R 696 GUAACACU CUGAUGAG X CGAA AUUGCCCA 2392 TGGGCAAT C AGTGTTAC 2079 HSGATA3R 697 UGAACGGU CUGAUGAG X CGAA ACACUGAU 2393 ATCAGTGT T ACCGTTCA 2080 HSGATA3R 698 GUGAACGG CUGAUGAG X CGAA AACACUGA 2394 TCAGTGTT A CCGTTCAC 2085 HSGATA3R 699 AACUGGUG CUGAUGAG X CGAA ACGGUAAC 2395 GTTACCGT T CACCAGTT 2086 HSGATA3R 700 CAACUGGU CUGAUGAG X CGAA AACGGUAA 2396 TTACCGTT C ACCAGTTG 2093 HSGATA3R 701 UCAAUGGC CUGAUGAG X CGAA ACUGGUGA 2397 TCACCAGT T GCCATTGA 2099 HSGATA3R 702 AAACCCUC CUGAUGAG X CGAA AUGGCAAC 2398 GTTGCCAT T GAGGGTTT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 703CUCUCUGACUGAUGAGXCGAAACCCUCAA2399TTGAGGGTTTCAGAGAG2106HSG ATA3R 704GCUCUCUGCUGAUGAGXCGAAAACCCUCA2400TGAGGGTTTCAGAGAGC2107HSG ATA3R 705GGCUCUCUCUGAUGAGXCGAAAAACCCUC2401GAGGGTTTCAGAGAGCC2108HSG ATA3R 706CCUAGAAACUGAUGAGXCGAAAGGCUCUC2402GAGAGCCTTTTTCTAGG2118HSG ATA3R 707GCCUAGAACUGAUGAGXCGAAAAGGCUCU2403AGAGCCTTTTTCTAGGC2119HSG ATA3R 708GGCCUAGACUGAUGAGXCGAAAAAGGCUC2404GAGCCTTTTTCTAGGCC2120HSG ATA3R 2121 AGGCCUAGCUGAUGAGXCGAAAAAAGGCU2405AGCCTTTTTCTAGGCCT709 710UAGGCCUACUGAUGAGXCGAAAAAAAGGC2406GCCTTTTTCTAGGCCTA2122HSG ATA3R 711UGUAGGCCCUGAUGAGXCGAAAGAAAAAG2407CTTTTTCTAGGCCTACA2124HSG ATA3R 712AAAGCAUGCUGAUGAGXCGAAAGGCCUAG2408CTAGGCCTACATGCTTT2130HSG ATA3R 713UGUUCACACUGAUGAGXCGAAAGCAUGUA2409TACATGCTATGTGAACA2137HSG ATA3R 714UUGUUCACCUGAUGAGXCGAAAAGCAUGU2410ACATGCTTTGTGAACAA2138HSG ATA3R 715AUUACAGGCUGAUGAGXCGAAACUUGUUC2411GAACAAGTCCCTGTAAT2149HSG ATA3R 716ACAACAAUCUGAUGAGXCGAAACAGGGAC2412GTCCCTGTAATTGTTGT2155HSG ATA3R 2158 HSGATA3R 717 CAAACAAC CUGAUGAG X CGAA AUUACAGG 2413 CCTGTAAT T GTTGTTTG 718AUACAAACCUGAUGAGXCGAAACAAUUAC2414GTAATTGTTGTTTGTAT2161HSG ATA3R 719UACAUACACUGAUGAGXCGAAACAACAAU2415ATTGTTGTTTGTATGTA2164HSG ATA3R 2165 HSGATA3R 720 AUACAUAC CUGAUGAG X CGAA AACAACAA 2416 TTGTTGTT T GTATGTAT 721AUUAUACACUGAUGAGXCGAAACAAACAA2417TTGTTTGTATGTATAAT2168HSG ATA3R 2172 HSGATA3R 722 UUGAAUUA CUGAUGAG X CGAA ACAUACAA 2418 TTGTATGT A TAATTCAA 2174 HSGATA3R 723 CUUUGAAU CUGAUGAG X CGAA AUACAUAC 2419 GTATGTAT A ATTCAAAG 2177 HSGATA3R 724 GUGCUUUG CUGAUGAG X CGAA AUUAUACA 2420 TGTATAAT T CAAAGCAC 2178 HSGATA3R 725 GGUGCUUU CUGAUGAG X CGAA AAUUAUAC 2421 GTATAATT C AAAGCACC 2192 HSGATA3R 726 UCUUUUCU CUGAUGAG X CGAA AUUUUGGU 2422 ACCAAAAT A AGAAAAGA 2204 HSGATA3R 727 AAUAAAUC CUGAUGAG X CGAA ACAUCUUU 2423 AAAGATGT A GATTTATT 2208 HSGATA3R 728 AUGAAAUA CUGAUGAG X CGAA AUCUACAU 2424 ATGTAGAT T TATTTCAT 2209 HSGATA3R 729 GAUGAAAU CUGAUGAG X CGAA AAUCUACA 2425 TGTAGATT T ATTTCATC 2210 HSGATA3R 730 UGAUGAAA CUGAUGAG X CGAA AAAUCUAC 2426 GTAGATTT A TTTCATCA 2212 HSGATA3R 731 UAUGAUGA CUGAUGAG X CGAA AUAAAUCU 2427 AGATTTAT T TCATCATA 2213 HSGATA3R 732 AUAUGAUG CUGAUGAG X CGAA AAUAAAUC 2428 GATTTATT T CATCATAT 2214 HSGATA3R 733 AAUAUGAU CUGAUGAG X CGAA AAAUAAAU 2429 ATTTATTT C ATCATATT 2217 HSGATA3R 734 UAUAAUAU CUGAUGAG X CGAA AUGAAAUA 2430 TATTTCAT C ATATTATA 2220 HSGATA3R 735 CUGUAUAA CUGAUGAG X CGAA AUGAUGAA 2431 TTCATCAT A TTATACAG 2222 HSGATA3R 736 GUCUGUAU CUGAUGAG X CGAA AUAUGAUG 2432 CATCATAT T ATACAGAC 2223 HSGATA3R 737 GGUCUGUA CUGAUGAG X CGAA AAUAUGAU 2433 ATCATATT A TACAGACC 2225 HSGATA3R 738 UCGGUCUG CUGAUGAG X CGAA AUAAUAUG 2434 CATATTAT A CAGACCGA 2239 HSGATA3R 739 AUUUAUAC CUGAUGAG X CGAA ACAGUUCG 2435 CGAACTGT T GTATAAAT 2242 HSGATA3R 740 UAAAUUUA CUGAUGAG X CGAA ACAACAGU 2436 ACTGTTGT A TAAATTTA 2244 HSGATA3R 741 AAUAAAUU CUGAUGAG X CGAA AUACAACA 2437 TGTTGTAT A AATTTATT 2248 HSGATA3R 742 AGUAAAUA CUGAUGAG X CGAA AUUUAUAC 2438 GTATAAAT T TATTTACT 2249 HSGATA3R 743 CAGUAAAU CUGAUGAG X CGAA AAUUUAUA 2439 TATAAATT T ATTTACTG 2250 HSGATA3R 744 GCAGUAAA CUGAUGAG X CGAA AAAUUUAU 2440 ATAAATTT A TTTACTGC 2252 HSGATA3R 745 UAGCAGUA CUGAUGAG X CGAA AUAAAUUU 2441 AAATTTAT T TACTGCTA 2253 HSGATA3R 746 CUAGCAGU CUGAUGAG X CGAA AAUAAAUU 2442 AATTTATT T ACTGCTAG Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 747ACUAGCAGCUGAUGAGXCGAAAAAUAAAU2443ATTTATTTACTGCTAGT2254HSG ATA3R 748CUUAAGACCUGAUGAGXCGAAAGCAGUAA2444TTACTGCTAGTCTTAAG2260HSG ATA3R 749GUUCUUAACUGAUGAGXCGAAACUAGCAG2445CTGCTAGTCTTAAGAAC2263HSG ATA3R 750CAGUUCUUCUGAUGAGXCGAAAGACUAGC2446GCTAGTCTTAAGAACTG2265HSG ATA3R 751GCAGUUCUCUGAUGAGXCGAAAAGACUAG2447CTAGTCTTAAGAACTGC2266HSG ATA3R 752ACGAAAGACUGAUGAGXCGAAAGCAGUUC2448GAACTGCTTTCTTTCGT2276HSG ATA3R 753AACGAAAGCUGAUGAGXCGAAAAGCAGUU2449AACTGCTTTCTTTCGTT2277HSG ATA3R 754AAACGAAACUGAUGAGXCGAAAAAGCAGU2450ACTGCTTTCTTTCGTTT2278HSG ATA3R 755ACAAACGACUGAUGAGXCGAAAGAAAGCA2451TGCTTTCTTTCGTTTGT2280HSG ATA3R 756AACAAACGCUGAUGAGXCGAAAAGAAAGC2452GCTTTCTTTCGTTTGTT2281HSG ATA3R 757AAACAAACCUGAUGAGXCGAAAAAGAAAG2453CTTTCTTTCGTTTGTTT2282HSG ATA3R 758AACAAACACUGAUGAGXCGAAACGAAAGA2454TCTTTCGTTTGTTTGTT2285HSG ATA3R 759AAACAAACCUGAUGAGXCGAAAACGAAAG2455CTTTCGTTTGTTTGTTT2286HSG ATA3R 760UUGAAACACUGAUGAGXCGAAACAAACGA2456TCGTTTGTTTGTTTCAA2289HSG ATA3R 761AUUGAAACCUGAUGAGXCGAAAACAAACG2457CGTTTGTTTGTTTCAAT2290HSG ATA3R 762AAUAUUGACUGAUGAGXCGAAACAAACAA2458TTGTTTGTTTCAATATT2293HSG ATA3R 763AAAUAUUGCUGAUGAGXCGAAAACAAACA2459TGTTTGTTTCAATATTT2294HSG ATA3R 764AAAAUAUUCUGAUGAGXCGAAAAACAAAC2460GTTTGTTTCAATATTTT2295HSG ATA3R 765AAGGAAAACUGAUGAGXCGAAAUUGAAAC2461GTTTCAATATTTTCCTT2299HSG ATA3R 766AGAAGGAACUGAUGAGXCGAAAUAUUGAA2462TTCAATATTTTCCTTCT2301HSG ATA3R 767GAGAAGGACUGAUGAGXCGAAAAUAUUGA2463TCAATATTTTCCTTCTC2302HSG ATA3R 768AGAGAAGGCUGAUGAGXCGAAAAAUAUUG2464CAATATTTTCCTTCTCT2303HSG ATA3R 769GAGAGAAGCUGAUGAGXCGAAAAAAUAUU2465AATATTTTCCTTCTCTC2304HSG ATA3R 770UGAGAGAGCUGAUGAGXCGAAAGGAAAAU2466ATTTTCCTTCTCTCTCA2307HSG ATA3R 771UUGAGAGACUGAUGAGXCGAAAAGGAAAA2467TTTTCCTTCTCTCTCAA2308HSG ATA3R 772AAUUGAGACUGAUGAGXCGAAAGAAGGAA2468TTCCTTCTCTCTCAATT2310HSG ATA3R 773AAAAUUGACUGAUGAGXCGAAAGAGAAGG2469CCTTCTCTCTCAATTTT2312HSG ATA3R 774CGAAAAUUCUGAUGAGXCGAAAGAGAGAA2470TTCTCTCTCAATTTTCG2314HSG ATA3R 775CAACCGAACUGAUGAGXCGAAAUUGAGAG2471CTCTCAATTTTCGGTTG2318HSG ATA3R 776UCAACCGACUGAUGAGXCGAAAAUUGAGA2472TCTCAATTTTCGGTTGA2319HSG ATA3R 2320 UUCAACCGCUGAUGAGXCGAAAAAUUGAG2473CTCAATTTTCGGTTGAA777 778AUUCAACCCUGAUGAGXCGAAAAAAUUGA2474TCAATTTTCGGTTGAAT2321HSG ATA3R 779GUUUAUUCCUGAUGAGXCGAAACCGAAAA2475TTTTCGGTTGAATAAAC2325HSG ATA3R 780AUCUAGUUCUGAUGAGXCGAAAUUCAACC2476GGTTGAATAAACTAGAT2330HSG ATA3R 781AUGUAAUCCUGAUGAGXCGAAAGUUUAUU2477AATAAACTAGATTACAT2335HSG ATA3R 2339 CUGAAUGACUGAUGAGXCGAAAUCUAGUU2478AACTAGATTACATTCAG782 783ACUGAAUGCUGAUGAGXCGAAAAUCUAGU2479ACTAGATTACATTCAGT2340HSG ATA3R 2344 HSGATA3R 784 GCCAACUG CUGAUGAG X CGAA AUGUAAUC 2480 GATTACAT T CAGTTGGC 785UGCCAACUCUGAUGAGXCGAAAAUGUAAU2481ATTACATTCAGTTGGCA2345HSG ATA3R 786UUUUUGCCCUGAUGAGXCGAAACUGAAUG2482CATTCAGTTGGCAAAAA2349HSG ATA3R 13 CCAAUUUGCUGAUGAGXCGAAAUUUUUGG2483CCAAAAATTCAAATTGG787 788CCCAAUUUCUGAUGAGXCGAAAAUUUUUG2484CAAAAATTTAAATTGGG14HUMGA TAA 19 AAAAUCCCCUGAUGAGXCGAAAUUUGAAU2485ATTCAAATTGGGATTTT789 790CUCCGGAACUGAUGAGXCGAAAUCCCAAU2486ATTGGGATTTTCCGGAG25HUMGA TAA Table III. Hammerhead ribozymes targeting GATA transcription factors (L, and 6) and the complementary sequences 791ACUCCGGACUGAUGAGXCGAAAAUCCCAA2487TTGGGATTTTCCGGAGT26HUMGA TAA 792UACUCCGGCUGAUGAGXCGAAAAAUCCCA2488TGGGATTTTCCGGAGTA27HUMGA TAA 793UUACUCCGCUGAUGAGXCGAAAAAAUCCC2489GGGATTTTTCGGAGTAA28HUMGA TAA 35 CUCUUGUUCUGAUGAGXCGAAACUCCGGA2490TCCGGAGTAAACAAGAG794 795AAGGGCUCCUGAUGAGXCGAAAGGCUCUU2491AAGAGCCTAGAGCCCTT47HUMGA TAA 55 AUUGAGCACUGAUGAGXCGAAAGGGCUCU2492AGAGCCCTTTGCTCAAT796 797CAUUGAGCCUGAUGAGXCGAAAAGGGCUC2493GAGCCCTTTGCTCAATG56HUMGA TAA 798CCAGCAUUCUGAUGAGXCGAAAGCAAAGG2494CCTTTGCTCAATGCTGG60HUMGA TAA 71 HUMGATAA 799 ACGUAUUA CUGAUGAG X CGAA AUCCAGCA 2495 TGCTGGAT T TAATACGT 72 HUMGATAA 800 UACGUAUU CUGAUGAG X CGAA AAUCCAGC 2496 GCTGGATT T AATACGTA 801AUACGUAUCUGAUGAGXCGAAAAAUCCAG2497CTGGATTTAATACGTAT73HUMGA TAA 802UAUAUACGCUGAUGAGXCGAAAUUAAAUC2498GATTTAATACGTATATA76HUMGA TAA 803AAAAUAUACUGAUGAGXCGAAACGUAUUA2499TAATACGTATATATTTT80HUMGA TAA 804UAAAAAUACUGAUGAGXCGAAAUACGUAU2500ATACGTATATATTTTTA82HUMGA TAA 84 CUUAAAAACUGAUGAGXCGAAAUAUACGU2501ACGTATATATTTTTAAG805 86 CGCUUAAACUGAUGAGXCGAAAUAUAUAC2502GTATATATATTTAAGCG806 807UCGCUUAACUGAUGAGXCGAAAAUAUAUA2503TATATATTTTTAAGCGA87HUMGA TAA 88 HUMGATAA 808 CUCGCUUA CUGAUGAG X CGAA AAAUAUAU 2504 ATATATTT T TAAGCGAG 89 HUMGATAA 809 ACUCGCUU CUGAUGAG X CGAA AAAAUAUA 2505 TATATTTT T AAGCGAGT 9090HUMGATAA 810 AACUCGCU CUGAUGAG X CGAA AAAAAUAU 2506 ATATTTTT A AGCGAGTT 98 HUMGATAA 811 AAAAAACC CUGAUGAG X CGAA ACUCGCUU 2507 AAGCGAGT T GGTTTTTT 102 HUMGATAA 812 GGGGAAAA CUGAUGAG X CGAA ACCAACUC 2508 GAGTTGGT T TTTTCCCC 103 AGGGGAAACUGAUGAGXCGAAAACCAACU2509AGTTGGTTTTTTCCCCT813 814AAGGGGAACUGAUGAGXCGAAAAACCAAC2510GTTGGTTTTTTCCCCTT104HUMG ATAA 105 AAAGGGGACUGAUGAGXCGAAAAAACCAA2511TTGGTTTTTTCCCCTTT815 106 HUMGATAA 816 CAAAGGGG CUGAUGAG X CGAA AAAAACCA 2512 TGGTTTTT T CCCCTTTG 107 HUMGATAA 817 UCAAAGGG CUGAUGAG X CGAA AAAAAACC 2513 GGTTTTTT C CCCTTTGA 112112HUMGATAA 818 AAAAAUCA CUGAUGAG X CGAA AGGGGAAA 2514 TTTCCCCT T TGATTTTT 113113HUMGATAA 819 CAAAAAUC CUGAUGAG X CGAA AAGGGGAA 2515 TTCCCCTT T GATTTTTG 117 HUMGATAA 820 AGAUCAAA CUGAUGAG X CGAA AUCAAAGG 2516 CCTTTGAT T TTTGATCT 118 HUMGATAA 821 AAGAUCAA CUGAUGAG X CGAA AAUCAAAG 2517 CTTTGATT T TTGATCTT 119119HUMGATAA 822 GAAGAUCA CUGAUGAG X CGAA AAAUCAAA 2518 TTTGATTT T TGATCTTC 120 HUMGATAA 823 CGAAGAUC CUGAUGAG X CGAA AAAAUCAA 2519 TTGATTTT T GATCTTCG 124 HUMGATAA 824 GUCGCGAA CUGAUGAG X CGAA AUCAAAAA 2520 TTTTTGAT C TTCGCGAC 126 HUMGATAA 825 CUGUCGCG CUGAUGAG X CGAA AGAUCAAA 2521 TTTGATCT T CGCGACAG 127 HUMGATAA 826 ACUGUCGC CUGAUGAG X CGAA AAGAUCAA 2522 TTGATCTT C GCGACAGT 136 HUMGATAA 827 GUGGGAGG CUGAUGAG X CGAA ACUGUCGC 2523 GCGACAGT T CCTCCCAC 137 HUMGATAA 828 CGUGGGAG CUGAUGAG X CGAA AACUGUCG 2524 CGACAGTT C CTCCCACG 140 HUMGATAA 829 AUGCGUGG CUGAUGAG X CGAA AGGAACUG 2525 CAGTTCCT C CCACGCAT 149 HUMGATAA 830 AACGAUAA CUGAUGAG X CGAA AUGCGUGG 2526 CCACGCAT A TTATCGTT 151 HUMGATAA 831 ACAACGAU CUGAUGAG X CGAA AUAUGCGU 2527 ACGCATAT T ATCGTTGT 152 HUMGATAA 832 AACAACGA CUGAUGAG X CGAA AAUAUGCG 2528 CGCATATT A TCGTTGTT 154 HUMGATAA 833 GCAACAAC CUGAUGAG X CGAA AUAAUAUG 2529 CATATTAT C GTTGTTGC 157 HUMGATAA 834 ACGGCAAC CUGAUGAG X CGAA ACGAUAAU 2530 ATTATCGT T GTTGCCGT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2.3,4, and 6) and the complementary sequences 835ACGACGGCCUGAUGAGXCGAAACAACGAU2531ATCGTTGTTGCCGTCGT160HUMG ATAA 836GAGAAAACCUGAUGAGXCGAAACGGCAAC2532GTTGCCGTCGTTTTCTC166HUMG ATAA 837GGAGAGAACUGAUGAGXCGAAACGACGGC2533GCCGTCGTTTTCTCTCC169HUMG ATAA 838GGGAGAGACUGAUGAGXCGAAAACGACGG2534CCGTCGTTTTCTCTCCC170HUMG ATAA 839GGGGAGAGCUGAUGAGXCGAAAAACGACG2535CGTCGTTTTCTCTCCCC171HUMG ATAA 840CGGGGAGACUGAUGAGXCGAAAAAACGAC2536GTCGTTTTCTCTCCCCG172HUMG ATAA 841CGCGGGGACUGAUGAGXCGAAAGAAAACG2537CGTTTTCTCTCCCCGCG174HUMG ATAA 842CACGCGGGCUGAUGAGXCGAAAGAGAAAA2538TTTTCTCTCCCCGCGTG176HUMG ATAA 843AGGUCAAGCUGAUGAGXCGAAAGCCACGC2539GCGTGGCTCCTTGACCT188HUMG ATAA 844CGCAGGUCCUGAUGAGXCGAAAGGAGCCA2540TGGCTCCTTGACCTGCG191HUMG ATAA 845GUCCCUGCCUGAUGAGXCGAAAGCUCCCG2541CGGGAGCTCGCAGGGAC231HUMG ATAA 846AGCUCUGACUGAUGAGXCGAAACAUGGUC2542GACCATGTATCAGAGCT245HUMG ATAA 847CAAGCUCUCUGAUGAGXCGAAAUACAUGG2543CCATGTATCAGAGCTTG247HUMG ATAA 848CCAUGGCCCUGAUGAGXCGAAAGCUCUGA2544TCAGAGCTTGGCCATGG254HUMG ATAA 849CCGCCUGGCUGAUGAGXCGAAAGGCACCG2545CGGTGCCTACCAGGCGG293HUMG ATAA 850CGUGCAUGCUGAUGAGXCGAAAGGGGCCG2546CGGCCCCTTCATGCACG317HUMG ATAA 851CCGUGCAUCUGAUGAGXCGAAAAGGGGCC2547GGCCCCTTCATGCACGG318HUMG ATAA 341 HUMGATAA 852 CUGGCGAG CUGAUGAG X CGAA ACGCGGCG 2548 CGCCGCGT C CTCGCCAG 344 HUMGATAA 853 AGACUGGC CUGAUGAG X CGAA AGGACGCG 2549 CGCGTCCT C GCCAGTCT 351 HUMGATAA 854 GGCAGGUA CUGAUGAG X CGAA ACUGGCGA 2550 TCGCCAGT C TACCTGCC 353 HUMGATAA 855 UGGGCAGG CUGAUGAG X CGAA AGACUGGC 2551 GCCAGTCT A CCTGCCCA 377 HUMGATAA 856 GAACGGAG CUGAUGAG X CGAA AGGGCACC 2552 GGTGCCCT C CTCCGTTC 380 HUMGATAA 857 CCAGAACG CUGAUGAG X CGAA AGGAGGGC 2553 GCCCTCCT C CGTTCTGG 858AGGCCCAGCUGAUGAGXCGAAACGGAGGA2554TCCTCCGTTCTGGGCCT384HUMG ATAA 385385HUMGATAA 859 CAGGCCCA CUGAUGAG X CGAA AACGGAGG 2555 CCTCCGTT C TGGGCCTG 395 HUMGATAA 860 GGAGGUAG CUGAUGAG X CGAA ACAGGCCC 2556 GGGCCTGT C CTACCTCC 398 HUMGATAA 861 CCUGGAGG CUGAUGAG X CGAA AGGACAGG 2557 CCTGTCCT A CCTCCAGG 402 HUMGATAA 862 CCGCCCUG CUGAUGAG X CGAA AGGUAGGA 2558 TCCTACCT C CAGGGCGG 422 HUMGATAA 863 CGGACGCA CUGAUGAG X CGAA AGCCCGCG 2559 CGCGGGCT C TGCGTCCG 428 HUMGATAA 864 GGCCUCCG CUGAUGAG X CGAA ACGCAGAG 2560 CTCTGCGT C CGGAGGCC 440 HUMGATAA 865 UGCCGCCC CUGAUGAG X CGAA AGGGGCCU 2561 AGGCCCCT C GGGCGGCA 467 HUMGATAA 866 CCGCACCA CUGAUGAG X CGAA ACGCGGCC 2562 GGCCGCGT C TGGTGCGG 535 HUMGATAA 867 CGGGGUGU CUGAUGAG X CGAA AGCGGCUC 2563 GAGCCGCT T ACACCCCG 536 HUMGATAA 868 GCGGGGUG CUGAUGAG X CGAA AAGCGGCU 2564 AGCCGCTT A CACCCCGC 554 HUMGATAA 869 AGCGCGGC CUGAUGAG X CGAA ACACCGGC 2565 GCCGGTGT C GCCGCGCT 563 HUMGATAA 870 GGAAGGAG CUGAUGAG X CGAA AGCGCGGC 2566 GCCGCGCT T CTCCTTCC 564 HUMGATAA 871 GGGAAGGA CUGAUGAG X CGAA AAGCGCGG 2567 CCGCGCTT C TCCTTCCC 566 HUMGATAA 872 CCGGGAAG CUGAUGAG X CGAA AGAAGCGC 2568 GCGCTTCT C CTTCCCGG 569 HUMGATAA 873 UCCCCGGG CUGAUGAG X CGAA AGGAGAAG 2569 CTTCTCCT T CCCGGGGA 570 HUMGATAA 874 GUCCCCGG CUGAUGAG X CGAA AAGGAGAA 2570 TTCTCCTT C CCGGGGAC 587 HUMGATAA 875 CCGCCAGG CUGAUGAG X CGAA ACCCGGUG 2571 CACCGGGT C CCTGGCGG 635 HUMGATAA 876 CACUGCUG CUGAUGAG X CGAA AGGCCGCA 2572 TGCGGCCT A CAGCAGTG 686 HUMGATAA 877 CGCGCCCG CUGAUGAG X CGAA ACUGCUCG 2573 CGAGCAGT A CGGGCGCG 701 HUMGATAA 878 AGCCCGCG CUGAUGAG X CGAA AGCCGGCG 2574 CGCCGGCT T CGCGGGCT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 879GACCCCGCCUGAUGAGXCGAAAAGCCGGC2575GCCGGCTTCGCGGGCTC702HUMG ATAA 880UGGAGUAGCUGAUGAGXCGAAAGCCCGCG2576CGCGGGCTCCTACTCCA710HUMG ATAA 881GGCUGGAGCUGAUGAGXCGAAAGGAGCCC2577GGGCTCCTACTCCAGCC713HUMG ATAA 882AGGGGCUGCUGAUGAGXCGAAAGUAGGAG2578CTCCTACTCCAGCCCCT716HUMG ATAA 883AAGCCGGGCUGAUGAGXCGAAAGGGGCUG2579CAGCCCCTACCCGGCTT725HUMG ATAA 884GGCCAUGUCUGAUGAGXCGAAAGCCGGGU2580ACCCGGCTTACATGGCC733HUMG ATAA 885CGGCCAUGCUGAUGAGXCGAAAAGCCGGG2581CCCGGCTTACATGGCCG734HUMG ATAA 755 HUMGATAA 886 CGGCCCAG CUGAUGAG X CGAA ACGCGCCC 2582 GGGCGCGT C CTGGGCCG 887GGCCGGCGCUGAUGAGXCGAAAGGCGGCG2583CGCCGCCTCCGCCGGCC779HUMG ATAA 791 HUMGATAA 888 XCGAAAGGGGCCG2584CGGCCCCTTCGACAGCCCUGAUGAG 792 HUMGATAA 889 GGGCUGUC CUGAUGAG X CGAA AAGGGGCC 2585 GGCCCCTT C GACAGCCC 890CUGUGCAGCUGAUGAGXCGAAACCGGGCU2586AGCCCGGTCCTGCACAG804HUMG ATAA 891CAUAUCGACUGAUGAGXCGAAAUUGGGGU2587ACCCCAATCTCGATATG853HUMG ATAA 892AACAUAUCCUGAUGAGXCGAAAGAUUGGG2588CCCAATCTCGATATGTT855HUMG ATAA 859 HUMGATAA CUGAUGAGGUCAAACA X 2589ATCTCGATATGTTTGACAUCGAGAU 863 HUMGATAA 894 AGUCGUCA CUGAUGAG X CGAA ACAUAUCG 2590 CGATATGT T TGACGACT 864 HUMGATAA 895 AAGUCGUC CUGAUGAG X CGAA AACAUAUC 2591 GATATGTT T GACGACTT 872 HUMGATAA 896 CUUCUGAG CUGAUGAG X CGAA AGUCGUCA 2592 TGACGACT T CTCAGAAG 873 HUMGATAA 897 CCUUCUGA CUGAUGAG X CGAA AAGUCGUC 2593 GACGACTT C TCAGAAGG 875 HUMGATAA 898 UGCCUUCU CUGAUGAG X CGAA AGAAGUCG 2594 CGACTTCT C AGAAGGCA 894 HUMGATAA 899 CCACAGUU CUGAUGAG X CGAA ACACACUC 2595 GAGTGTGT C AACTGTGG 907 HUMGATAA 900 GGUGGACA CUGAUGAG X CGAA AGCCCCAC 2596 GTGGGGCT A TGTCCACC 911 HUMGATAA 901 GCGGGGUG CUGAUGAG X CGAA ACAUAGCC 2597 GGCTATGT C CACCCCGT 921 HUMGATAA 902 CGCCUCCA CUGAUGAG X CGAA AGCGGGGU 2598 ACCCCGCT C TGGAGGCG 943 HUMGATAA 903 CAGAUAGU CUGAUGAG X CGAA ACCCGUCC 2599 GGACGGGT C ACTATCTG 947 HUMGATAA 904 UGCACAGA CUGAUGAG X CGAA AGUGACCC 2600 GGGTCACT A TCTGTGCA 949 HUMGATAA 905 GUUGCACA CUGAUGAG X CGAA AUAGUGAC 2601 GTCACTAT C TGTGCAAC 969 HUMGATAA 906 UUGUGGUA CUGAUGAG X CGAA AGGCCACA 2602 TGTGGCCT C TACCACAA 971 HUMGATAA 907 UCUUGUGG CUGAUGAG X CGAA AGAGGCCA 2603 TGGCCTCT A CCACAAGA 990 HUMGATAA 908 GGCCGGUU CUGAUGAG X CGAA AUGCCGUU 2604 AACGGCAT C AACCGGCC 1002 HUMGATAA 909 GGCUUGAU CUGAUGAG X CGAA AGCGGCCG 2605 CGGCCGCT C ATCAAGCC 1005 UGAGGCUUCUGAUGAGXCGAAAUGAGAGG2606CCGCTCATCAAGCCTCA910 911CCGGCGCUCUGAUGAGXCGAAAGGCUUGA2607TCAAGCCTCAGCGCCGG1012HUM GATAA 912GGGAGGCGCUGAUGAGXCGAAACAGCCGG2608CCGGCTGTCCGCCTCCC1025HUM GATAA 913CUCGGCGGCUGAUGAGXCGAAAGGCGGAC2609GTCCGCCTCCCGCCGAG1031HUM GATAA 1047 HUMGATAA 914 GCACAGGA CUGAUGAG X CGAA AGGCCCAC 2610 GTGGGCCT C TCCTGTGC 1049 HUMGATAA 915 UGGCACAG CUGAUGAG X CGAA AGAGGCCC 2611 GGGCCTCT C CTGTGCCA 1131 HUMGATAA 916 UUCAUGUA CUGAUGAG X CGAA AGGCCGCA 2612 TGCGGCCT C TACATGAA 1133 HUMGATAA 917 GCUUCAUG CUGAUGAG X CGAA AGAGGCCG 2613 CGGCCTCT A CATGAAGC 1143 HUMGATAA 918 ACCCCGUG CUGAUGAG X CGAA AGCUUCAU 2614 ATGAAGCT C CACGGGGT 1162 HUMGATAA 919 CAUUGCAA CUGAUGAG X CGAA AGGCCUGG 2615 CCAGGCCT C TTGCAATG 1164 HUMGATAA 920 CGCAUUGC CUGAUGAG X CGAA AGAGGCCU 2616 AGGCCTCT T GCAATGCG 1185 HUMGATAA 921 CUGGUUUG CUGAUGAG X CGAA AUCCCCUC 2617 GAGGGGAT C CAAACCAG 1219 HUMGATAA 922 CUUAGAUU CUGAUGAG X CGAA AUUCAGGU 2618 ACCTGAAT A AATCTAAG Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2,3,4, and 6) and the complementary sequences 923GUGUCUUACUGAUGAGXCGAAAUUUAUUC2619GAATAAATCTAAGACAC1223HUM GATAA 924UGGUGUCUCUGAUGAGXCGAAAGAUUUAU2620ATAAATCTAAGACACCA1225HUM GATAA 925GCCUGAAGCUGAUGAGXCGAAAGCUGCUG2621CAGCAGCTCCTTCAGGC1240HUM GATAA 926ACUGCCUGCUGAUGAGXCGAAAGGAGCUG2622CAGCTCCTTCAGGCAGT1243HUM GATAA 927CACUGCCUCUGAUGAGXCGAAAAGGAGCU2623AGCTCCTTCAGGCAGTG1244HUM GATAA 928GCGGGAGGCUGAUGAGXCGAAAGGCUCUC2624GAGAGCCTTCCTCCCGC1260HUM GATAA 929GGCGGGAGCUGAUGAGXCGAAAAGGCUCU2625AGAGCCTTCCTCCCGCC1261HUM GATAA 930GCUGGCGGCUGAUGAGXCGAAAGGAAGGC2626GCCTTCCTCCCGCCAGC1264HUM GATAA 1279 GUUGCUGGCUGAUGAGXCGAAAGCACCGC2627GCGGTGCTTCCAGCAAC931 932AGUUGCUGCUGAUGAGXCGAAAAGCACCG2628CGGTGCTTCCAGCAACT1280HUM GATAA 1289 HUMGATAA 933 CGUUGCUG CUGAUGAG X CGAA AGUUGCUG 2629 CAGCAACT C CAGCAACG 934CUUGAUGGCUGAUGAGXCGAAACGCAUCU2630AGATGCGTCCCATCAAG1327HUM GATAA 935UCCGUCUUCUGAUGAGXCGAAAUGGGACG2631CGTCCCATCAAGACGGA1332HUM GATAA 13521352HUMGATAA CUGAUGAGXCGAAACAGGCCA2632TGGCCTGTCATCTCACTAGUGAGAU 937CGUAGUGACUGAUGAGXCGAAAUGACAGG2633CCTGTCATCTCACTACG1355HUM GATAA 938CCCGUAGUCUGAUGAGXCGAAAGAUGACA2634TGTCATCTCACTACGGG1357HUM GATAA 939UGUGCCCGCUGAUGAGXCGAAAGUGAGAU2635ATCTCACTACGGGCACA1361HUM GATAA 1376 HUMGATAA 940 GGGACACG CUGAUGAG X CGAA AGCUGCUG 2636 CAGCAGCT C CGTGTCCC 1382 HUMGATAA 941 ACGUCUGG CUGAUGAG X CGAA ACACGGAG 2637 CTCCGTGT C CCAGACGT 1391 HUMGATAA 942 UGACUGAG CUGAUGAG X CGAA ACGUCUGG 2638 CCAGACGT T CTCAGTCA 1392 HUMGATAA 943 CUGACUGA CUGAUGAG X CGAA AACGUCUG 2639 CAGACGTT C TCAGTCAG 1394 HUMGATAA 944 CACUGACU CUGAUGAG X CGAA AGAACGUC 2640 GACGTTCT C AGTCAGTG 1398 HUMGATAA 945 AUCGCACU CUGAUGAG X CGAA ACUGAGAA 2641 TTCTCAGT C AGTGCGAT 1409 HUMGATAA 946 CAUGGCCA CUGAUGAG X CGAA ACAUCGCA 2642 TGCGATGT C TGGCCATG 1424 HUMGATAA 947 GGUGGAUG CUGAUGAG X CGAA AGGGCCCA 2643 TGGGCCCT C CATCCACC 1428 HUMGATAA 948 ACAGGGUG CUGAUGAG X CGAA AUGGAGGG 2644 CCCTCCAT C CACCCTGT 1437 HUMGATAA 949 GCCGCGAG CUGAUGAG X CGAA ACAGGGUG 2645 CACCCTGT C CTCTCGGC 1440 HUMGATAA 950 AGGGCCGA CUGAUGAG X CGAA AGGACAGG 2646 CCTGTCCT C TCGGCCCT 1442 HUMGATAA 951 UCAGGGCC CUGAUGAG X CGAA AGAGGACA 2647 TGTCCTCT C GGCCCTGA 1455 HUMGATAA 952 UGUGGGGA CUGAUGAG X CGAA AGCUUCAG 2648 CTGAAGCT C TCCCCACA 1457 HUMGATAA 953 CUUGUGGG CUGAUGAG X CGAA AGAGCUUC 2649 GAAGCTCT C CCCACAAG 1469 HUMGATAA 954 GAGACGCA CUGAUGAG X CGAA AGCCUUGU 2650 ACAAGGCT A TGCGTCTC 1475 HUMGATAA 955 UGACGGGA CUGAUGAG X CGAA ACGCAUAG 2651 CTATGCGT C TCCCGTCA 1477 HUMGATAA 956 GCUGACGG CUGAUGAG X CGAA AGACGCAU 2652 ATGCGTCT C CCGTCAGC 1482 HUMGATAA 957 GACUGGCU CUGAUGAG X CGAA ACGGGAGA 2653 TCTCCCGT C AGCCAGTC 1490 HUMGATAA 958 UCUGUGGA CUGAUGAG X CGAA ACUGGCUG 2654 CAGCCAGT C TCCACAGA 1492 HUMGATAA 959 GGUCUGUG CUGAUGAG X CGAA AGACUGGC 2655 GCCAGTCT C CACAGACC 1505 HUMGATAA 960 CCUGCUUG CUGAUGAG X CGAA AGCUGGUC 2656 GACCAGCT C CAAGCAGG 1517 HUMGATAA 961 UGUUCCAA CUGAUGAG X CGAA AGUCCUGC 2657 GCAGGACT C TTGGAACA 1519 HUMGATAA 962 ACUGUUCC CUGAUGAG X CGAA AGAGUCCU 2658 AGGACTCT T GGAACAGT 1528 HUMGATAA 963 CAAGACCA CUGAUGAG X CGAA ACUGUUCC 2659 GGAACAGT C TGGTCTTG 1533 HUMGATAA 964 UCGGCCAA CUGAUGAG X CGAA ACCAGACU 2660 AGTCTGGT C TTGGCCGA 1535 HUMGATAA 965 UGUCGGCC CUGAUGAG X CGAA AGACCAGA 2661 TCTGGTCT T GGCCGACA 1546 HUMGATAA 966 GUCCCCGU CUGAUGAG X CGAA ACUGUCGG 2662 CCGACAGT C ACGGGGAC Table III. Hammerhead ribozymes targeting GATA transcription factors (1, 2, 3, 4, and 6) and the complementary sequences 1557 GCAGUGAUCUGAUGAGXCGAAAUGUCCCC2663GGGGACATAATCACTGC967 968UACGCAGUCUGAUGAGXCGAAAUUAUGUC2664GACATAATCACTGCGTA1560HUM GATAA 969GGGAAGAUCUGAUGAGXCGAAACGCAGUG2665CACTGCGTAATCTTCCC1568HUM GATAA 970AGAGGGAACUGAUGAGXCGAAAUUACGCA2666TGCGTAATCTTCCCTCT1571HUM GATAA 971GAAGAGGGCUGAUGAGXCGAAAGAUUACG2667CGTAATCTTCCCTCTTC1573HUM GATAA 972GGAAGAGGCUGAUGAGXCGAAAAGAUUAC2668GTAATCTTCCCTCTTCC1574HUM GATAA 973GGAGGGAACUGAUGAGXCGAAAGGGAAGA2669TCTTCCCTCTTCCCTCC1578HUM GATAA 974GAGGAGGGCUGAUGAGXCGAAAGAGGGAA2670TTCCCTCTTCCCTCCTC1580HUM GATAA 975UGAGGAGGCUGAUGAGXCGAAAAGAGGGA2671TCCCTCTTCCCTCCTCA1581HUM GATAA 976AAUUUGAGCUGAUGAGXCGAAAGGGAAGA2672TCTTCCCTCCTCAAATT1585HUM GATAA 977AGGAAUUUCUGAUGAGXCGAAAGGAGGGA2673TCCCTCCTCAAATTCCT1588HUM GATAA 978CGUGCAGGCUGAUGAGXCGAAAUUUGAGG2674CCTCAAATTCCTGCACG1593HUM GATAA 979CCGUGCAGCUGAUGAGXCGAAAAUUUGAG2675CTCAAATTCCTGCACGG1594HUM GATAA 980UAUCCUCCCUGAUGAGXCGAAAGUCCCAG2676CTGGGAVTTGGAGGATA1613HUM GATAA 981UUCUUUGCCUGAUGAGXCGAAAUCCUCCA2677TGGAGGATAGCAAAGAA1621HUM GATAA 982GCCCCUGGCUGAUGAGXCGAAAGCCCAGG2678CCTGGGCTCCCAGGGGC1644HUM GATAA 983AGGCAGAGCUGAUGAGXCGAAAGGCCGGC2679GCCGGCCTCCTCTGCCT1659HUM GATAA 984ACCAGGCACUGAUGAGXCGAAAGGAGGCC2680GGCCTCCTCTGCCTGGT1662HUM GATAA 1671 HUMGATAA 985 GGAGUCAU CUGAUGAG X CGAA ACCAGGCA 2681 TGCCTGGT A ATGACTCC 1678 HUMGATAA 986 UUGUUCUG CUGAUGAG X CGAA AGUCAUUA 2682 TAATGACT C CAGAACAA 1703 HUMGATAA 987 UCGACUUC CUGAUGAG X CGAA AGUUUCUU 2683 AAGAAACT T GAAGTCGA 1709 HUMGATAA 988 AGAUUGUC CUGAUGAG X CGAA ACUUCAAG 2684 CTTGAAGT C GACAATCT 1716 HUMGATAA 989 CCUAACCA CUGAUGAG X CGAA AUUGUCGA 2685 TCGACAAT C TGGTTAGG 1721 HUMGATAA 990 CUUCCCCU CUGAUGAG X CGAA ACCAGAUU 2686 AATCTGGT T AGGGGAAG 1722 HUMGATAA 991 GCUUCCCC CUGAUGAG X CGAA AACCAGAU 2687 ATCTGGTT A GGGGAAGC 1737 HUMGATAA 992 GAAAAUCC CUGAUGAG X CGAA ACACCCGC 2688 GCGGGTGT T GGATTTTC 1742 HUMGATAA 993 UCUGAGAA CUGAUGAG X CGAA AUCCAACA 2689 TGTTGGAT T TTCTCAGA 1743 HUMGATAA 994 AUCUGAGA CUGAUGAG X CGAA AAUCCAAC 2690 GTTGGATT T TCTCAGAT 1744 HUMGATAA 995 CAUCUGAG CUGAUGAG X CGAA AAAUCCAA 2691 TTGGATTT T CTCAGATG 1745 HUMGATAA 996 GCAUCUGA CUGAUGAG X CGAA AAAAUCCA 2692 TGGATTTT C TCAGATGC 1747 HUMGATAA 997 AGGCAUCU CUGAUGAG X CGAA AGAAAAUC 2693 GATTTTCT C AGATGCCT 1756 HUMGATAA 998 AGCGUGUA CUGAUGAG X CGAA AGGCAUCU 2694 AGATGCCT T TACACGCT 1757 HUMGATAA 999 CAGCGUGU CUGAUGAG X CGAA AAGGCAUC 2695 GATGCCTT T ACACGCTG 1758 HUMGATAA 1000 UCAGCGUG CUGAUGAG X CGAA AAAGGCAU 2696 ATGCCTTT A CACGCTGA 1790 HUMGATAA 1001 UCGUGCUG CUGAUGAG X CGAA AGGGUGGG 2697 CCCACCCT T CAGCACGA 1971 HUMGATAA 1002 CUCGUGCU CUGAUGAG X CGAA AAGGGUGG 2698 CCACCCTT C AGCACGAG 1810 HUMGATAA 1003 ACAGGAGA CUGAUGAG X CGAA AUGCAGUG 2699 CACTGCAT C TCTCCTGT 1812 HUMGATAA 1004 UCACAGGA CUGAUGAG X CGAA AGAUGCAG 2700 CTGCATCT C TCCTGTGA 1814 HUMGATAA 1005 ACUCACAG CUGAUGAG X CGAA AGAGAUGC 2701 GCATCTCT C CTGTGAGT 1823 HUMGATAA 1006 AAGUCUCC CUGAUGAG X CGAA ACUCACAG 2702 CTGTGAGT T GGAGACTT 1831 HUMGATAA 1007 UGGGAAAG CUGAUGAG X CGAA AGUCUCCA 2703 TGGAGACT T CTTTCCCA 1832 HUMGATAA 1008 UUGGGAAA CUGAUGAG X CGAA AAGUCUCC 2704 GGAGACTT C TTTCCCAA 1834 HUMGATAA 1009 UCUUGGGA CUGAUGAG X CGAA AGAAGUCU 2705 AGACTTCT T TCCCAAGA 1835 HUMGATAA 1010 AUCUUGGG CUGAUGAG X CGAA AAGAAGUC 2706 GACTTCTT T CCCAAGAT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2.3,4, and 6) and the complementary sequences 1836 HUMGATAA CUGAUGAGXCGAAAAAGAAGU2707ACTTCTTTCCCAAGATGCAUCUUGG 1846 HUMGATAA 1012 GGGACAAG CUGAUGAG X CGAA ACAUCUUG 2708 CAAGATGT C CTTGTCCC 1013CAGGGGACCUGAUGAGXCGAAAGGACAUC2709GATGTCCTTGTCCCCTG1849HU MGATAA 1014ACGCAGGGCUGAUGAGXCGAAACAAGGAC2710GTCCTTGTCCCCTGCGT1852HU MGATAA 1015CAGUGGGGCUGAUGAGXCGAAACGCAGGG2711CCCTGCGTTCCCCACTG1861HU MGATAA 1016ACAGUGGGCUGAUGAGXCGAAAACGCAGG2712CCTGCGTTCCCCACTGT1862HU MGATAA 1017CCACGGUCCUGAUGAGXCGAAAGGCCACA2713TGTGGCCTAGACCGTGG1876HU MGATAA 1018CAAUGCAACUGAUGAGXCGAAACCCACGG2714CCGTGGGTTTTGCATTG1887HU MGATAA 1019ACAAUGCACUGAUGAGXCGAAAACCCACG2715CGTGGGTTTTGCATTGT1888HU MGATAA 1020CACAAUGCCUGAUGAGXCGAAAAACCCAC2716GTGGGTTTTGCATTGTG1889HU MGATAA 1021AGAAACACCUGAUGAGXCGAAAUGCAAAA2717TTTTGCATTGTGTTTCT1894HU MGATAA 1022GUGCUAGACUGAUGAGXCGAAACACAAUG2718CATTGTGTTTCTAGCAC1899HU MGATAA 1023GGUGCUAGCUGAUGAGXCGAAAACACAAU2719ATTGTGTTTCTAGCACC1900HU MGATAA 1024CGGUGCUACUGAUGAGXCGAAAAACACAA2720TTGTGTTTCTAGCACCG1901HU MGATAA 1025UUCGGUGCCUGAUGAGXCGAAAGAAACAC2721GTGTTTCTAGCACCGAA1903HU MGATAA 1026UGUUCUCACUGAUGAGXCGAAAUCCUUCG2722CGAAGGATCTGAGAACA1916HU MGATAA 1955 HUMGATAA 1027 UCGGGCUG CUGAUGAG X CGAA AGCAGGGG 2723 CCCCTGCT C CAGCCCGA 1974 HUMGATAA 1028 GGCAAACA CUGAUGAG X CGAA AUGCCGUC 2724 GACGGCAT C TGTTTGCC 1978 HUMGATAA 1029 ACAUGGCA CUGAUGAG X CGAA ACAGAUGC 2725 GCATCTGT T TGCCATGT 1979 HUMGATAA 1030 UACAUGGC CUGAUGAG X CGAA AACAGAUG 2726 CATCTGTT T GCCATGTA 1987 HUMGATAA 1031 CAUCCAGG CUGAUGAG X CGAA ACAUGGCA 2727 TGCCATGT A CCTGGATG 2021 HUMGATAA 1032 GAUGGGGC CUGAUGAG X CGAA AGGGCCUG 2728 CAGGCCCT T GCCCCATC 2029 HUMGATAA 1033 AGCGGAUG CUGAUGAG X CGAA AUGGGGCA 2729 TGCCCCAT C CATCCGCT 1034CUCAAGCGCUGAUGAGXCGAAAUGGAUGG2730CCATCCATCCGCTTGAG2033HU MGATAA 1035CAUGCCUCCUGAUGAGXCGAAAGCGGAUG2731CATCCGCTTGAGGCATG2038HU MGATAA 1036GUAUUAGGCUGAUGAGXCGAAAUGCAGGG2732CCCTGCATCCCTAATAC2061HU MGATAA 2065 HUMGATAA 1037 UUUGGUAU CUGAUGAG X CGAA AGGGAUGC 2733 GCATCCCT A ATACCAAA 2068 HUMGATAA 1038 AGAUUUGG CUGAUGAG X CGAA AUUAGGGA 2734 TCCCTAAT A CCAAATCT 2075 HUMGATAA 1039 UGGAGUCA CUGAUGAG X CGAA AUUUGGUA 2735 TACCAAAT C TGACTCCA 2081 HUMGATAA 1040 CAGUUUUG CUGAUGAG X CGAA AGUCAGAU 2736 ATCTGACT C CAAAACTG 2120 HUMGATAA 1041 UCCCCAGG CUGAUGAG X CGAA AGUGCUCA 2737 TGAGCACT T CCTGGGGA 2121 HUMGATAA 1042 CUCCCCAG CUGAUGAG X CGAA AAGUGCUC 2738 GAGCACTT C CTGGGGAG 2132 HUMGATAA 1043 UGCCCCUG CUGAUGAG X CGAA AGCUCCCC 2739 GGGGAGCT A CAGGGGCA 2143 HUMGATAA 1044 GGUGGGUU CUGAUGAG X CGAA AGUGCCCC 2740 GGGGCACT T AACCCACC 2144 HUMGATAA 1045 UGGUGGGU CUGAUGAG X CGAA AAGUGCCC 2741 GGGCACTT A ACCCACCA 2164 HUMGATAA 1046 AUUUUGAU CUGAUGAG X CGAA AGGCUGCG 2742 CGCAGCCT C ATCAAAAT 2167 HUMGATAA 1047 UGCAUUUU CUGAUGAG X CGAA AUGAGGCU 2743 AGCCTCAT C AAAATGCA 2186 HUMGATAA 1048 UGGGGGAG CUGAUGAG X CGAA AGUUGCCA 2744 TGGCAACT T CTCCCCCA 2187 HUMGATAA 1049 CUGGGGGA CUGAUGAG X CGAA AAGUUGCC 2745 GGCAACTT C TCCCCCAG 2189 HUMGATAA 1050 ACCUGGGG CUGAUGAG X CGAA AGAAGUUG 2746 CAACTTCT C CCCCAGGT 2202 HUMGATAA 1051 GCAGGGGG CUGAUGAG X CGAA AGGCACCU 2747 AGGTGCCT T CCCCCTGC 2203 HUMGATAA 1052 AGCAGGGG CUGAUGAG X CGAA AAGGCACC 2748 GGTGCCTT C CCCCTGCT 21 HSGATA6PR 1053 GCUCGCCG CUGAUGAG X CGAA AGGGUGCC 2749 GGCACCCT T CGGCGAGC 22 HSGATA6PR 1054 CGCUCGCC CUGAUGAG X CGAA AAGGGUGC 2750 GCACCCTT C GGCGAGCG Table III. Hammerhead ribozymes targeting GATA transcription factors (L, 2,3,4, and 6) and the complementary sequences 1055CCUAAACACUGAUGAGXCGAAACAGCGCU2751AGCGCTGTTTGTTTAGG35HSGA TA6PR 36 HSGATA6PR 1056 XCGAAAACAGCGC2752GCGCTGTTTGTTTAGGGCUGAUGAG 1057GAGCCCUACUGAUGAGXCGAAACAAACAG2753CTGTTTGTTTAGGGCTC39HSGA TA6PR 1058CGAGCCCUCUGAUGAGXCGAAAACAAACA2754TGTTTGTTTAGGGCTCG40HSGA TA6PR 1059CCGAGCCCCUGAUGAGXCGAAAAACAAAC2755GTTTGTTTAGGGCTCGG41HSGA TA6PR 1060GACUCACCCUGAUGAGXCGAAAGCCCUAA2756TTAGGGCTCGGTGAGTC47HSGA TA6PR 1061CCUGAUUGCUGAUGAGXCGAAACUCACCG2757CGGTGAGTCCAATCAGG55HSGA TA6PR 1062GGGCUCCUCUGAUGAGXCGAAAUUGGACU2758AGTCCAATCAGGAGCCC60HSGA TA6PR 1063UGCCGGAACUGAUGAGXCGAAACUGCAGC2759GCTGCAGTTTTCCGGCA79HSGA TG6PR 1064CUGCCGGACUGAUGAGXCGAAAACUGCAG2760CTGCAGTTTTCCGGCAG80HSGA TA6PR 1065UCUGCCGGCUGAUGAGXCGAAAAACUGCA2761TGCAGTTTTCCGGCAGA81HSGA TA6PR 1066CUCUGCCGCUGAUGAGXCGAAAAAACUGC2762GCAGTTTTTCGGCAGAG82HSGA TA6PR 95 GCGCCUCUCUGAUGAGXCGAAACUGCUCU2763AGAGCAGTAAGAGGCGC1067 106 GGAGAGAGCUGAUGAGXCGAAAGGCGCCU2764AGGCGCCTCCTCTCTCC1068 109 HSGATA6PR 1069 AAAGGAGA CUGAUGAG X CGAA AGGAGGCG 2765 CGCCTCCT C TCTCCTTT 111 HSGATA6PR 1070 AAAAAGGA CUGAUGAG X CGAA AGAGGAGG 2766 CCTCCTCT C TCCCTTTT 1071AUAAAAAGCUGAUGAGXCGAAAGAGAGGA2767TCCTCTCTCCTTTTTAT113HSG ATA6PR 1072UGAAUAAACUGAUGAGXCGAAAGGAGAGA2768TCTCTCCTTTTTATTCA116HSG ATA6PR 1073GUGAAUAACUGAUGAGXCGAAAAGGAGAG2769CTCTCCTTTTTATTCAC117HSG ATA6PR 1074GGUGAAUACUGAUGAGXCGAAAAAGGAGA2770TCTCCTTTTTATTCACC118HSG ATA6PR 1075UGGUGAAUCUGAUGAGXCGAAAAAAGGAG2771CTCCTTTTTATTCACCA119HSG ATA6PR 1076CUGGUGAACUGAUGAGXCGAAAAAAAGGA2772TCCTTTTTATTCACCAG120HSG ATA6PR 1077UGCUGGUGCUGAUGAGXCGAAAUAAAAAG2773CTTTTTATTCACCAGCA122HSG ATA6PR 1078CUGCUGGUCUGAUGAGXCGAAAAUAAAAA2774TTTTTATTCACCAGCAG123HSG ATA6PR 1079GCGAGCGCUUGAUGAGXCGAAAGUCCGGG2775CCCGGACTCGCGCTCGC152HSG ATA6PR 158158HSGATA6PR 1080 CAGCGGGC CUGAUGAG X CGAA AGCGCGAG 2776 CTCGCGCT C GCCCGCTG 174 HSGATA6PR 1081 GAGAAGCC CUGAUGAG X CGAA AGGGCGCC 2777 GGCGCCCT C GGCTTCTC 179 HSGATA6PR 1082 GCGGAGAG CUGAUGAG X CGAA AGCCGAGG 2778 CCTCGGCT T CTCTCCGC 180 HSGATA6PR 1083 CGCGGAGA CUGAUGAG X CGAA AAGCCGAG 2880 CTCGGCTT C TCTCCGCG 182 HSGATA6PR 1084 GGCGCGGA CUGAUGAG X CGAA AGAAGCCG 2780 CGGCTTCT C TCCGCGCC 184 HSGATA6PR 1085 CAGGCGCG CUGAUGAG X CGAA AGAGAAGC 2781 GCTTCTCT C CGCGCCTG 203 HSGATA6PR 1086 CCGCGGCG CUGAUGAG X CGAA AGGGUGCU 2782 AGCACCCT C CGCCGCGG 216 HSGATA6PR 1087 GCAUGGAG CUGAUGAG X CGAA ACGGCCGC 2783 GCGGCCGT T CTCCATGC 217 HSGATA6PR 1088 CGCAUGGA CUGAUGAG X CGAA AACGGCCG 2784 CGGCCGTT C TCCATGCG 219 HSGATA6PR 1089 UGCGCAUG CUGAUGAG X CGAA AGAACGGC 2785 GCCGTTCT C CATGCGCA 246 HSGATA6PR 1090 CUGACGUC CUGAUGAG X CGAA AGCUCCUC 2786 GAGGAGCT A GACGTCAG 252 HSGATA6PR 1091 UCCAAGCU CUGAUGAG X CGAA ACGUCUAG 2787 CTAGACGT C AGCTIGGA 257 HSGATA6PR 1092 GCCGCUCC CUGAUGAG X CGAA AGCUGACG 2788 CGTCAGCT T GGAGCGGC 285 HSGATA6PR 1093 CGUCAGUC CUGAUGAG X CGAA AGGCCAUC 2789 GATGGCCT T GACTGACG 306 HSGATA6PR 1094 GCUUCGGC CUGAUGAG X CGAA AGCACCAG 2790 CTGGTGCT T GCCGAAGC 318 HSGATA6PR 1095 CGGCCCCG CUGAUGAG X CGAA AGCGCUUC 2791 GAAGCGCT T CGGGGCOG 319 HSGATA6PR 1096 GCGGCCCC CUGAUGAG X OGAA AAGCGCUU 2792 AAGCGCTT C GGGGCOGC 248 HSGATA6PR 1097 AGGCUCUG CUGAUGAG X OGAA AGUCGCUG 2793 CAGCGACT C CAGAGCCT 357 HSGATA6PR 1098 GCGCUGGA CUGAUGAG X CGAA AGGCUCUG 2794 CAGAGCCT T TCCAGCGC Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1099CGCGCUGGCUGAUGAGXCGAAAAGGCUCU2795AGAGCCTTTCCAGCGCG358HSG ATA6PR 1100CCGCGCUGCUGAUGAGXCGAAAAAGGCUC2796GAGCCTTTCCAGCGCGG359HSG ATA6PR 1101GCGGCGUGCUGAUGAGXCGAAAGGGCUCC2797GGAGCCCTCCGCGCCGC375HSG ATA6PR 1102GAGGGGGGCUGAUGAGXCGAAAGGCGGCG2798CGCCGCCTTCCCCCATC386HSG ATA6PR 1103AGAUGGGGCUGAUGAGXCGAAAAGGCGGC2799GCCGCCTTCCCCCATCT387HSG ATA6PR 1104GAGGAAGACUGAUGAGXCGAAAUGGGGGA2800TCCCCCATCTCTTCCTC394HSG ATA6PR 1105ACGAGGAACUGAUGAGXCGAAAGAUGGGG2801CCCCATCTCTTCCTCGT396HSG ATA6PR 1106GGACGAGGCUGAUGAGXCGAAAGAGAUGG2802CCATCTCTTCCTOGTOC398HSG ATA6PR 1107AGGACGAGCUGAUGAGXCGAAAAGAGAUG2803CATCTCTTCCTCGTCCT399HSG ATA6PR 1108AGGAGGACCUGAUGAGXCGAAAGGAAGAG2804CTCTTCCTCGTCCTCCT402HSG ATA6PR 1109AGGAGGAGCUGAUGAGXCGAAACGAGGAA2805TTCCTCGTCCTCCTCCT405HSG ATA6PR 1110AGCAGGAGCUGAUGAGXCGAAAGGACGAG2806CTCGTCCTCCTCCTGCT408HSG ATA6PR 411 GGGAGCAGCUGAUGAGXCGAAAGGAGGAC2807GTCCTCCTCCTGCTCCC1111 1112CGCCCCGGCUGAUGAGXCGAAAGCAGGAG2808CTCCTGCTCCCGGGGCG417HSG ATA6PR 1113GUCCAGCUCUGAUGAGXCGAAAGGCGUCC2809GGACGCCTCAGCTCGAC467HSG ATA6PR 1114UCCGUGUCCUGAUGAGXCGAAAGCUGAGG2810CCTCAGCTCGACACGGA472HSG ATA6PR 1115GCAGCAGCCUGAUGAGXCGAAAGCGGGOC2811GGCCCGCTCGCTGCTGC507HSG ATA6PR 1116UAGGAACUCUGAUGAGXCGAAAGCAGCAG2812CTGCTGCTCAGTTCCTA517HSG ATA6PR 1117AGCGUAGGCUGAUGAGXCGAAACUGAGCA2813TGCTCAGTTCCTACGCT521HSG ATA6PR 1118AAGCGUAGCUGAUGAGXCGAAAACUGAGC2814GCTCAGTTCCTACGCTT522HSG ATA6PR 1119GCGAAGCGCUGAUGAGXCGAAAGGAACUG2815CAGTTCCTACGCTTCGC525HSG ATA6PR 1120GGGAUGCGCUGAUGAGXCGAAAGCGUAGG2816CCTACGCTTCGCATCCC530HSG ATA6PR 1121AGGGAUGCCUGAUGAGXCGAAAAGCGUAG2817CTACGCTTCGCATCCCT531HSG ATA6PR 1122CCCGAAGGCUGAUGAGXCGAAAUGCGAAG2818CTTCGCATCCCTTCGGG536HSG ATA6PR 1123GAGCCCCGCUGAUGAGXCGAAAGGGAUGC2819GCATCCCTTCGGGGCTC540HSG ATA6PR 541 HSGATA6PR 1124 XCGAAAAGGGAUG2820CATCCCTTCGGGGCTCCCUGAUGAG 1125UCCGUGGGCUGAUGAGXCGAAAGCCCCGA2821TCGGGGCTCCCCACGGA548HSG ATA6PR 1126AGGCGCCGCUGAUGAGXCGAAAGGUCCGU2822ACGGACCTTCGGCGCCT560HSG ATA6PR 1127CAGGCGCCCUGAUGAGXCGAAAAGGUCCG2823CGGACCTTTGGCGCCTG561HSG ATA6PR 1128GGGCCCGCCUGAUGAGXCGAAACCCCAGG2824CCTGGGGTCGCGGGCCC574HSG ATA6PR 1129CCCAGCUCCUGAUGAGXCGAAACAGGUUG2825CAACCTGTCGAGCTGGG597HSG ATA6PR 1130ACAGCAGCCUGAUGAGXCGAAAGUCCUCC2826GGAGGACTTGCTGCTGT612HSG ATA6PR 1131GGUCAGUGCUGAUGAGXCGAAACAGCAGC2827GCTGCTGTTCACTGACC621HSG ATA6PR 1132AGGUCAGUCUGAUGAGXCGAAAACAGCAG2828CTGCTGTTCACTGACCT622HSG ATA6PR 1133GCUUGGUCCUGAUGAGXCGAAAGGUCAGU2829ACTGACCTCGACCAAGC631HSG ATA6PR 1134CGCGGCUGCUGAUGAGXCGAAACCACAGC2830GCTGTGGTCCAGCCGCG666HSG ATA6PR 1135CGGGUGCGCUGAUGAGXCGAAAGGGGCUC2831GAGCCCCTTCGCACCCG693HSG ATA6PR 1136UCGGGUGCCUGAUGAGXCGAAAAGGGGCU2832AGCCCCTTCGCACCCGA694HSG ATA6PR 1137GGGUCUGGCUGAUGAGXCGAAACAUCUCC2833GGAGATGTACCAGACCC720HSG ATA6PR 1138AGAGCGGCCUGAUGAGXCGAAAGGGUCUG2834CAGACCCTCGCCGCTCT730HSG ATA6PR 1139GCUGGAGACUGAUGAGXCGAAAGCGGCGA2835TCGCCGCTCTCTCCAGC737HSG ATA6PR 1140UGGCUGGACUGAUGAGXCGAAAGAGCGGC2836GCCGCTCTCTCCAGCCA739HSG ATA6PR 1141CCUGGCUGCUGAUGAGXCGAAAGAGAGCG2837CGCTCTCTCCAGCCAGG741HSG ATA6PR 1142GGCGGCCGCUGAUGAGXCGAAACCCUGGC2838GCCAGGGTCCGGCCGCC752HSG ATA6PR Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1143CGCCGUCGCUGAUGAGXCGAAAGGCGGCC2839GGCCGCCTACGACGGCG762HSG ATA6PR 1144AGUGCACGCUGAUGAGXCGAAAGCCGCCG2940CGGCGGCTTCGTGCACT783HSG ATA6PR 1145GAGUGCACCUGAUGAGXCGAAAAGCCGCC2841GGCGGCTTCGTGCACTC784HSG ATA6PR 1146CGGCCGCACUGAUGAGXCGAAAGUGCACG2842CGTGCACTTTGCGGCCG792HSG ATA6PR 1147AGACCGGGCUGAUGAGXCGAAAGCUGGCC2843GGCCAGCTCCCCGGTCT831HSG ATA6PR 1148GGCACGUACUGAUGAGXCGAAACCGGGGA2844TCCCCGGTCTACGTGCC838HSG ATA6PR 1149UGGGCACGCUGAUGAGXCGAAAGACCGGG2845CCCGGTCTACGTGCCCA840HSG ATA6PR 1150CAGCAUGGCUGAUGAGXCGAAACCCACGC2846GCGTGGGTTCCATGCTG863HSG ATA6PR 1151GCAGCAUGCUGAUGAGXCGAAAACCCAGC2847CGTGGGTTCCATGCTGC864HSG ATA6PR 1152UGGUACGGCUGAUGAGXCGAAAGGCCGGG2848CCCGGCCTACCGTACCA880HSG ATA6PR 1153GCAGGUGGCUGAUGAGXCGAAACGGUAGG2849CCTACCGTACCACCTGC885HSG ATA6PR 1154GACUGCCCCUGAUGAGXCGAAACCCCUGC2850GCAGGGGTCGGGCAGTG900HSG ATA6PR 1155CGAGGCCUCUGAUGAGXCGAAAGGCCAGC2851GCTGGCCTCAGGCCTCG956HSG ATA6PR 963 HSGATA6PR 1156 UGUCGGCC CUGAUGAG X CGAA AGGCCUGA 2852 TCAGGCCT C GGCCGACA 977 HSGATA6PR 1157 GCCGUAUG CUGAUGAG X CGAA AGGGCUGU 2853 ACAGCCCT C CATACGGC 981 HSGATA6PR 1158 CGCUGCCG CUGAUGAG X CGAA AUGGAGGG 2854 CCCTCCAT A CGGCAGCG 1038 HSGATA6PR 1159 CCGCGGCU CUGAUGAG X CGAA AGCCAGCG 2855 CGCTGGCT C AGCCGCGG 1054 HSGATA6PR 1160 CGCGCCGA CUGAUGAG X CGAA ACGUGCGC 2856 GCGCACGT C TCGGCGCG 1056 HSGATA6PR 1161 AGCGCGCC CUGAUGAG X CGAA AGACGUGC 2857 GCACGTCT C GGCGCGCT 1065 HSGATA6PR 1162 AGUAGGGG CUGAUGAG X CGAA AGCGCGCC 2858 GGCGCGCT T CCCCTACT 1066 HSGATA6PR 1163 GAGUAGGG CUGAUGAG X CGAA AAGCGCGC 2859 GCGCGCTT C CCCTACTC 1164UGGGAGAGCUGAUGAGXCGAAAGGGGAAG2860CTTCCCCTACTCTCCCA1071HS GATA6PR 1165GGCUGGGACUGAUGAGXCGAAAGUAGGGG2861CCCCTACTCTCCCAGCC1074HS GATA6PR 1166CGGGCUGGCUGAUGAGXCGAAAGAGUAGG2862CCTACTCTCCCAGCCCG1076HS GATA6PR 1120 HSGATA6PR 1167 GCCGCGUA CUGAUGAG X CGAA ACUCCCGG 2863 CCGGGAGT T TACGCGGC 1121 HSGATA6PR 1168 CGCCGCGU CUGAUGAG X CGAA AACUCCCG 2864 CGGGAGTT T ACGCGGOG 1122 HSGATA6PR 1169 CCGCCGCG CUGAUGAG X CGAA AAACUCCC 2865 GGGAGTTT A CGCGGCGG 1172 HSGATA6PR 1170 CGCCAGGC CUGAUGAG X CGAA ACUGCCGC 2866 GCGGCAGT A GCCTGGCG 1206 HSGATA6PR 1171 GCGAGCUG CUGAUGAG X CGAA ACUGGGGC 2867 GCCCCAGT A CAGCTOGC 1212 HSGATA6PR 1172 CCGACAGC CUGAUGAG X CGAA AGCUGUAC 2868 GTACAGCT C GCTGTCGG 1218 HSGATA6PR 1173 GCGCGGCC CUGAUGAG X CGAA ACAGCGAG 2869 CTCGCTGT C GGCCGCGC 1245 HSGATA6PR 1174 GGUGGUGG CUGAUGAG X CGAA ACGUCCCG 2870 CGGGACGT A CCACCACC 1277 HSGATA6PR 1175 GGGGCUCG CUGAUGAG X CGAA AUGGUGGU 2871 ACCACCAT C GGAGCCCC 1287 HSGATA6PR 1176 AGGGCGAG CUGAUGAG X CGAA AGGGGCUC 2872 GAGCCCCT A CTCGCCCT 1290 HSGATA6PR 1177 CGUAGGGC CUGAUGAG X CGAA AGUAGGGG 2873 CCCCTACT C GCCCTACG 1296 HSGATA6PR 1178 CCCCCACG CUGAUGAG X CGAA AGGGCGAG 2874 CTCGCCCT A CGTGGGGG 1338 HSGATA6PR 1179 GGGUCUCG CUGAUGAG X CGAA AGGGUCCG 2875 CGGACCCT A CGAGACCC 1339 HSGATA6PR 1180 GGGGUCUC CUGAUGAG X CGAA AAGGGUCC 2876 GGACCCTT C GAGACCCC 1387 HSGATA6PR 1181 GGCACCGG CUGAUGAG X CGAA AGCGGGGC 2877 GCCCCGCT C CCGGTGCC 1403 HSGATA6PR 1182 UGCACUGG CUGAUGAG X CGAA ACCCCGGG 2878 CCCGGGGT C CCAGTGCA 1431 HSGATA6PR 1183 GGCUCUCG CUGAUGAG X CGAA ACAGGUCC 2879 GGACCTGT C CGAGAGCC 1461 HSGATA6PR 1184 UCUGGAUG CUGAUGAG X CGAA AGCCGCAG 2880 CTGCGGCT C CATCCAGA 1465 HSGATA6PR 1185 GGCGUCUG CUGAUGAG X CGAA AUGGAGCC 2881 GGCTCCAT C CAGACGCC 1503 HSGATA6PR 1186 UGCACAGG CUGAUGAG X CGAA AGUGGCCG 2882 CGGCCACT A CCTGTGCA Table III. Hammerhead ribozymes targeting GATA transcription factors (1, X, 3,4, and 6) and the complementary sequences 1525 HSGATA6PR 1187 UUGCUGUA CUGAUGAG X CGAA AGCCCGCA 2883 TGCGGGCT C TACAGCAA 1188UCUUGCUGCUGAUGAGXCGAAAGAGCCCG2884CGGGCTCTACAGCAAGA1527HS GATA6PR 1189GGCCGGCUCUGAUGAGXCGAAAGGCCGUU2885AACGGCCGCAGCCGGCC1546HS GATA6PR 1190GGCUUGAUCUGAUGAGXCGAAAGGGGCCG2886CGGCCCCTCATCAAGCC1558HS GATA6PR 1191UGCGGCUUCUGAUGAGXCGAAAUGAGGGG2887CCCCTCATCAAGCCGCA1561HS GATA6PR 1192CCGUGAUGCUGAUGAGXCGAAAGGCACGC2888GCGTGCCTTCATCACGG1583HS GATA6PR 1193GCCGUGAUCUGAUGAGXCGAAAUGAAGGC2890GCCTTCATCACGGCGGC1584HS GATA6PR 1194GCCGCCGUCUGAUGAGXCGAAAUGAAGGC2890GCCTTCATCACGGCGGC1587HS GATA6PR 1195GACAAUCCCUGAUGAGXCGAAAGCCGCCG2891CGGCGGCTTGGATTGIC1597HS GATA6PR 1196CACAGGACCUGAUGAGXCGAAAUCCAAGC2892GCTTGGATTGTCCTGTG1602HS GATA6PR 1197UGGCACAGCUGAUGAGXCGAAACAAUCCA2893TGGATTGTCCTGTGCCA1605HS GATA6PR 1198UGUGGUGUCUGAUGAGXCGAAACAGUUGG2894CCAACTGTCACACCACA1619HS GATA6PR 1199UAAGGUGGCUGAUGAGXCGAAAGUUGUGG2895CCACAACTACCACCTTA1631HS GATA6PR 1200UGCGCCAUCUGAUGAGXCGAAAGGUGGUA2896TACCACCTTATGGCGCA1638HS GATA6PR 1201CUGCGCCACUGAUGAGXCGAAAAGGUGGU2897ACCACCTTATGGCGCAG1639HS GATA6PR 1202GAGUCCACCUGAUGAGXCGAAAGCAUUGC2898GCAATGCTTGTGGACTC1679HS GATA6PR 1203UUCAUGUACUGAUGAGXCGAAAGUCCACA2899TGTGGACTCTACATGAA1687HS GATA6PR 1204GUUUCAUGCUGAUGAGXCGAAAGAGUCCA2900TGGACTCTACATGAAAC1689HS GATA6PR 1205ACCCCAUGCUGAUGAGXCGAAAGUUUCAU2901ATGAAACTCCATGGGGT1699HS GATA6PR 1206UUCAUAGCCUGAUGAGXCGAAAGUGGUCU2902AGACCACTTGCTATGAA1720HS GATA6PR 1207UUUUUUCACUGAUGAGXCGAAAGCAAGUG2903CACTTGCTATGAAAAAA1724HS GATA6PR 1208CUGGUUUGCUGAUGAGXCGAAAUUCCCUC2904GAGGGAATACAAACCAG1741HS GATA6PR 17421742HSGATA6PR 1209 XCGAAAAUUCCCU2905AGGGAATTAAGAACATACUGAUGAG 17631763HSGATA6PR 1210 XCGAAAGGUUUUC2906GAAAACCTAAGAACATACUGAUGAG 1771 HSGATA6PR 1211 XCGAAAUGUUCUU2907AAGAACATAAATAAATCCUGAUGAG 1775 CUUUGAUUCUGAUGAGXCGAAAUUUAUGU2908ACATAAATAAATCAAAG1212 1213AAGUCUUUCUGAUGAGXCGAAAUUUAUUU2909AAATAAATCAAAGACTT1779HS GATA6PR 1214ACCAGAGCCUGAUGAGXCGAAAGUCUUUG2910CAAAGACTTGCTCTGGT1787HS GATA6PR 1215UAUUACCACUGAUGAGXCGAAAGCAAGUC2911GACTTGCTCTGGTAATA1791HS GATA6PR 1216AUUGCUAUCUGAUGAGXCGAAACCAGAGC2912GCTCTGGTAATAGCAAT1796HS GATA6PR 1217AUUAUUGCCUGAUGAGXCGAAAUUACCAG2913CTGGTAATAGCAATAAT1799HS GATA6PR 1218AAUGGAAUCUGAUGAGXCGAAAUUGCUAU2914ATAGCAATAATTCCATT1805HS GATA6PR 1808 GGGAAUGGCUGAUGAGXCGAAAUUAUUGC2915GCAATAATTCCATTCCC1219 1220UGGGAAUGCUGAUGAGXCGAAAAUUAUUG2916CAATAATTCCATTCCCA1809HS GATA6PR 1221GUCAUGGGCUGAUGAGXCGAAAUGGAAUU2917AATTCCATTCCCATGAC1813HS GATA6PR 1222AGUCAUGGCUGAUGAGXCGAAAAUGGAAU2918ATTCCATTCCCATGACT1814HS GATA6PR 1223GGAAGUUGCUGAUGAGXCGAAAGUCAUGG2919CCATGACTCCAACTTCC1823HS GATA6PR 1224AGAGGUGGCUGAUGAGXCGAAAGUUGGAG2920CTCCAACTTCCACCTCT1829HS GATA6PR 1225AAGAGGUGCUGAUGAGXCGAAAAGUUGGA2921TCCAACTTCCACCTCTT1830HS GATA6PR 1226AGUUAGAACUGAUGAGXCGAAAGGUGGAA2922TTCCACCTCTTCTAACT1836HS GATA6PR 1227UGAGUUAGCUGAUGAGXCGAAAGAGGUGG2923CCACCTCTTCTAACTCA1838HS GATA6PR 1228CUGAGUUACUGAUGAGXCGAAAAGAGGUG2924CACCTCTTCTAACTCAC1839HS GATA6PR 1841 AUCUGAGUCUGAUGAGXCGAAAGAAGAGG2925CCTCTTCCAACTCAGAT1229 1230AAUCAUCUCUGAUGAGXCGAAAGUUAGAA2926TTCTAACTCAGATGATT1845HS GATA6PR Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1231UUUGCUGCCUGAUGAGXCGAAAUCAUCUG2927CAGATGATTGCAGCAAA1853HS GATA6PR 1232GGGGGAAGCUGAUGAGXCGAAAUUUUUGC2928GCAAAAATACTTCCCCC1865HS GATA6PR 1233UGUGGGGGCUGAUGAGXCGAAAGUAUUUU2929AAAATACTTCCCCCACA1868HS GATA6PR 1234UUGUGGGGCUGAUGAGXCGAAAAGUAUUU2930AAATACTTCCCCCACAA1869HS GATA6PR 1235UGAGGCUGCUGAUGAGXCGAAAUUGGUGC2933GCACCAATCCCGAGAAC1886HS GATA6PR 1236CCGCCCCUCUGAUGAGXCGAAAGGCUGUA2932TACAGCCTCAGGGGCGG1893HS GATA6PR 1237GUUCUCGGCUGAUGAGXCGAAAUUGGUGC2933GCACCAATCCCGAGAAC1940HS GATA6PR 1238GAAUGCUUCUGAUGAGXCGAAAGCUCGCU2934AGCGAGCTCAAGTATTC1957HS GATA6PR 1239GACCCGAACUGAUGAGXCGAAACUUGAGC2935GCTCAAGTATTCGGGTC1962HS GATA6PR 1964 UUGACCCGCUGAUGAGXCGAAAUACUUGA2936TCAAGTATTCGGGTCAA1240 1241CUUGACCCCUGAUGAGXCGAAAAUACUUG2937CAAGTATTCGGGTCAAG1965HS GATA6PR 1242CCCAUCUUCUGAUGAGXCGAAACCCGAAU2938ATTCGGGTCAAGATGGG1970HS GATA6PR 1243CCUAUGUACUGAUGAGXCGAAAGCCCAUC2939GATGGGCTCTACATAGG1981HS GATA6PR 1244CGCCUAUGCUGAUGAGXCGAAAGAGCCCA2940TGGGGTCTACATAGGCG1983HS GATA6PR 1245CUGACGCCCUGAUGAGXCGAAAUGUAGAG2941CTCTACATAGGCGTCAG1987HS GATA6PR 1246GCCAGACUCUGAUGAGXCGAAACGCCUAU2942ATAGGCGTCAGTCTCGC1993HS GATA6PR 1247CGAGGCGACUGAUGAGXCGAAACUGACGC2943GCGTCAGTCTCGCCTCG1997HS GATA6PR 1248GGCGAGGCCUGAUGAGXCGAAAGACUGAC2944GTCAGTCTCGCCTCGOC1999HS GATA6PR 1249CGGCCGGCCUGAUGAGXCGAAAGGCGAGA2945TCTCGCCTCGCCGGCCG2004HS GATA6PR 1250GAGGACGUCUGAUGAGXCGAAACUUCGGC2946GCCGAAGTCACGTCCTC2017HS GATA6PR 1251GCACGGAGCUGAUGAGXCGAAACGUGACU2947AGTCACGTCCTCCGTGC2022HS GATA6PR 1252GUCGCACGCUGAUGAGXCGAAAGGACGUG2948CACGTCCTCCGTGCGAC2025HS GATA6PR 1253GCACCAGGCUGAUGAGXCGAAAUCCGGUC2949GACCGGATTCCTGGTGC2039HS GATA6PR 1254CGCACCAGCUGAUGAGXCGAAAAUCCGGU2950ACCGGATTCCTGGTGCG2940HS GATA6PR 1255CCGCGGCGCUGAUGAGXCGAAAGCCCUCC2951GGAGGGCTCCGCCGCGG2095HS GATA6PR 1256AGUGGAGUCUGAUGAGXCGAAAGGCCCGC2952GCGGGCCTCACTCCACT2108HS GATA6PR 1256AGUGGAGUCUGAUGAGXCGAAAGGCCCGC2953GCCTCACTCCACTOGTG2112HS GATA6PR 1258GCAGACACCUGAUGAGXCGAAAGUGGAGU2954ACTCCACTCGTGTCTGC2117HS GATA6PR 1259CAAAAGCACUGAUGAGXCGAAACACGAGU2955ACTOGTGTCTGCTTTTG2122HS GATA6PR 1260CUGCACAACUGAUGAGXCGAAAGCAGACA2956TGTCTGCTTTTGTGCAC2127HS GATA6PR 1261GCUGCACACUGAUGAGXCGAAAAGCAGAC2957GTCTGCTTTTGTGCAGC2128HS GATA6PR 1262UGCUGCACCUGAUGAGXCGAAAAAGCAGA2958TCTGCTTTTGTGCAGCA2129HS GATA6PR 1263ACUGUCUGCUGAUGAGXCGAAACUGCUGC2959GCAGCAGTCCAGACAGT2140HS GATA6PR 1264GGCACGAGCUGAUGAGXCGAAAUCACGUU2960AACGTGATTCTCGTGCC2174HS GATA6PR 1265AGGCACGACUGAUGAGXCGAAAAUCACGU2961ACGTGATTCTCGTGCCT2175HS GATA6PR 1266AAAGGCACCUGAUGAGXCGAAAGAAUCAC2962GTGATTCTCGTGCCTTT2177HS GATA6PR 1267UCAAAAUACUGAUGAGXCGAAAGGCACGA2963TCGTGCCTTTATTTTGA2184HS GATA6PR 1268UUCAAAAUCUGAUGAGXCGAAAAGGCACG2064CGTGCCTTTATTTTGGA2185HS GATA6PR 1269UUUCAAAACUGAUGAGXCGAAAAAGGCAC2965GTGCCTTTATTTTGAAA2186HS GATA6PR 1270UCUUUCAACUGAUGAGXCGAAAUAAAGGC2966GCCTTTATTTTGAAAGA2188HS GATA6PR 1271CUCUUUCACUGAUGAGXCGAAAAUAAAGG2967CCTTTATTTTGAAAGAG2189HS GATA6PR 1272UCUCUUUCCUGAUGAGXCGAAAAAUAAAG2968CTTTATTTTGAAAGAGA2190HS GATA6PR 2202 UUGGGAAACUGAUGAGXCGAAACAUCUCU2969AGAGATGTTTTTCCCAA1273 1274CUUGGGAACUGAUGAGXCGAAAACAUCUC2970GAGATGTTTTTCCCAAG2203HS GATA6PR i ante iii. Flammerhead ribozymes targeting GATA transcription factors (1.2,3,4, and 6) and the complementary sequences 1275UCUUGGGACUGAUGAGXCGAAAAACAUCU2971AGATGTTTTTCCCAAGA2204HS GATA6PR 1276CUCUUGGGCUGAUGAGXCGAAAAAACAUC2972GATGTTTTTCCCAAGAG2205HS GATA6PR 1277CCUCUUGGCUGAUGAGXCGAAAAAAACAU2973ATGTTTTTCCCAAGAGG2206HS GATA6PR 1278CUUUCAGCCUGAUGAGXCGAAAGCCUCUU2974AAGAGGCTTCCTGAAAG2217HS GATA6PR 1279AGUGGCCCCUGAUGAGXCGAAAGCGCCCA2975TGGGCGCTTGGGCCACT2269HS GATA6PR 1280GCUGGCUGCUGAUGAGXCGAAAGUGGCCC2976GGGCCACTCCAGCCAGC2278HS GATA6PR 1281CCGCCCCGCUGAUGAGXCGAAAGGCGGGC2977GCCCGCCTCCGGGGCGG2293HS GATA6PR 1282UGGAAGUGCUGAUGAGXCGAAAGCAGGGU2978ACCCTGCTCCACTTCCA2310HS GATA6PR 1283GCUUCUGGCUGAUGAGXCGAAAGUGGAGC2979GCTCCACTTCCAGAAGC2315HS GATA6PR 1284GGCUUCUGCUGAUGAGXCGAAAAGUGGAG2980CTCCACTTCCAGAAGCC2316HS GATA6PR 1285CCAGGUCCCUGAUGAGXCGAAAGUCCUGG2981CCAGGACTAGGACCTGG2331HS GATA6PR 1286UAGCAGGCCUGAUGAGXCGAAAGGCCCAG2982CTGGGCCTTGCCTGCTA2344HS GATA6PR 1287AUAUUCCACUGAUGAGXCGAAAGCAGGCA2983TGCCTGCTATGGAATAT2352HS GATA6PR 1288UCUCUCAACUGAUGAGXCGAAAUUCCAUA2984TATGGAATATTGAGAGA2359HS GATA6PR 2361 UCUCUCUCCUGAUGAGXCGAAAUAUUCCA2985TGGAATATTGAGAGAGA1289 1290UUUUAAAACUGAUGAGXCGAAAUCUCUCU2986AGAGAGATTTTTTAAAA2371HS GATA6PR 1291UUUUUAAACUGAUGAGXCGAAAAUCUCUC2987GAGAGATTTTTTAAAAA2372HS GATA6PR 1292UUUUUUAACUGAUGAGXCGAAAAAUCUCU2988AGAGATTTTTTAAAAAA2373HS GATA6PR 1293CUUUUUUACUGAUGAGXCGAAAAAAUCUC2989GAGATTTTTTAAAAAAG2374HS GATA6PR 2375 UCUUUUUUCUGAUGAGXCGAAAAAAAUCU2990AGATTTTTTAAAAAAGA1294 1295AUCUUUUUCUGAUGAGXCGAAAAAAAAUC2991GATTTTTTAAAAAAGAT2376HS GATA6PR 1296AAAUGCAACUGAUGAGXCGAAAUCUUUUU2992AAAAAGATTTTGCATTT2385HS GATA6PR 1297AAAAUGCACUGAUGAGXCGAAAACCUUUU2993AAAAGATTTTGCATTTT2386HS GATA6PR 1298CAAAAUGCCUGAUGAGXCGAAAAAUCUUU2994AAAGATTTTGCATTTTG2387HS GATA6PR 1299UUGGACAACUGAUGAGXCGAAAUGCAAAA2995TTTTGCATTTTGTCCAA2392HS GATA6PR 1300UUUGGACACOGAUGAGXCGAAAAUGCAAA2996TTTGCATTTTGTCCAAA2393HS GATA6PR 1301UUUUGGACCUGAUGAGXCGAAAAAUGCAA2997TTGCATTTTGTCCAAAA2394HS GATA6PR 1302UGAUUUUGCUGAUGAGXCGAAACAAAAUG2998CATTTTGTCCAAAATCA2397HS GATA6PR 1303AAGCACAUCUGAUGAGXCGAAAUUUUGGA2999TCCAAAATCATGTGCTT2404HS GATA6PR 2412 HSGATA6PR 1304AUCAGAAG CGAAAGCACACG3000CATGTGCTTCTTCTGATX 1305GADCAGAACUGAUGAGXCGAAAAGCACAU3001ATGTGCTTCTTCTGRTC2413HS GATA6PR 1306UUGAUCAGCUGAUGAGXCGAAAGAAGCAC3002GTGCTTCTTCTGATCAA2415HS GATA6PR 1307AUUGAUCACUGAUGAGXCGAAAAGAAGCA3003TGCTTCTTCTGATCAAT2416HS GATA6PR 1308CCAAAAUUCUGAUGAGXCGAAAUCAGAAG3004CTTCTGATCAATTTTGG2421HS GATA6PR 1309ACAACCAACUGAUGAGXCGAAAUUGAUCA3005TGATCAATTTTGGTTGT2425HS GATA6PR 1310AACAACCACUGAUGAGXCGAAAAUUGAUC3006GATCAATTTTGGTTGTT2426HS GATA6PR 1311GAACAACCCUGAUGAGXCGAAAAAUUGAU3007ATCAATTTTGGTTGTTC2427HS GATA6PR 1312UCUGGAACCUGAUGAGXCGAAACCAAAAU3008ATTTTGGTTGTTCCAGA2431HS GATA6PR 1313AAUUCUGGCUGAUGAGXCGAAACAACCAA3009TTGGTTGTTCCAGAATT2434HS GATA6PR 1314AAAUUCUGCUGAUGAGXCGAAAACAACCA3010TGGTTGTTCCAGAATTT2435HS GATA6PR 1315UAUGAAGACUGAUGAGXCGAAAUUCUGGA3011TCCAGAATTTCTTCATA2442HS GATA6PR 2443 GUAUGAAGCUGAUGAGXCGAAAAUUCUGG3012CCAGAATTTCTTCATAC1316 1317GGUAUGAACUGAUGAGXCGAAAAAUUCUG3013CAGAATTTCTTCATACC2444HS GATA6PR 1318AAGGUAUGCUGAUGAGXCGAAAGAAAUUC3014GAATTTCTTCATACCTT2446HS GATA6PR Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1319AAAGGUAUCUGAUGAGXCGAAAAGAAAUU3015AATTTCTTCATACCTTT2447HS GATA6PR 1320GGAAAAGGCUGAUGAGXCGAAAUGAAGAA3016TTCTTCATACCTTTTCC2450HS GATA6PR 1321AUGUGGAACUGAUGAGXCGAAAGGUAUGA3017TCATACCTTTTCCACAT2454HS GATA6PR 1322GAUGUGGACUGAUGAGXCGAAAAGGUAUG3018CATACCTTTTCCACATC2455HS GATA6PR 1323GGAUGUGGCUGAUGAGXCGAAAAAGGUAU3019ATACCTTTTCCACATCC2456HS GATA6PR 1324UGGAUGUGCUGAUGAGXCGAAAAAAGGUA3020TACCTTTTCCACATCCA2457HS GATA6PR 1325GAAAUCUGCUGAUGAGXCGAAAUGUGGAA3021TTCCACATCCAGATTTC2463HS GATA6PR 1326GCACAUGACUGAUGAGXCGAAAUCUGGAU3022ATCCAGATTTCATGTGC2469HS GATA6PR 1327CGCACAUGCUGAUGAGXCGAAAAUCUGGA3023TCCAGATTTCATGTGCG2470HS GATA6PR 1328ACGCACAUCUGAUGAGXCGAAAAAUCUGG3024CCAGATTTCATGTGCGT2471HS GATA6PR 1329UCUCCAUGCUGAUGAGXCGAAACGCACAU3025ATGTGCGTTCATGGAGA2480HS GATA6PR 1330UUCUCCAUCUGAUGAGXCGAAAACGCACA3026TGTGCGTTCATGGAGAA2481HS GATA6PR 1331CCUCAAGUCUGAUGAGXCGAAAUCUUCUC3027GAGAAGATCACTTGAGG2493HS GATA6PR 1332AUGGCCUCCUGAUGAGXCGAAAGUGAUCU3028AGATCACTTGAGGCCAT2497HS GATA6PR 1333GUGUACCACUGAUGAGXCGAAAUGGCCUC3029GAGGCCATTTGGTACAC2506HS GATA6PR 1334UGUGUACCCUGAUGAGXCGAAAAUGGCCU3030AGGCCATTTGGTACACA2507HS GATA6PR 2511 HSGATA6PR 1335 GAGAUGUG CUGAUGAG X CGAA ACCAAAUG 3031 CATTTGGT A CACATCTC 1336CCUCCAGACUGAUGAGXCGAAAUGUGUAC3032GTACACATCTCTGGAGG2517HS GATA6PR 1337AGCCUCCACUGAUGAGXCGAAAGAUGUGU3033ACACATCTCTGGAGGCT2519HS GATA6PR 1338CAUGAACCCUGAUGAGXCGAAACUCAGCC3034GGCTGAGTCGGTTCATG3532HS GATA6PR 2536 HSGATA6PR 1339 ACCUCAUG CUGAUGAG X CGAA ACCGACUC 3035 GAGTCGGT T CATGAGGT 2537 HSGATA6PR 1340 GACCUCAU CUGAUGAG X CGAA AACCGACU 3036 AGTCGGTT C ATGAGGTC 2545 HSGATA6PR 1341 UGAUAAGA CUGAUGAG X CGAA ACCUCAUG 3037 CATGAGGT C TCTTATCA 2547 HSGATA6PR 1342 UUUGAUAA CUGAUGAG X CGAA AGACCUCA 3038 TGAGGTCT C TTATCAAA 2549 HSGATA6PR 1343 UUUUUGAU CUGAUGAG X CGAA AGAGACCU 3039 AGGTCTCT T ATCAAAAA 2550 HSGATA6PR 1344 AUUUUUGA CUGAUGAG X CGAA AAGAGACC 3040 GGTCTCTT A TCAAAAAT 2552 HSGATA6PR 1345 AUAUUUUU CUGAUGAG X CGAA AUAAGAGA 3041 TCTCTTAT C AAAAATAT 2559 HSGATA6PR 1346 CUGAGUAA CUGAUGAG X CGAA AUUUUUGA 3042 TCAAAAAT A TTACTCAG 2561 HSGATA6PR 1347 AACUGAGU CUGAUGAG X CGAA AUAUUUUU 3043 AAAAATAT T ACTCAGTT 2562 HSGATA6PR 1348 AAACUGAG CUGAUGAG X CGAA AAUAUUUU 3044 AAAATATT A CTCAGTTT 2565 HSGATA6PR 1349 UGCAAACU CUGAUGAG X CGAA AGUAAUPU 3045 ATATTACT C AGTTTGCA 2569 HSGATA6PR 1350 GUCUUGCA CUGAUGAG X CGAA ACUGAGUA 3046 TACTCAGT T TGCAAGAC 2570 HSGATA6PR 1351 AGUCUUGC CUGAUGAG X CGAA AACUGAGU 3047 ACTCAGTT T GCAAGACT 2583 HSGATA6PR 1352 AAAGUUAC CUGAUGAG X CGAA AUGCAGUC 3048 GACTGCAT T GTAACTTT 2586 HSGATA6PR 1353 GUUAAAGU CUGAUGAG X CGAA ACAAUGCA 3049 TGCATTGT A ACTTTAAC 2590 HSGATA6PR 1354 GUAUGUUA CUGAUGAG X CGAA AGUUACAA 3050 TTGTAACT T TAACATAC 2591 HSGATA6PR 1355 UGUAUGUU CUGAUGAG X CGAA AAGUUACA 3051 TGTAACTT T AACATACA 2592 HSGATA6PR 1356 GUGUAUGU CUGAUGAG X CGAA AAAGUUAC 3052 GTAACTTT A ACATACAC 2597 HSGATA6PR 1357 UCACAGUG CUGAUGAG X CGAA AUGUUAAA 3053 TTTAACAT A CACTGTGA 2613 HSGATA6PR 1358 CUUUGAGA CUGAUGAG X CGAA ACGUCAGU 3054 ACTGACGT T TCTCAAAG 2614 HSGATA6PR 1359 ACUUUGAG CUGAUGAG X CGAA AACGUCAG 3055 CTGACGTT T CTCAAAGT 2615 HSGATA6PR 1360 AACUUUGA CUGAUGAG X CGAA AAACGUCA 3056 TGACGTTT C TCAAAGTT 2617 HSGATA6PR 1361 UGAACUUU CUGAUGAG X CGAA AGAAACGU 3057 ACGTTTCT C AAAGTTCA 2623 HSGATA6PR 1362 ACAAUAUG CUGAUGAG X CGAA ACUUCGAG 3058 CTCAAAGT T CATATTGT Table m. Hammerhead ribozymes targeting GATA transcription factors (1, X, 3,4, and 6) and the complementary sequences 1363CACAAUAUCUGAUGAGXCGAAAACUUUGA3059TCAAAGTTCATATTGIG2624HS GATA6PR 1364CCACACAACUGAUGAGXCGAAAUGAACUU3060AAGTTCATATTGTGTGG2627HS GATA6PR 1665AGCCACACCUGAUGAGXCGAAAUAUGAAC3061GTTCATATTGTGTGGCT2629HS GATA6PR 1366UGACUUCACUGAUGAGXCGAAAUCAGCCA3062TGGCTGATCTGAAGTCA2641HS GATA6PR 1367UUCCGACUCUGAUGAGXCGAAACUUCAGA3063TCTGAAGTCAGTCGGAA2648HS GATA6PR 1368CAAAUUCCCUGAUGAGXCGAAACUGACUU3064AAGTCAGTCGGAATTTG2652HS GATA6PR 1369UGUUUACACUGAUGAGXCGAAAUUCCGAC3065GTCGGAATTTGTAAACA2658HS GATA6PR 1370CUGUUUACCUGAUGAGXCGAAAAUUCCGA3066TCGGAATTTGTAAACAG2659HS GATA6PR 1371ACCCUGUUCUGAUGAGXCGAAACAAAUUC3067GAATTTGTAAACAGGGT2662HS GATA6PR 1372UUGUUUGGCUGAUGAGXCGAAACCCUGUU3068AACAGGGTACCAAACAA2671HS GATA6PR 1373AAGAAAAACUGAUGAGXCGAAAUCUUGUU3069AACAAGATATTTTTCTT2683HS GATA6PR 1374GGAAGAAACUGAUGAGXCGAAAUAUCUUG3070CAAGATATTTTTCTTCC2685HS GATA6PR 1375UGGAAGAACUGAUGAGXCGAAAAUAUCUU3071AAGATATTTTTCTTCCA2686HS GATA6PR 1376AUGGAAGACUGAUGAGXCGAAAAAUAUCU3072AGATATTTTTUTTCCAT2687HS GATA6PR 1377CAUGGAAGCUGAUGAGXCGAAAAAAUAUC3073GATATTTTTCTTCCATG2688HS GATA6PR 1378ACADGGAACUGAUGAG2689HSGATA6PR X 3074ATATTTTTCTTCCATGTAAAAAUAU 1379AUACAUGGCUGAUGAGXCGAAAGAAAAAU3075ATTTTTCTTCCATGTAT2691HS GATA6PR 1380UAUACAUGCUGAUGAGXCGAAAAGAAAAA3076TTTTTCTTCCATGTATA2692HS GATA6PR 1381UUAUUGUACUGAUGAGXCGAAACAUGGAA3077TTOCATGTATACAATAA2698HS GATA6PR 1382AAUUAUUGCUGAUGAGXCGAAAUACAUGG3078CCATGTATACAATAATT2700HS GATA6PR 1383AAAAAAAUCUGAUGAGXCGAAAUUGUAUA3079TATACAATAATTTTTTT2705HS GATA6PR 1384UUUAAAAACOGAUGAGXCGAAAUUAUUGU3080ACAATAATTTTTTTAAA2708HS GATA6PR 1385UUUUAAAACUGAUGAGXCGAAAAUUAUUG3081CAATAATTTTTTTAAAA2709HS GATA6PR 1386UUUUUAAACUGAUGAGXCGAAAAAUUAUU3082AATAATTTTTTTAAAAA2710HS GATA6PR 1387CUUUUUAACUGAUGAGXCGAAAAAAUUAU3083ATAATTTTTTTAAAAAG2711HS GATA6PR 1388ACUUUUUACUGAUGAGXCGAAAAAAAUUA3084TAATTTTTTTAAAAAGT2712HS GATA6PR 2713 CACUUUUUCUGAUGAGXCGAAAAAAAAUU3085AATTTTTTTAAAAAGTG1389 1390GCACUUUUCUGAUGAGXCGAAAAAAAAAU3086ATTTTTTTAAAAAGTGC2714HS GATA6PR 1391GCAACGCACUGAUGAGXCGAAAUUGCACU3087AGTGCAATTTGCGTTGC2726HS GATA6PR 1392UGCAACGCCUGAUGAGXCGAAAAUUGCAC3088GTGCAATTTGCGTTGCA2727HS GATA6PR 1393AUUGCUGCCUGAUGAGXCGAAACGCAAAU3089ATTTGCGTTGCAGCAAT2732HS GATA6PR 1394UUAACACUCUGAUGAGXCGAAAUUGCUGC3090GCAGCAATCAGTGTTAA2741HS GATA6PR 1395AADGAUUUCUGAUGAGXCGAAACACUGAU3091ATCAGTGTTAAATCATT2747HS GATA6PR 1396AAAUGAUUCUGAUGAGXCGAAAACACUGA3092TCAGTGTTAAATCATTT2748HS GATA6PR 1397AUGCAAAUCUGAUGAGXCGAAAUUUAACA3093TGTTAAATCATTTGCAT2752HS GATA6PR 1398CCUAUGCACUGAUGAGXCGAAAUGAUUUA3094TAAATCATTTGCATAGG2755HS GATA6PR 1399UCCUAUGCCUGAUGAGXCGAAAAUGAUUU3095AAATCATTTGCATAGGA2756HS GATA6PR 1400UUAAAUCCCUGAUGAGXCGAAAUGCAAAU3096ATTTGCATAGGATTTAA2761HS GATA6PR 1401UGCUGUUACUGAUGAGXCGAAAUCCUAUG3097CATAGGATTTAACAGCA2766HS GATA6PR 1402AUGCUGUUCUGAUGAGXCGAAAAUCCUAU3098ATAGGATTTAACAGCAT2767HS GATA6PR 1443AAUGCUGUCUGAUGAGXCGAAAAAUCCUA3099TAGGATTTAACAGCATT2768HS GATA6PR 1404UUAUAAAACUGAUGAGXCGAAAUGCUGUU3100AACAGCATTTTTTATAA2776HS GATA6PR 1405AUUAUAAACUGAUGAGXCGAAAAUGCUGU3101ACAGCATTTTTTATAAT2777HS GATA6PR 1406CAUUAUAACUGAUGAGXCGAAAAAUGCUG3102CAGCATTTTTTATAATG2778HS GATA6PR Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1407UCAUUAUACUGAUGAGXCGAAAAAAUGCU3103AGCATTTTTTATAATGA2779HS GATA6PR 1408UUCAUUAUCUGAUGAGXCGAAAAAAAUGC3104GCATTTTTTATAATGAA2780HS GATA6PR 1409AUUCAUUACUGAUGAGXCGAAAAAAAATG3105CATTTTTTATAATGAAT2781HS GATA6PR 1410ACAUUCAUCUGAUGAGXCGAAAUAAAAAA3106TTTTTTATAATGAATGT2783HS GATA6PR 1411AAAAUGUUCUGAUGAGXCGAAACAUUCAU3107ATGAATGTAAACATTTT2792HS GATA6PR 1412UAAGUUAACUGAUGAGXCGAAAUGUUUAC3108GTAAACATTTTAACTTA2798HS GATA6PR 1413UUAAGUUACUGAUGAGXCGAAAAUGUUUA3109TAAACATTTTAACTTAA2799HS GATA6PR 1414AUUAAGUUCUGAUGAGXCGAAAAAUGUUU3110AAACATTTTAACTTAAT2800HS GATA6PR 1415CAUUAAGUCUGAUGAGXCGAAAAAAUGUU3111AACATTTTAACTTAATG2801HS GATA6PR 1416GUACCAUUCUGAUGAGXCGAAAGUUAAAA3112TTTTAACTTAATGGTAC2805HS GATA6PR 1417AGUACCAUCUGAUGAGXCGAAAAGUUAAA3113TTTAACTTAATGGTACT2806HS GATA6PR 1418AUUUUAAGCUGAUGAGXCGAAACCAUUAA3114TTAATGGTACTTAAAAT2812HS GATA6PR 1419AUUAUUUUCUGAUGAGXCGAAAGUACCAU3115ATGGTACTTAAAATAAT2815HS GATA6PR 1420AAUUAUUUCUGAUGAGXCGAAAAGUACCA3116TGGTACTTAAAATAATT2816HS GATA6PR 1421UUUUAAAUCUGAUGAGXCGAAAUUUUAAG3117CTTAAAATAATTTAAAA2821HS GATA6PR 2824 HSGATA6PR 1422 UUCUUUUA CUGAUGAG X CGAA AUUAUUUU 3118 AAAATAAT T TAAAAGAA 2825 HSGATA6PR 1423 UUUCUUUU CUGAUGAG X CGAA AAUUAUUU 3119 AAATAATT T AAAAGAAA 2826 HSGATA6PR 1424 UUUUCUUU CUGAUGAG X CGAA AAAUUAUU 3120 AATAATTT A AAAGAAAA 2839 UCUAAGUUCUGAUGAGXCGAAACAUUUUU3121AAAAATGTTAACTTAGA1425 2840 HSGATA6PR 1426 GUCUAAGU CUGAUGAG X CGAA AACAUUUU 3122 AAAATGTT A ACTTAGAC 1427GAAUGUUUCUGAUGAGXCGAAAGUUAACA3123TGTTAACTTAGACATTC2844HS GATA6PR 2845 HSGATA6PR 1428 AGAAUGUC CUGAUGAG X CGAA AAGUUAAC 3124 GTTAACTT A GACATTCC 2851 HSGATA6PR 1429 AGCAUAAG CUGAUGAG X CGAA AUGUCUAA 3125 TTAGACAT T CTTATGCT 2852 HSGATA6PR 1430 AAGCAUAA CUGAUGAG X CGAA AAUGUCUA 3126 TAGACATT C TTATGCTT 2854 HSGATA6PR 1431 AGAAGCAU CUGAUGAG X CGAA AGAAUGUC 3127 GACATTCT T ATGCTTCT 2855 HSGATA6PR 1432 AAGAAGCA CUGAUGAG X CGAA AAGAAUGU 3128 ACATTCTT A TGCTTCTT 2860 HSGATA6PR 1433 UGUAAAAG CUGAUGAG X CGAA AGCAUAAG 3129 CTTATGCT T CTTTTACA 2861 HSGATA6PR 1434 UUGUAAAA CUGAUGAG X CGAA AAGCAUAA 3130 TTATGCTT C TTTTACAA 2863 HSGATA6PR 1435 AGUUGUAA CUGAUGAG X CGAA AGAAGCAU 3131 ATGCTTCT T TTACAACT 2864 HSGATA6PR 1436 UAGUUGUA CUGAUGAG X CGAA AAGAAGCA 3132 TGCTTCTT T TACAACTA 2865 HSGATA6PR 1437 GUAGUUGU CUGAUGAG X CGAA AAAGAAGC 3133 GCTTCTTT T ACAACTAC 2866 HSGATA6PR 1438 UGUAGUUG CUGAUGAG X CGAA AAAAGAAG 3134 CTTCTTTT A CAACTACA 2872 HSGATA6PR 1439 AUGGGAUG CUGAUGAG X CGAA AGUUGUAA 3135 TTACAACT A CATCCCAT 2876 HSGATA6PR 1440 UAAAAUGG CUGAUGAG X CGAA AUGUAGUU 3136 AACTACAT C CCATTTTA 2881 HSGATA6PR 1441 AAAUAUAA CUGAUGAG X CGAA AUGGGAUG 3137 CATCCCAT T TTATATTT 2882 HSGATA6PR 1442 GAAAUAUA CUGAUGAG X CGAA AAUGGGAU 3138 ATCCCATT T TATATTTC 2883 HSGATA6PR 1443 GGAAAUAU CUGAUGAG X CGAA AAAUGGGA 3139 TCCCATTT T ATATTTCC 2884 HSGATA6PR 1444 UGGAAAUA CUGAUGAG X CGAA AAAAUGGG 3140 CCCATTTT A TATTTCCA 2886 HSGATA6PR 1445 AUUGGAAA CUGAUGAG X CGAA AUAAAAUG 3141 CATTTTAT A TTTCCAAT 2888 HSGATA6PR 1446 CAAUUGGA CUGAUGAG X CGAA AUAUAAAA 3142 TTTTATAT T TCCAATTG 2889 HSGATA6PR 1447 ACAAUUGG CUGAUGAG X CGAA AAUAUAAA 3143 TTTATATT T CCAATTGT 2890 HSGATA6PR 1448 AACAAUUG CUGAUGAG X CGAA AAAUAUAA 3144 TTATATTT C CAATTGTT 2895 HSGATA6PR 1449 UCUUUAAC CUGAUGAG X CGAA AUUGGAAA 3145 TTTCCAAT T GTTAAAGA 2898 HSGATA6PR 1450 UUUUCUUU CUGAUGAG X CGAA ACAAUUGG 3146 CCAATTGT T AAAGAAAA Table m. Hammerhead ribozymes targeting GATA transcription factors 4, and 6) and the complementary sequences 1451UUUUUCUUCUGAUGAGXCGAAAACAAUUG3147CAATTGTTAAAGAAAAA2899HS GATA6PR 1452UCUUGAAACUGAUGAGXCGAAAUUUUUCU3148AGAAAAATATTTCAAGA2909HS GATA6PR 1453GUUCUUGACUGAUGAGXCGAAAUAUUUUU3149AAAAATATTTCAAGAAC2911HS GATA6PR 1454UGUUCUUGCUGAUGAGXCGAAAAUAUUUU3150AAAATATTTCAAGAACA2912HS GATA6PR 1455UUGUUCUUCUGAUGAGXCGAAAAAUAUUU3151AAATATTTCAAGAACAA2913HS GATA6PR 1456UGAGAGAACUGAUGAGXCGAAAUUUGUUC3152GAACAAATCTTCTCTCA2924HS GATA6PR 1457CCUGAGAGCUGAUGAGXCGAAAGAUUUGU3153ACAAATCTTCTCTCAGG2926HS GATA6PR 1458UCCUGAGACUGAUGAGXCGAAAAGAUUUG3154CAAATCTTCTCTCAGGA2927HS GATA6PR 1459UUUCCUGACUGAUGAGXCGAAAGAAGAUU3155AATCTTCTCTCAGGAAA2929HS GATA6PR 1460AUUUUCCUCUGAUGAGXCGAAAGAGAAGA3156TCTTCTCTCAGGAAAAT2931HS GATA6PR 1461AGAAAGGCCUGAUGAGXCGAAAUUUUCCU3157AGGAAAATTGCCTTTCT2940HS GATA6PR 1462AAUAGAGACUGAUGAGXCGAAAGGCAAUU3158AATTGCCTTTCTCTATT2945HS GATA6PR 2946 HSGATA6PR 1463 AAAUAGAG CUGAUGAG X CGAA AAGGCAAU 3159 ATTGCCTT T CTCTRTTT 2947 HSGATA6PR 1464 CAAAUAGA CUGAUGAG X CGAA AAAGGCAA 3160 TTGCCTTT C TCTATTTG 1465AACAAAUACUGAUGAGXCGAAAGAAAGGC3161GCCTTTCTCTATTTGTT2949HS GATA6PR 1466UUAACAAACUGAUGAGXCGAAAGAGAAAG3162CTTTCTCTATTTGTTAA2951HS GATA6PR 1467UCUUAACACUGAUGAGXCGAAAUAGAGAA3163TTCTCTATTTGTTAAGA2953HS GATA6PR 1468UUCUUAACCUGAUGAGXCGAAAAUAGAGA3164TCTCTATTTGTTAACAA2954HS GATA6PR 1469AAAUUCUUCUGAUGAG2957HSGATA6PR X 3165CTATTTGTTAAGAATTTACAAAUAG 1470AAAAUUCUCUGAUGAGXCGAAAACAAAUA3166TATTTGTTAAGAATTTT2958HS GATA6PR 1471UGUAUAAACUGAUGAGXCGAAAUUCUUAA3167TTAAGAATTTTTATACA2964HS GATA6PR 1472UUGUAUAACUGAUGAGXCGAAAAUUCUUA3168TAAGAATTTTTATACAA2965HS GATA6PR 2966 HSGATA6PR 1473 CUUGUAUA CUGAUGAG X CGAA AAAUUCUU 3169 AAGAATTT T TATACAAG 2967 HSGATA6PR 1474 UCUUGUAU CUGAUGAG X CGAA AAAAUUCU 3170 AGAATTTT T ATACAAGA 2968 HSGATA6PR 1475 UUCUUGUA CUGAUGAG X CGAA AAAAAUUC 3171 GAATTTTT A TACAAGAA 2970 HSGATA6PR 1476 UGUUCUUG CUGAUGAG X CGAA AUAAAAAU 3172 ATTTTTAT A CAAGAACA 2984 HSGATA6PR 1477 AGGGGGUA CUGAUGAG X CGAA AUUGGUGU 3173 ACACCAAT A TACCCCCT 2986 HSGATA6PR 1478 AAAGGGGG CUGAUGAG X CGAA AUAUUGGU 3174 ACCAATAT A CCCCCTTT 2993 HSGATA6PR 1479 GUAAAAUA CUGAUGAG X CGAA AGGGGGUA 3175 TACCCCCT T TATTTTAC 2994 HSGATA6PR 1480 AGUAAAAU CUGAUGAG X CGAA AAGGGGGU 3176 ACCCCCTT T ATTTTACT 2995 HSGATA6PR 1481 CAGUAAAA CUGAUGAG X CGAA AAAGGGGG 3177 CCCCCTTT A TTTTACTG 2997 HSGATA6PR 1482 CACAGUAA CUGAUGAG X CGAA AUAAAGGG 3178 CCCTTTAT T TTACTGTG 2998 HSGATA6PR 1483 CCACAGUA CUGAUGAG X CGAA AAUAAAGG 3179 CCTTTATT T TACTGTGG 2999 HSGATA6PR 1484 UCCACAGU CUGAUGAG X CGAA AAAUAAAG 3180 CTTTATTT T ACTGTGGA 3000 HSGATA6PR 1485 UUCCACAG CUGAUGAG X CGAA AAAAUAAA 3181 TTTATTTT A CTGTGGAA 3010 HSGATA6PR 1486 CCAGCACA CUGAUGAG X CGAA AUUCCACA 3182 TGTGGAAT A TGTGCTGG 3025 HSGATA6PR 1487 GUUGUUGC CUGAUGAG X CGAA AUUUUUCC 3183 GGAAAAAT T GCAACAAC 3037 HSGATA6PR 1488 AGGUAGUA CUGAUGAG X CGAA AGUGUUGU 3184 ACAACACT T TACTACCT 3038 HSGATA6PR 1489 UAGGUAGU CUGAUGAG X CGAA AAGUGUUG 3185 CAACACTT T ACTACCTA 3039 HSGATA6PR 1490 UUAGGUAG CDGAUGAG X CGAA AAAGUGUU 3186 AACACTTT A CTACCTAA 3042 HSGATA6PR 1491 CCGUUAGG CUGAUGAG X CGAA AGUAAAGU 3187 ACTTTACT A CCTAACGG 3046 HSGATA6PR 1492 CUAUCCGU CUGAUGAG X CGAA AGGUAGUA 3188 TACTACCT A ACGGATAG 3053 HSGATA6PR 1493 ACAAAUGC CUGAUGAG X CGAA AUCCGUUA 3189 TAACGGAT A GCATTTGT 3058 HSGATA6PR 1494 UAUUUACA CUGAUGAG X CGAA AUGCUAUC 3190 GATAGCAT T TGTAAATA Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1495GUAUUUACCUAGUCAGXCGAAAAUGCUAU3191ATAGCATTTGTAAATAC3059HS GATA6PR 1496AGAGUAUUCUGAUGAGXCGAAACAAALIC3192GCATTTGTAAATACTCT3062HS GATA6PR 1497ACCUAGAGCUGAUGAGXCGAAAUUUACAA3193TTGTAAATACTCTAGGT3066HS GATA6PR 1498GAUACCUACUGAUGAGXCGAAAGUAUUUA3194TAAATACTCTAGGTATC3069HS GATA6PR 1499CAGAUACCCUGAUGAGXCGAAAGAGUAUU3195AATACTCTAGGTATCTG3071HS GATA6PR 3075 UUUACAGACUGAUGAGXCGAAAOCUAGAG3196CTCTAGGTATCTGTAAA1500 1501UGUUUACACUGAUGAGXCGAAAUACCUAG3197CTAGGTATCTGTAAACA3077HS GATA6PR 1502AGAGUGUUCUGAUGAGXCGAAACAGAUAC3198GTATCTGTAAACACTCT3081HS GATA6PR 1503CUUCAUCACUGAUGAGXCGAAAGUGUUUA3199GATGAAGTCTGATGAAG3088HS GATA6PR 1504ACUAUACACUGAUGAGXCGAAACCUCAUC3200GATGAAGTCTGTATAGT3098HS GATA6PR 1505UCACACUACUGAUGAGXCGAAACAGACUU3201AAGTCTGTATAGTGIGA3102HS GATA6PR 3104 HSGATA6PR 1506 AGUCACAC CUGAUGAG X CGAA AUACAGAC 3202 GTCTGTAT A GTGIGACT 3113 HSGATA6PR 1507 CUGUGGGU CUGAUGAG X CGAA AGUCACAC 3203 GTGTGACT A ACCCACAG 3128 HSGATA6PR 1508 UGUAAACC CUGAUGAG X CGAA ACCUGCCU 3204 AGGCAGGT T GGTTTACA 3132 HSGATA6PR 1509 UUAAUGUA CUGAUGAG X CGAA ACCAACCU 3205 AGGTTGGT T TACATTAA 1510AUUAAUGUCUGAUGAGXCGAAAACCAACC3206GGTTGGTTTACATTAAT3133HS GATA6PR 1511AAUUAAUGCUGAUGAGXCGAAAAACCAAC3207GTTGGTTTACATTAATT3134HS GATA6PR 1512AAAAAAUUCUGAUGAGXCGAAAUGUAAAC3208GTTTACATTAATTTTTT3138HS GATA6PR 1513AAAAAAAUCUGAUGAGXCGAAAAUGUAAA3209TTTACATTAATTTTTTT3139HS GATA6PR 1514AAAAAAAACUGAUGAGXCGAAAUUAAUGU3210ACATTAATTTTTTTTTT3142HS GATA6PR 1515AAAAAAAACUGAUGAGXCGAAAAUUAAUG3211CATTAATTTTTTTTTTT3143HS GATA6PR 3144 HSGATA6PR 1516 CAAAAAAA CUGAUGAG X CGAA AAAUUAAU 3212 ATTAATTT T TTTTTTTT 3145 HSGATA6PR 1517 UCAAAAAA CUGAUGAG X CGAA AAAAUUAA 3213 TTAATTTT T TTTTTTGA 3146 HSGATA6PR 1518 UUCAAAAA CUGAUGAG X CGAA AAAAAUUA 3214 TAATTTTT T TTTTTGAA 3147 HSGATA6PR 1519 AUUCAAAA CUGAUGAG X CGAA AAAAAAUU 3215 AATTTTTT T TTTTGAAT 3148 HSGATA6PR 1520 CAUUCAAA CUGAUGAG X CGAA AAAAAAAU 3216 ATTTTTTT T TTTGAATG 3149 HSGATA6PR 1521 CCAUUCAA CUGAUGAG X CGAA AAAAAAAA 3217 TTTTTTTT T TTGAATGG 3150 HSGATA6PR 1522 CCCAUUCA CUGAUGAG X CGAA AAAAAAAA 3218 TTTTTTTT T TGAATGGG 3151 HSGATA6PR 1523 UCCCAUUC CUGAUGAG X CGAA AAAAAAAA 3219 TTTTTTTT T GAATGGGA 3163 HSGATA6PR 1524 UUCCAUAG CUGAUGAG X CGAA ACAUCCCA 3220 TGGGATGT C CTATGGAA 3166 HSGATA6PR 1525 GGUUUCCA CUGAUGAG X CGAA AGGACAUC 3221 GATGTCCT A TGGAAACC 3176 HSGATA6PR 1526 UGGUGAAA CUGAUGAG X CGAA AGGUUUCC 3222 GGAAACCT A TTTCACCA 3178 HSGATA6PR 1527 UCUGGUGA CUGAUGAG X CGAA AUAGGUUU 3223 AAACCTAT T TCACCAGA 3179 HSGATA6PR 1528 CUCUGGUG CUGAUGAG X CGAA AAUAGGUU 3224 AACCTATT T CACCAGAG 3180 HSGATA6PR 1529 ACUCUGGU CUGAUGAG X CGAA AAAUAGGU 3225 ACCTATTT C ACCAGAGT 3189 HSGATA6PR 1530 AUUUUUAA CUGAUGAG X CGAA ACUCUGGU 3226 ACCAGAGT T TTAAAAAT 3190 HSGATA6PR 1531 UAUUUUUA CUGAUGAG X CGAA AACUCUGG 3227 CCAGAGTT T TAAAAAAA 3291 HSGATA6PR 1532 UUAUUUUU CUGAUGAG X CGAA AAACUCUG 3228 CAGAGTTT T AAAAAAAA 3292 HSGATA6PR 1533 UUUAUUUU CUGAUGAG X CGAA AAAACUCU 3229 AGAGTTTT A AAAAAAAA 3198 HSGATA6PR 1534 ACCCUUUU CUGAUGAG X CGAA AUUUUUAA 3230 TTAAAAAT A AAAAAGGT 3207 HSGATA6PR 1535 CAAAACAA CUGAUGAG X CGAA ACCCCCCC 3231 AAAAGGGT A TTGTTTTG 3209 HSGATA6PR 1536 GACAAAAC CUGAUGAG X CGAA AUACCCUU 3232 AAGGGTAT T GTTTTGTC 3212 HSGATA6PR 1537 GAAGACAA CUGAUGAG X CGAA ACAAUACC 3233 GGTATTGT T TTGTCTTC 3213 HSGATA6PR 1538 AGAAGACA CUGAUGAG X CGAA AACAAUAC 3234 GTATTGTT T TGTCTTCT Table III. Hammerhead ribozymes targeting GATA transcription factors 4, and 6) and the complementary sequences 1539CAGAAGACCUGAUGAGXCGAAAAACAAUA3235TATTGTTTTGTCTTCTG3214HS GATA6PR 1540GUACAGAACUGAUGAGXCGAAACAAAACA3236TGTTTTGTTTTCTGTAC3217HS GATA6PR 1541CUGUACAGCUGAUGAGXCGAAAGACAAAA3237TTTTGTCTTCTGTACAG3219HS GATA6PR 1542ACUGUACACUGAUGAGXCGAAAAGACAAA3238TTTGTCTTCTGTACAGT3220HS GATA6PR 1543ACUCACUGCUGAUGAGXCGAAACAGAAGA3239TCTTCTGTACAGTGAGT3224HS GATA6PR 1544AGGGAAGGCUGAUGAGXCGAAACUCACUG3240CAGTGAGTTCCTTCCCT3233HS GATA6PR 1545AAGGGAAGCUGAUGAGXCGAAAACUCACU3241AGTGAGTTCCTTCCCTT3234HS GATA6PR 1546GAAAAGGGCUGAUGAGXCGAAAGGAACUC3242GAGTTCCTTCCCTTTTC3237HS GATA6PR 1547UGAAAAGGCUGAUGAGXCGAAAAGGAACU3243AGTTCCTTCCCTTTTCA3238HS GATA6PR 1548GCUUUGAACUGAUGAGXCGAAAGGGAAGG3244CCTTCCCTTTTCAAAGC3242HS GATA6PR 1549AGCUUUGACUGAUGAGXCGAAAAGGGAAG3245CTTCCCTTTTCAAAGCT3243HS GATA6PR 1550AAGCUUUGCUGAUGAGXCGAAAAAGGGAA3246TTCCCTTTTCAAAGCTT3244HS GATA6PR 1551AAAGCUUUCUGAUGAGXCGAAAAAAGGGA3247TCCCTTTTCAAAGCTTT3245HS GATA6PR 1552UAAAAAGACUGAUGAGXCGAAAGCUUUGA3248TCAAAGCTTTCTTTTTA3252HS GATA6PR 3253 HSGATA6PR 1553 AUAAAAAG CUGAUGAG X CGAA AAGCUUUG 3249 CAAAGCTT T CTTTTTAT 3254 HSGATA6PR 1554 CAUAAAAA CUGAUGAG X CGAA AAAGCUUU 3250 AGGCTTTT C TTTTTATG 3256 HSGATA6PR 1555 AGCAUAAA CUGAUGAG X CGAA AGAAAGCU 3251 AGCTTTCT T TTTATGCT 1556CAGCAUAACUGAUGAGXCGAAAAGAAAGC3252GCTTTCTTTTTATGCTG3257HS GATA6PR 1557ACAGCAUACUGAUGAGXCGAAAAAGAAAG3253CTTTCTTTTTATGCTGT3258HS GATA6PR 1558UACAGCAUCUGAUGAGXCGAAAAAAGAAA3254TTTCTTTTTATGCTGTA3259HS GATA6PR 1559AUACAGCACUGAUGAGXCGAAAAAAAGAA3255TTCTTTTTATGCTGTAT3260HS GATA6PR 32673267HSGATA6PR 1560 XCGAAACAGCAUA3256TATGCTGTATGIGACTACUGAUGAG 3275 HSGATA6PR 1561 AAUAUCUA CUGAUGAG X CGAA AGUCACAU 3257 ATGTGACT A TAGATATT 3277 HSGATA6PR 1562 UGAAUAUC CUGAUGAG X CGAA AUAGUCAC 3258 GTGACTAT A GATATTCA 3281 HSGATA6PR 1563 UAUAUGAA CUGAUGAG X CGAA AUCUAUAG 3259 CTATAGAT A TTCATATA 3283 HSGATA6PR 1564 UUUAUAUG CUGAUGAG X CGAA AUAUCUAU 3260 ATAGATAT T CATATAAA 3284 HSGATA6PR 1565 UUUUAUAU CUGAUGAG X CGAA AAUAUCUA 3261 TAGATATT C ATATAAAA 3287 HSGATA6PR 1566 UUGUUUUA CUGAUGAG X CGAA AUGAAUAU 3262 ATATTCAT A TAAAACAA 3289 HSGATA6PR 1567 ACUUGUUU CUGAUGAG X CGAA AUAUGAAU 3263 ATTCATAT A AAACAAGT 3309 HSGATA6PR 1568 AUUUUGCA CUGAUGAG X CGAA ACUUCACG 3264 CGTGAAGT T TGCAAAAT 3310 HSGATA6PR 1569 CAUUUUGC CUGAUGAG X CGAA AACUUCAC 3265 GTGAAGTT T GCAAAATG 3321 HSGATA6PR 1570 AGGCCCUA CUGAUGAG X CGAA AGCAUUUU 3266 AAAATGCT T TAAGGCCT 3322 HSGATA6PR 1571 AAGGCCUU CUGAUGAG X CGAA AAGCAUUU 3267 AAATGCTT T AAGGCCTT 3323 HSGATA6PR 1572 GAAGGCCU CUGAUGAG X CGAA AAAGCAUU 3268 AATGCTTT A AGGCCTTC 3330 HSGATA6PR 1573 UUGAAAGG CUGAUGAG X CGAA AGGCCUUA 3269 TAAGGCCT T CCTTTCAA 3331 HSGATA6PR 1574 UUUGAAAG CUGAUGAG X CGAA AAGGCCUU 3270 AAGGCCTT C CTTTCAAA 3334 HSGATA6PR 1575 UGCUUUGA CUGAUGAG X CGAA AGGAAGGC 3271 GCCTTCCT T TCAAAGCA 3335 HSGATA6PR 1576 AUGCUUUG CUGAUGAG X CGAA AAGGAAGG 3272 CCTTCCTT T CAAAGCAT 3336 HSGATA6PR 1577 UAUGCUUU CUGAUGAG X CGAA AAAGGAAG 3273 CTTCCTTT C AAAGCATA 3344 HSGATA6PR 1578 AAAAGGAC CUGAUGAG X CGAA AUGCUUUG 3274 CAAAGCAT A GTOCTTTT 3347 HSGATA6PR 1579 UCCAAAAG CUGAUGAX A CGAA ACUAUGCU 3275 AGCATAGT C CTTTTGGA 3350 HSGATA6PR 1580 GGCUUCAA CUGAUGAG X CGAA AGGACUAU 3276 ATAGTOCT T TTGGAGCT 3351 HSGATA6PR 1581 CGGCUCCA CUGAUGAG X CGAA AGGACUAU 3277 TAGTCCTT T TGGAGCCG 3352 HSGATA6PR 1582 ACGGCUCC CUGAUGAG X CGAA AAAGGACU 3278 AGTCCTTT T GGAGCCGT Table III. Hammerhead ribozymes targeting GATA transcription factors 4, and 6) and the complementary sequences 1583AGGUACCACUGAUGAGXCGAAACGGCUCC3279GGAGCCGTTTGGTACCT3361HS GATA6PR 1584AAGGUACCCUGAUGAGXCGAAAACGGCUC3280GAGCCGTTTGGTACCTT3362HS GATA6PR 1585AUAAAAGGCUGAUGAGXCGAAACCAAACG3281CGTTTGGTACCTTTTAT3366HS GATA6PR 1585AGGUAUAACUGAUGAGXCGAAAGGUACCA3282TGGTACCTTTTATACCT3370HS GATA6PR 1587AAGGUAUACUGAUGAGXCGAAAAGGUACC3283GGTACCTTTTATACCTT3371HS GATA6PR 1588CAAGGUAUCUGAUGAGXCGAAAAAGGUAC3284GTACCTTTTATACCTTG3372HS GATA6PR 1589CCAAGGUACUGAUGAGXCGAAAAAAGGUA3285TACCTTTTATACCTTGG3373HS GATA6PR 1590AGCCAAGGCUGAUGAGXCGAAAUAAAAGG3286CCTTTTATACCTTGGCT3375HS GATA6PR 1591AAUAAGCCCUGAUGAGXCGAAAGGUAUAA3287TTATACCTTGGCTTATT3379HS GATA6PR 1592CUUCAAAUCUGAUGAGXCGAAAGCCAAGG3288CCTTGGCTTATTTGAAG3384HS GATA6PR 1593ACUUCAAACUGAUGAGXCGAAAAGCCAAG3289CTTGGCTTATTTGAAGT3385HS GATA6PR 1594CAACUUCACUGAUGAGXCGAAAUAAGCCA3290TGGCTTATTTGAAGTTG3387HS GATA6PR 1595UCAACUUCCUGAUGAGXCGAAAAUAAGCC3291GGCTTATTTGAAGTTGA3388HS GATA6PR 1596CAUGUGUCCUGAUGAGXCGAAACUUCAAA3292TTTGAAGTTGACACATG3394HS GATA6PR 1597UAGUAACUCUGAUGAGXCGAAACCCCAUG3293CATGGGGTTAGTTACTA3407HS GATA6PR 3408 HSGATA6PR 1598 GUAGUAAC CUGAUGAG X CGAA AACCCCAU 3294 ATGGGGTT A GTTACTAC 3411 HSGATA6PR 1599 AGAGUAGU CUGAUGAG X CGAA ACUAACCC 3295 GGGTTAGT T ACTACTCT 3412 HSGATA6PR 1600 GAGAGUAG CUGAUGAG X CGAA AACUAACC 3296 GGTTAGTT A CTACTCTC 3415 HSGATA6PR 1601 AUGGAGAG CUGAUGAG X CGAA AGUAACUA 3297 TAGTTACT A CTCTCCAT 3418 HSGATA6PR 1602 CACAUGGA CUGAUGAG X CGAA AGUAGUAA 3298 TTACTACT C TCCATGIG 1603UGCACAUGCUGAUGAGXCGAAAGAGUAGU3299ACTACTCTCCATGTGCA3420HS GATA6PR 1604CUGUCCCCCUGAUGAGXCGAAAUGCACAU3300ATGTGCATTGGGGACAG3430HS GATA6PR 3440 HSGATA6PR 1605 CUUAUAAA CUGAUGAG X CGAA ACUGUCCC 3301 GGGACAGT T TTTATAAG 1606ACUUAUAACUGAUGAGXCGAAAACUGUCC3302GGACAGTTTTTATAAGT3441HS GATA6PR 3442 HSGATA6PR 1607 CACUUAUA CUGAUGAG X CGAA AAACUGUC 3303 GACAGTTT T TATAAGTG 3443 HSGATA6PR 1608 CCACUUAU CUGAUGAG X CGAA AAAACUGU 3304 ACAGTTTT T ATAAGTGG 3444 HSGATA6PR 1609 CCCACUUA CUGAUGAG X CGAA AAAAACUG 3305 CAGTTTTT A TAAGTGGG 3446 HSGATA6PR 1610 UUCCCACU CUGAUGAG X CGAA AUAAAAAC 3306 GTTTTTAT A AGTGGGAA 3460 HSGATA6PR 1611 AUAAUACU CUGAUGAG X CGAA AGUCCUUC 3307 GAAGGACT C AGTATTAT 3464 HSGATA6PR 1612 UAUAAUAA CUGAUGAG X CGAA ACUGAGUC 3308 GACTCAGT A TTATTATA 3466 HSGATA6PR 1613 AAUAUAAU CUGAUGAG X CGAA AUACUGAG 3309 CTCAGTAT T ATTATATT 3467 HSGATA6PR 1614 AAAUAUAA CUGAUGAG X CGAA AAUACUGA 3310 TCAGTATT A TTATATTT 3469 HSGATA6PR 1615 UCAAAUAU CUGAUGAG X CGAA AUAAUACU 3311 AGTATTAT T ATATTTGA 3470 HSGATA6PR 1616 CUCAAAUA CUGAUGAG X CGAA AAUAAUAC 3312 GTATTATT A TATTTGAG 3472 HSGATA6PR 1617 AUCUCAAA CUGAUGAG X CGAA AUAAUAAU 3313 ATTATTAT A TTTGAGAT 3474 HSGATA6PR 1618 UCAUCUCA CUGAUGAG X CGAA AUAUAAUA 3314 TATTATAT T TGAGATGA 3475 HSGATA6PR 1619 AUCAUCUC CUGAUGAG X CGAA AAUAUAAU 3315 ATTATATT T GAGATGAT 3484 HSGATA6PR 1620 AAAAUGCU CUGAUGAG X CGAA AUCAUCUC 3316 GAGATGAT A AGCATTTT 3490 HSGATA6PR 1621 CCAAACAA CUGAUGAG X CGAA AUGCUUAU 3317 ATAAGCAT T TTGTTTGG 3491 HSGATA6PR 1622 CCCAAACA CUGAUGAG X CGAA AAUGCUUA 3318 TAAGCATT T TGTTTGGG 3492 HSGATA6PR 1623 UCCCAAAC CUGAUGAG X CGAA AAAUGCUU 3319 AAGCATTT T GTTTGGGA 3495 HSGATA6PR 1624 UGUUCCCA CUGAUGAG X CGAA ACAAAAUG 3320 CATTTTGT T TGGGAACA 3496 HSGATA6PR 1625 UUGUUCCC CUGAUGAG X CGAA AACAAAAU 3321 ATTTTGTT T GGGAACAA 3509 HSGATA6PR 1626 AUAUUUUU CUGAUGAG X CGAA AGCAUUGU 3322 ACAATGCT T AAAAATAT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and 6) and the complementary sequences 1627AAUAUUUUCUGAUGAGXCGAAAAGCAUUG3323CAATGCTTAAAAATATT3510HS GATA6PR 1628UUCUGGAACUGAUGAGXCGAAAUUUUUAA3324TTAAAAATATTCCAGAA3516HS GATA6PR 1629CUUUCUGGCUGAUGAGXCGAAAUAUUUUU3325AAAAATATTCCAGAAAG3518HS GATA6PR 1630ACUUUCUGCUGAUGAXXCGAAAAUAUUUU3326AAAATATTCCAGAAAGT3519HS GATA6PR 1631AAAAUCUGCUGAUGAGXCGAAACUUUCUT3327CAGAAAGTTCAGATTTT3528HS GATA6PR 3529 AAAAAUCUCUGAUGAGXCGAAAACUUUCU3328GTTCAGATTTTTTTTCT1632 1633AGAAAAAACUGAUGAGXCGAAAUCUGAAC3329GTTCAGATTTTTTTTCT3534HS GATA6PR 1634AAGAAAAACUGAUGAG3535HSGATA6PR X 3330TTCAGATTTTTTTTCTTAAUCUGAA 1635AAAAGAAACUGAUGAGXCGAAAAAUCUGA3331TCAGATTTTTTTTCTTT3536HS GATA6PR 1636CAAAGAAACUGAUGAGXCGAAAAAAUCUG3332CAGATTTTTTTTCTTTG3537HS GATA6PR 3538 HSGATA6PR 1637 ACAAAGAA CUGAUGAG X CGAA AAAAAUCU 3333 AGATTTTT T TTCTTTGT 3539 HSGATA6PR 1638 CACAAAGA CUGAUGAG X CGAA AAAAAAUC 3334 GATTTTTT T TCTTTGIG 1639UCACAAAGCUGAUGAGXCGAAAAAAAAAU3335ATTTTTTTTCTTTGIGA3540HS GATA6PR 1640UUCACAAACUGAUGAG3541HSGATA6PR X CGAA TTTTTTTTCTTTGIGAA3336 1641CAUUCACACUGAUGAGXCGAAAGAAAAAA3337TTTTTTCTTTGTGAATG3543HS GATA6PR 1642UCAUUCACCUGAUGAGXCGAAAAGAAAAA3338TTTTTCTTTGTGAATGA3544HS GATA6PR 1643CCAGAAUACUGAUGAGXCGAAAUUUCAUU3339AATGAAATATATTCIGG3556HS GATA6PR 1644GGCCAGAACUGAUGAGXCGAAAUAUUUCA3340TGAAATATATTCTGGCC3558HS GATA6PR 1645UGGGCCAGCUGAUGAGXCGAAAUAUADUU3341AAATATATTCTGGCCCA3560HS GATA6PR 1646GUGGGCCACUGAUGAGXCGAAAAUAUAUU3342AATATATTTTGGCCCAC3561HS GATA6PR 3582 HSGATA6PR 1647 UGAAAGGA CUGAUGAG X CGAA AUCGCCCU 3343 AGGGCGAT T TCCTTTCA 3583 HSGATA6PR 1648 CUGAAAGG CUGAUGAG X CGAA AAUCGCCC 3344 GGGCGATT T CCTTTCAG 3584 HSGATA6PR 1649 ACUGAAAG CUGAUGAG X CGAA AAAUCGCC 3345 GGCGATTT C CTTTCAGT 3587 HSGATA6PR 1650 AAAACUGA CUGAUGAG X CGAA AGGAAAUC 3346 GATTTCCT T TCAGTTTT 3588 HSGATA6PR 1661 AAAAACUG CUGAUGAG X CGAA AAGGAAAU 3347 ATTTCCTT T CAGTTTTT 3589 HSGATA6PR 1652 AAAAAACU CUGAUGAG X CGAA AAAGGAAA 3348 TTTOCTTT C AGTTTTTT 3593 HSGATA6PR 1653 AAGGAAAA CUGAUGAG X CGAA ACUGAAAG 3349 CTTTCAGT T TTTTCCTT 3594 HSGATA6PR 1654 AAAGGAAA CUGAUGAG X CGAA AACUGAAA 3350 TTTCAGTT T TTTCCTTT 3595 HSGATA6PR 1655 AAAAGGAA CUGAUGAG X CGAA AAAACUGA 3352 TCAGTTTT T TCCTTTTG 3597 HSGATA6PR 1657 GCAAAAGG CUGAUGAG X CGAA AAAAACUG 3353 CAGTTTTT T CCTTTTGC 3598 HSGATA6PR 1658 UGCAAAAG CUGAUGAG X CGAA AAAAAACU 3354 AGTTTTTT C CTTTTGCA 3601 HSGATA6PR 1659 CGUUGCAA CUGAUGAG X CGAA AGGAAAAA 3355 TTTTTCCT T TTGCAACG 3602 HSGATA6PR 1660 ACGUUGCA CUGAUGAG X CGAA AAGGAAAA 3356 TTTTCCTT T TGCAACGT 3603 HSGATA6PR 1661 CACGUUGC CUGAUGAG X CGAA AAAGGAAA 3357 TTTCCTTT T GCAACGIG 3615 HSGATA6PR 1662 GAGACUUC CUGAUGAG X CGAA AGGCACGU 3358 ACGIGCCT T GAAGTCTC 3621 HSGATA6PR 1663 AGCUUUGA CUGAUGAG X CGAA ACUUCAAG 3359 CTTGAAGT C TCAAAGCT 3623 HSGATA6PR 1664 UGAGCUUU CUGAUGAG X CGAA AGACUUCA 3360 TGAAGTCT C AAAGCTCA 3630 HSGATA6PR 1665 CCUCAGGU CUGAUGAG X CGAA AGCUUUGA 3361 TCAAAGCT C ACCTGAGG 3640 HSGATA6PR 1666 CCUCAGGU CUGAUGAG X CGAA ACCUCAGG 3362 CCTGAGGT T GCAGACGT 3649 HSGATA6PR 1667 UUGGGGGU CUGAUGAG X CGAA ACGUCUGC 3363 GCAGACGT T ACCCCCAA 3650 HSGATA6PR 1668 GUUGGGGG CUGAUGAG X CGAA AACGUCUG 3364 CAGACGTT A CCCCCAAC 3666 HSGATA6PR 1669 UUUCUACC CUGAUGAG X CGAA AUCUUCUG 3365 CAGAAGAT A GGTAGAAA 3670 HSGATA6PR 1670 AUCAUUUC CUGAUGAG X CGAA ACCUAUCU 3366 AGATAGGT A GAAATGAT Table III. Hammerhead ribozymes targeting GATA transcription factors (1,2,3,4, and<BR> <BR> <BR> <BR> <BR> 6) and the complementary sequences 1671GCCACUGGCUGAUGAGXCGAAAUCAUUUC3367GAAATGATTCCAGTGGC3679HS GATA6PR 1672GGCCACUGCUGAUGAGXCGAAAAUCAUUU3368AAATGATTCGAGTGGCC3680HS GATA6PR 1673AAUACAAACUGAUGAGXCGAAAGGCCACU3369AGTGGCCTCTTTGTATT3690HS GATA6PR 1674AAAAUACACUGAUGAGXCAGGAGAGGCCA3370TGGCCTCTTTGTATTTT3692HS GATA6PR 1675GAAAAUACCUGAUGAGXCGAAAAGAGGCC3371GGOCTCTTTGTATTTTC3693HS GATA6PR 1676GAAGAAAACUGAUGAGXCGAAACAAAGAG3372CTCTTTGTATTTTCTTC3696HS GATA6PR 1677AUGAAGAACUGAUGAGXCGAAAUACAAAG3373CTTTGTATTTTCTTCAT3698HS GATA6PR 1678AAUGAAGACUGAUGAGXCGAAAAUACAAA3374TTTGTATTTTCTTCATT3699HS GATA6PR 1679CAAUGAAGCUGAUGAGXCGAAAAAUACAA3375TTGTATTTTCTTCATTG3700HS GATA6PR 1680ACAAUGAACUGAUGAGXCGAAAAAAUACA3376TGTATTTTCTTCATTGT3701HS GATA6PR 1681CAACAAUGCUGAUGAGXCGAAAGAAAAUA3377TATTTTCTTCATTGTTG3703HS GATA6PR 1682UCAACAAUCUGAUGAGXCGAAAAGAAAAU3378ATTTTCTTCATTGTTGA3704HS GATA6PR 1683UACUCAACCUGAUGAGXCGAAACAAUGAA3379TTCATTGTTGTTGAGTA3707HS GATA6PR 1684AUCUACUCCUGAUGAGXCGAAACAAUGAA3380TGTTGAGTTGAGTAGAT3710HS GATA6PR 3715 HSGATA6PR 1685 XCGAAACUCAACA3381TGTTGAGTAGATTTCAGCUGAUGAG 1686UUUCCUGACUGAUGAGXCGAAAUCUACUC3382GAGTAGATTTCAGGAAA3719HS GATA6PR 1687AUUUCCUGCUGAUGAGXCGAAAAUCUACU3383AGTAGATTTCAGGAAAT3720HS GATA6PR 1688GAUUUCCUCUGAUGAGXCGAAAAAUCUAC3384GTAGATTTCAGGAAATC3721HS GATA6PR 1689CACCUCCUCUGAUGAGXCGAAAUUUCCUG3385CAGGAAATCAGGAGGTG3729HS GATA6PR 1690UAUUGUGACUGAUGAGXCGAAACACCUCC3386GGAGGTGTTTCACAATA3739HS GATA6PR 1691GUAUUGUGCUGAUGAGXCGAAAACACCUC3387GAGGTGTTTCACAATAC3740HS GATA6PR 1692UGUAUUGUCUGAUGAGXCGAAAAACACCU3388AGGTGTTTCACAATACA3741HS GATA6PR 1693UCAUUCUGCUGAUGAGXCGAAAUUGUGAA3389GATGGCCTACAGAATGA3747HS GATA6PR 1694CACAGUUACUGAUGAGXCGAAAGGCCAUC3390GATGGCCTTTAACTGTG3762HS GATA6PR 1695UCACAGUUCUGAUGAGXCGAAAAGGCCAU3391ATGGCCTTTAACTGTGA3763HS GATA6PR 1696UUCACAGUCUGAUGAGXCGAAAAAGGCCA3392TGCCTTTTAACTGTGAA3764HS GATA6PR 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.

Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes SeqRZSeq.SubstratePosTarget I.D. No. 3393GCCGACGCCUGAUGAGXCGAAACAGUCCC4172GGGACTGTCGCGTCGGC9HUMTR 211 3394CGGGCGCCCUGAUGAGXCGAAACGCGACA4173TGTCGCGTCGGCGCCCG14HUMT R211 3395CCCCUGCUCUGAUGAGXCGAAACUCCGCG4174CGCGGAGTCAGCAGGGG32HUMT R211 3396CCAUGAUCCUGAUGAGXCGAAACCGCUUU4175AAAGCGGTAGATCATGG52HUMT R211 3397GUUGCCAUCUGAUGAGXCGAAAUCUACCG4176CGGTAGATCATGGCAAC56HUMT R211 3398AUUUCUUCCUGAUGAGXCGAAAUGGUUGC4177GCAACCATAGAAGAAAT68HUMT R211 3399UGAUGUGCCUGAUGAGXCGAAAUUUCUUC4178GAAGAAATTGCACATCA77HUMT R211 3400AAUAAUUUCUGAUGAGXCGAAAUGUGCAA4179TTGCACATCAAATTATT84HUMT R211 89 UGUUCAAUCUGAUGAGXCGAAAUUUGAUG4180CATCAAATTATTGAACA3401 3402UUGUUCAACUGAUGAGXCGAAAAUUUGAU4181ATCAAATTATTGAACAA90HUMT R211 3403UGUUGUUCCUGAUGAGXCGAAAUAAUUUG4182CAAATTATTGAACAACA92HUMT R211 3404UCUGUAACCUGAUGAGXCGAAAUCUCUCC4183GGAGAGATTGTTACAGA113HUM TR211 3405UGCUCUGUCUGAUGAGXCGAAACAAUCUC4184GAGATTGTTACAGAGCA116HUM TR211 3406CUGCUCUGCUGAUGAGXCGAAAACAAUCU4185AGATTGTTACAGAGCAG117HUM TR211 143 HUMTR211 3407 ACAAUCUS CUGAUGAG X CGAA AUUUUCUG 4186 CAGAAAAT C CAGATTGT 149 HUMTR211 3408 GCUGUCAC CUGAUGAG X CGAA AUCUGGAU 4187 ATCCAGAT T GTGACAGC 161 HUMTR211 3409 UUAUGAUC CUGAUGAG X CGAA AGUGCUGU 4188 ACAGCACT T GATCATAA 165 HUMTR211 3410 GGUAUUAU CUGAUGAG X CGAA AUCAAGUG 4189 CACTTGAT C ATAATACC 168 HUMTR211 3411 UUGGGUAU CUGAUGAG X CGAA AUGAUCAA 4190 TTGATCAT A ATACCCAA 3412GCCUUGGGCUGAUGAGXCGAAAUUAUGAU4191ATCATAATACCCAAGGC171HUM TR211 187 HUMTR211 3413 UCAGAAUG CUGAUGAG X CGAA ACUGCUUG 4192 CAAGCAGT T CATTCTGA 3414GUCAGAAUCUGAUGAGXCGAAAACUGCUU4193AAGCAGTTCATTCTGAC188HUM TR211 191 HUMTR211 3415 UUUGUCAG CUGAUGAG X CGAA AUGAACUS 4194 CAGTTCAT T CTGACAAA 192 HUMTR211 3416 AUUUGUCA CUGAUGAG X CGAA AAUGAACU 4195 AGTTCATT C TGACAAAT 201 HUMTR211 3417 GCCGUCGU CUGAUGAG X CGAA AUUUGUCA 4196 TGACAAAT C ACGACGGC 3418UUGGAGUACUGAUGAGXCGAAAGCCGUCG4197CGACGGCTCTACTCCAA211HUM TR211 213 HUMTR211 3419 GCUUGGAG CUGAUGAG X CGAA AGAGCCGU 4198 ACGGCTCT A CTCCAAGC 216 HUMTR211 3420 UUUGCUUG CUGAUGAG X CGAA AGUAGAGC 4199 GCTCTACT C CAAGCAAA 227227HUMTR211 3421 GCCAGAAU CUGAUGAG X CGAA ACUUUGCU 4200 AGCAAAGT C ATTCTGGC 230 HUMTR211 3422 CUGGCCAG CUGAUGAG X CGAA AUGACUUU 4201 AAAGTCAT T CTGGCCAG 231 HUMTR211 3423 CCUGGCCA CUGAUGAG X CGAA AAUGACUU 4202 AAGTCATT C TGGCCAGG 246 HUMTR211 3424 CGGAGUGG CUGAUGAG X CGAA AUCUUGCC 4203 GGCAAGAT T CCACTCCG 247 HUMTR211 3425 CCGGAGUG CUGAUGAG X CGAA AAUCUUGC 4204 GCAAGATT C CACTCCGG 252 HUMTR211 3426 UUUUCCCG CUGAUGAG X CGAA AGUGGAAU 4205 ATTCCACT C CGGGAAAA 263 HUMTR211 3427 GUAAGGAA CUGAUGAG X CGAA ACUUUUCC 4206 GGAAAAGT T TICCTTAC 264 HUMTR211 3428 UGUAAGGA CUGAUGAG X CGAA AACUUUUC 4207 GAAAAGTT T TCCTTACA 265 HUMTR211 3429 UUGUAAGG CUGAUGAG X CGAA AAACUUUU 4208 AAAAGTTT T CCTTACAA 266 HUMTR211 3430 GUUGUAAG CUGAUGAG X CGAA AAAACUUU 4209 AAAGTTTT C CTTACAAC 269 HUMTR211 3431 GGAGUUGU CUGAUGAG X CGAA AGGAAAAC 4210 GTTTTCCT T ACAACTCC 270 HUMTR211 3432 UGGAGUUG CUGAUGAG X CGAA AAGGAAAA 4211 TTTTCCTT A CAACTCCA 276 HUMTR211 3433 UGCAUCUG CUGAUGAG X CGAA AGUUGUAA 4212 TTACAACT C CAGATGCA 293 HUMTR211 3434 AACUGGUU CUGAUGAG X CGAA ACACCUGC 4213 GCAGGIGT C AACCAGTT 301 HUMTR211 3435 UAAAAAAU CUGAUGAG X CGAA ACUGGUUG 4214 CAACCAGT T ATTTTTTA Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 302 HUMTR211 3436 GUAAAAAA CUGAUGAG X CGAA AACUGGUU 4215 AACCAGTT A TTTTTTAC 3437UGGUAAAACUGAUGAGXCGAAAUAACUGG4216CCAGTTATTTTTTACCA304HUM TR211 3438GUGGUAAACUGAUGAGXCGAAAAUAACUG4217CAGTTATTTTTTACCAC305HUM TR211 306 AGUGGUAACUGAUGAGXCGAAAAAUAACU4218AGTTATTTTTTACCACT3439 3440G@GUGGUACUGAUGAGXCGAAAAAAUAAC4219GTTATTTTTTACCACTC307HUM TR211 3441GGAGUGGUCUGAUGAGXCGAAAAAAAUAA4220TTATTTTTTACCACTCC308HUM TR211 3442AGGAGUGGCUGAUGAGXCGAAAAAAAAUA4221TATTTTTTACCACTCCT309HUM TR211 3443CAGAUCAGCUGAUGAGXCGAAAGUGGUAA4222TTACCACTCCTGATCTG315HUM TR211 3444UGCAGACACUGAUGAGXCGAAAUCAGGAG4223CTCCTGATCTGTCIGCA321HUM TR211 3445GUUGUGCACUGAUGAGXCGAAACAGAUCA4224TGATCTGTCTGCACAAC325HUM TR211 3446UCUGUUAGCUGAUGAGXCGAAAGCUGCAG4225CTGCAGCTCCTAACAGA344HUM TR211 3447UUAUCUGUCUGAUGAGXCGAAAGGAGCUG4226CAGCTCCTAACAGATAA347HUM TR211 3448UGGAGAAUCUGAUGAGXCGAAAUCUGUUA4227TAACAGATAATTCTCCA354HUM TR211 3449GUCUGGAGCUGAUGAGXCGAAAUUAUCUG4228CAGATAATTCTCCAGAC357HUM TR211 3450GGUCUGGACUGAUGAGXCGAAAAUUAUCU4229AGATAATTCTCCAGACC358HUM TR211 3451UUGGUCUGCUGAUGAGXCGAAAGAAUUAU4230ATAATTCTCCAGACCAA360HUM TR211 3452AAAAACCUCUGAUGAG378HUMTR211 X 4231GACCAAATAAGGTTTTTAUUUGGUC 3453AGAUCAAACUGAUGAGXCGAAACCUUAUU4232AATAAGGTTTTIGATCT383HUM TR211 3452AAGAUCAACUGAUGAGXCGAAAACCUUAU4233ATAAGGTTTTTGATCTT384HUM TR211 3455AAAGAUCACUGAUGAGXCGAAAAACCUUA4234TAAGGTTTTTGATCTTT385HUM TR211 3456CAAAGAUCCUGAUGAGXCGAAAAAACCUU4235AAGGTTTTTGATCTTTG386HUM TR211 3457UACGCAAACUGAUGAGXCGAAAUCAAAAA4236TTTTTGATCTTTGCGTA390HUM TR211 3458ACUACGCACUGAUGAGXCGAAAGAUCAAA4237TTTGATCTTTGCGTAGT392HUM TR211 3459UACUACGCCUGAUGAGXCGAAAAGAUCAA4238TTGATCTTTGCGTAGTA393HUM TR211 3460CCACAUACCUGAUGAGXCGAAACGCAAAG4239CTTTGCGTAGTATGTGG398HUM TR211 401 HUMTR211 3461 UCUCCACA CUGAUGAG X CGAA ACUACGCA 4240 TGCGTAGT A TGTGGAGA 418 HUMTR211 3462 XCGAAAUGCUUUG4241CAAAGCATCAGGACGTCCUGAUGAG 3463UCCAUAAUCUGAUGAGXCGAAACGUCCUG4242CAGGACGTCATTATGGA426HUM TR211 3464UGCUCCAUCUGAUGAGXCGAAAUGACGUC4243GACGTCATTATGGAGCA429HUM TR211 3465CUGCUCCACUGAUGAGXCGAAAAUGACGU4244ACGTCATTATGGAGCAG430HUM TR211 3466UCACAAGUCUGAUGAGXCGAAACUGCUCC4245GGAGCAGTAACTIGTGA440HUM TR211 3467GCCUUCACCUGAUGAGXCGAAAGUUACUG4246CAGTAACTTGTGAAGGC444HUM TR211 463 UUUUAAAACUGAUGAGXCGAAAUCCUUUG4247CAAAGGATTTTTTAAAA3468 3469CUUUUAAACUGAUGAGXCGAAAAUCCUUU4248AAAGGATTTTTTAAAAG464HUM TR211 3470UCUUUUAACUGAUGAGXCGAAAAAUCCUU4249AAGGATTTTTTAAAAGA465HUM TR211 3471UUCUUUUACUGAUGAGXCGAAAAAAUCCU4250AGGATTTTTTAAAAGAA466HUM TR211 3472CUUCUUUUCUGAUGAGXCGAAAAAAAUCC4251GGATTTTTTAAAAGAAG467HUM TR211 3473GCUUCUUUCUGAUGAGXCGAAAAAAAAUC4252GATTTTTTAAAAGAAGC468HUM TR211 3474UUUUUUCGCUGAUGAGXCGAAAUGCUUCU4253AGAAGCATCCGAAAAAA479HUM TR211 3475AUAUACUACUGAUGAGXCGAAAUUUUUUU4254GAAAAAATTTAGTATAT489HUM TR211 3476AAUAUACUCUGAUGAGXCGAAAAUUUUUU4255AAAAAATTTAGTATATT490HUM TR211 3477GAAUAUACCUGAUGAGXCGAAAAAUUUUU4256AAAAATTTAGTATATIC491HUM TR211 3478CAUGAAUACUGAUGAGXCGAAACUAAAUU4257AATTTAGTATATTCATG494HUM TR211 3479GACAUGAACUGAUGAGXCGAAAUACUAAA4258TTTAGTATATTCATGIC496HUM TR211 3480UCGACAUGCUGAUGAGXCGAAAUAUACUA4259TAGTATATTCATGTCGA498HUM TR211 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3481CUCGACAUCUGAUGAGXCGAAAAUAUACU4260AGTATATTCATGTCGAG499HUM TR211 3482UGAUCCUCCUGAUGAGXCGAAACAUGAAU4261ATTCATGTCGAGGATCA504HUM TR211 511 AAUCCUUUCUGAUGAGXCGAAAUCCUCGA4262TCGAGGATCAAAGGATT3483 3484AAUAAUACCUGAUGAGXCGAAAUCCUUUG4263CAAAGGATTGTATTATT519HUM TR211 3485AUUAAUAACUGAUGAGXCGAAACAAUCCU4264AGGATTGTATTATTAAT522HUM TR211 3486UUAUUAAUCUGAUGAGXCGAAAUACAAUC4265GATTGTATTATTAATAA524HUM TR211 525 CUUAUUAACUGAUGAGXCGAAAAUACAAU4266ATTGTATTATTAATAAG3487 527 UGCUUAUUCUGAUGAGXCGAAAUAAUACA4267TGTATTATTAATAAGCA3488 3489GUGCUUAUCUGAUGAGXCGAAAAUAAUAC4268GTATTATTAATAAGCAC528HUM TR211 3490GUGGUGCUCUGAUGAGXCGAAAUUAAUAA4269TTATTAATAAGCACCAC531HUM TR211 3491GCAGUAUUCUGAUGAGXCGAAACAGCGGU4270ACCGCTGTCAATACTGC552HUM TR211 3492ACCUGCAGCUGAUGAGXCGAAAUUGACAG4271CTGTCAATACTGCAGGT556HUM TR211 3493AUCUCUGUCUGAUGAGXCGAAACCUGCAG4272CTGCAGGTTACAGAGAT565HUM TR211 566 HUMTR211 3494 CAUCUCUG CUGAUGAG X CGAA AACCUGCA 4273 TGCAGGTT A CAGAGATG 576 HUMTR211 3495 AAACGCAA CUGAUGAG X CGAA ACAUCUCU 4274 AGAGATGT A TTGCGTTT 578 HUMTR211 3496 CCAAACGC CUGAUGAG X CGAA AUACAUCU 4275 AGATGTAT T GCGTTTGG 3497UCAUUCCACUGAUGAGXCGAAACGCAAUA4276TATTGCGTTTGGAATGA583HUM TR211 584 UUCAUUCCCUGAUGAGXCGAAAACGCAAU4277ATTGCGTTTGGAATGAA3498 3499AUUGGACACUGAUGAGXCGAAAGUCUUGC4278GCAAGACTCTGTCCAAT601HUM TR211 3500UCACAUUGCUGAUGAGXCGAAACAGAGUC4279GACTCTGTCCAATGTGA605HUM TR211 626 HUMTR211 3501 GAUACUUC CUGAUGAG X CGAA AUGGGUUU 4280 AAACCCAT T GAAGTATC 632 HUMTR211 3502 UCUCGUGA CUGAUGAG X CGAA ACUUCAAU 4281 ATTGAAGT A TCACGAGA 634 HUMTR211 3503 UUUCUCGU CUGAUGAG X CGAA AUACUUCA 4582 TGAAGTAT C ACGAGAAA 646 HUMTR211 3504 AGUUGGAA CUGAUGAG X CGAA AUUUUUUU 4283 AGAAAAAT C TTCCAACT 648 HUMTR211 3505 ACAGUUGG CUGAUGAG X CGAA AGAUUUUU 4284 AAAAATCT T CCAACTGT 649 HUMTR211 3506 CACAGUUG CUGAUGAG X CGAA AAGAUUUU 4285 AAAATCTT C CAACTGIG 663 HUMTR211 3507 UUCUGUUG CUGAUGAG X CGAA AGCGGCAC 4286 GTGCCGCT T CAACAGAA 664 HUMTR211 3508 UUUCUGUU CUGAUGAG X CGAA AAGCGGCA 4287 TGCCGCTT C AACAGAAA 677 HUMTR211 3509 CGGAUAUA CUGAUGAG X CGAA AUUUUUUU 4288 GAAAAAAT C TATATCCG 679 HUMTR211 3510 UUCGGAUA CUGAUGAG X CGAA AGAUUUUU 4289 AAAAATCT A TATCCGAA 681 HUMTR211 3511 CUUUCGGA CUGAUGAG X CGAA AUAGAUUU 4290 AAATCTAT A TCCGAAAG 683 HUMTR211 3512 UCCUUUCG CUGAUGAG X CGAA AUAUAGAU 4291 ATCTATAT C CGAAAGGA 695 HUMTR211 3513 GGGCUACG CUGAUGAG X CGAA AGGUCCUU 4292 AAGGACCT T CGTAGCCC 696 HUMTR211 3514 UGGGCUAC CUGAUGAG X CGAA AAGGUCCU 4293 AGGACCTT C GTAGCCCA 699 HUMTR211 3515 UAAUGGGC CUGAUGAG X CGAA ACGAAGGU 4294 ACCTTCGT A GCCCATTA 706 HUMTR211 3516 UUGCAGUU CUGAUGAG X CGAA AUGGGCUA 4295 TAGCCCAT T AACIGCAA 707 HUMTR211 3517 GUUGCAGU CUGAUGAG X CGAA AAUGGGCU 4296 AGCCCATT A ACTGCAAC 717 HUMTR211 3518 AAAAGUUG CUGAUGAG X CGAA AGUUGCAG 4297 CTGCAACT C CAACTTTT 723 HUMTR211 3519 UGUUACAA CUGAUGAG X CGAA AGUUGGAG 4298 CTCCAACT T TTGTAACA 724 HUMTR211 3520 CUGUUACA CUGAUGAG X CGAA AAGUUGGA 4299 TCCAACTT T TGTAACAG 725 HUMTR211 3521 UCUGUUAC CUGAUGAG X CGAA AAAGUUGG 4300 CCAACTTT T GTAACAGA 728 HUMTR211 3522 CUAUCUGU CUGAUGAG X CGAA ACAAAAGU 4301 ACTTTTGT A ACAGATAG 735 HUMTR211 3523 ACUUUCAC CUGAUGAG X CGAA AUCUGUUA 4302 TAACAGAT A GIGAAAGT 744 HUMTR211 3524 UGACCUUG CUGAUGAG X CGAA ACUUUCAC 4303 GTGAAAGT A CAAGGTCA 751 HUMTR211 3525 GUCCUGUU CUGAUGAG X CGAA ACCUUGUA 4304 TACAAGGT C AACAGGAC Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3526CUGAAUCUCUGAUGAGXCGAAACAGUCCU4305AGGACTGTTAGATTCAG763HUM TR211 3527CCUGAAUCCUGAUGAGXCGAAAACAGUCC4306GGACTGTTAGATTCAGG764HUM TR211 768 CAUUCCUGCUGAUGAGXCGAAAUCUAACA4307TGTTAGATTCGGGAATG3528 3529ACAUUCCUCUGAUGAGXCGAAAAUCUAAC4308GTTAGATTCAGGAATGT769HUM TR211 3530UAUUCAUCCUGAUGAGXCGAAACAUUCCU4309AGGAATGTTCATGAATA778HUM TR211 3531AUAUUCAUCUGAUGAGXCGAAAACAUUCC4310GGAATGTTCATGAATAT779HUM TR211 3532UGGAUGAACUGAUGAGXCGAAAUUCAUGA4311TCATGAATATICATCCA786HUM TR211 3533GAUGGAUGCUGAUGAGXCGAAAUAUUCAU4312ATGAATATTCATCCATC788HUM TR211 789 HUMTR211 3534 AGAUGGAU CUGAUGAG X CGAA AAUAUUCA 4313 TGAATATT C A@CCATCT 3535UCCAGAUGCUGAUGAGXCGAAAUGAAUAU4314ATATTCATCCATCTGGA792HUM TR211 3536UUACUCCACUGAUGAGXCGAAAUGGAUGA4315TCATCCATC@GGAGTAA796HUM TR211 3537UCAGUUUUCUGAUGAGXCGAAACUCCAGA4316TCTGGAGTAAAAACTGA803HUM TR211 3538GCACAGCUCUGAUGAGXCGAAACUCAGUU4317AACTGAGTCAGCTGTGC814HUM TR211 3539CCUUAUCUCUGAUGAGXCGAAAUGUCAUC4318GATGACATCAGATAAGG832HUM TR211 837 UUCAGCCUCUGAUGAGXCGAAAUCUGAUG4319CATCAGATAAGGCTGAA3540 3541CCUGACAUCUGAUGAGXCGAAAUUCAGCC4320GGCTGAATCATGTCAGG847HUM TR211 3542AUCUCCCUCUGAUGAGXCGAAACAUGAUU4321AATCATGTCAGGGAGAT852HUM TR211 3543UGUACUUACUGAUGAGXCGAAAUCUCCCU4322AGGGAGATCTAAGTACA861HUM TR211 3544AUGUACUUCUGAUGAGXCGAAAAUCUCCC4323GGGAGATTTAAGTACAT862HUM TR211 863 AAUGUACUCUGAUGAGXCGAAAAAUCUCC4324GGAGATTTAAGTACATT3545 3546GGCCAAUGCUGAUGAGXCGAAACUUAAAU4325ATTTAAGTACATTGGCC867HUM TR211 3547CAUUGGCCCUGAUGAGXCGAAAUGUACUU4326AAGTACATTGGCCAATG871HUM TR211 3548AAUGAUGUCUGAUGAGXCGAAACCACAUU4327AATGTGGTTACATCATT884HUM TR211 885 UAAUGAUGCUGAUGAGXCGAAAACCACAU4328ATGTGGTTACATCATTA3549 3550UCGCUAAUCUGAUGAGXCGAAAUGUAACC4329GGTTACATCATTAGCGA889HUM TR211 3551GAUUCGCUCUGAUGAGXCGAAAUGAUGUA4330TACATCATTAGCGAATC892HUM TR211 893 AGAUUCGCCUGAUGAGXCGAAAAUGAUGU4331ACATCATTAGCGAATCT3552 3553UUUUCCAACUGAUGAGXCGAAAUUCGCUA4332TAGCGAATCITGGAAAA900HUM TR211 3554GUUUUUCCCUGAUGAGXCGAAAGAUUCGC4333GCGAATCTTGGAAAAAC902HUM TR211 3555AAGAUCUUCUGAUGAGXCGAAAGUUUUUC4334GAAAAACTAAAGATCTT912HUM TR211 918 UUGAGAAACUGAUGAGXCGAAAUCUUUAG4335CTAAAGATCTTTCTCAA3556 920 UUUUGAGACUGAUGAGXCGAAAGAUCUUU4336AAAGATCTTTCTCAAAA3557 3558AUUUUGARCUGAUGAGXCGAAAAGAUCUU4337AAGATCTTTCTCAAAAT921HUM TR211 3559UAUUUUGACUGAUGAGXCGAAAAAGAUCU4338AGATCTTTCTCAAAATA922HUM TR211 924 ACUAUUUUCUGAUGAGXCGAAAGAAAGAU4339ATCTTTCTCAAAATAGT3560 3561UUCAUUACCUGAUGAGXCGAAAUUUUGAG4340CTCAAAATAGTAATGAA930HUM TR211 3562CAUUUCAUCUGAUGAGXCGAAACUAUUUU4341AAAATAGTAATGAAATG933HUM TR211 943 HUMTR211 3563 CAAUCAUA CUGAUGAG X CGAA ACAUUUCA 4342 TGAAATGT C TATGATTG 3564UUCAAUCACUGAUGAGXCGAAAGACAUUU4343AAATGTCTATGATTGAA945HUM TR211 950 HUMTR211 3565 AAGCUUUCCUGAUGAG X 4344TCTATGATTGAAAGCTTAUCAUAGA 3566CAUUGCUUCUGAUGAGXCGAAAGCUUUCA4345TGAAAGCTTAAGCAATG958HUM TR211 3567UCAUUGCUCUGAUGAGXCGAAAAGCUUUC4346GAAAGCTTAAGCAATGA959HUM TR211 3568CAAAGAGGCUGAUGAGXCGAAAUCAUCAU4347ATGATGATACCTCTTTG972HUM TR211 3569CACACAAACUGAUGAGXCGAAAGGUAUCA4348TGATACCTCTTTGTGTG976HUM TR211 3570UUCACACACUGAUGAGXCGAAAGAGGUAU4349ATACCTCTTTGTGTGAA978HUM TR211 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 979 AUUCACACCUGAUGAGXCGAAAAGAGGUA4350TACCTCTTTGTGTGAAT3571 988 UUUCUUGACUGAUGAGXCGAAAUUCACAC4351GTGTGAATTTCAAGAAA3572 3573AUUUCUUGCUGAUGAGXCGAAAAUUCACA4352TGTGAATTTCAAGAAAT989HUM TR211 3574CAUUUCUUCUGAUGAGXCGAAAAAUUCAC4353GTGAATTTCAAGAAATG990HUM TR211 1016 GCCCUUGACUGAUGAGXCGAAACAUCACC4354GGTGATGTTTCAAGGGC3575 1017 UGCCCUUGCUGAUGAGXCGAAAACAUCAC4355GTGATGTTTCAAGGGCA3576 3577AUGCCCUUCUGAUGAGXCGAAAAACAUCA4356TGATGTTTCAAGGGCAT1018HU MTR211 1027 HUMTR211 3578 XCGAAAUGCCCUU4357AAGGGCATTTGACACTCCUGAUGAG 3579AGAGUGUCCUGAUGAGXCGAAAAUGCCCU4358AGGGCATTTGACACTCT1028HU MTR211 3580UUUUGCAACUGAUGAGXCGAAAGUGUCAA4359TTGACACTCTTGCAAAA1035HU MTR211 3581GCUUUUGCCUGAUGAGXCGAAAGAGUGUC4360GACACTCTTGCAAAAGC1037HU MTR211 1048 C@GGAUUCCUGAUGAGXCGAAAUGCUUUU4361AAAAGCATTGAATCCTG3582 3583CUCUCCAGCUGAUGAGXCGAAAUUCAAUG4362CATTGAATCCTGGAGAG1053HU MTR211 3584CCGCUACUCUGAUGAGXCGAAAGCUCUGG4363CCAGAGCTCAGTAGCGG1081HU MTR211 3585AUGCCCGCCUGAUGAGXCGAAACUGAGCU4364AGCTCAGTAGCGGGCAT1085HU MTR211 1106 HUMTR211 3586 AUUAGGUG CUGAUGAG X CGAA ACACUUCC 4365 GGAAGTGT A CACCTAAT 3587CCAGUGAUCUGAUGAGXCGAAAGGUGUAC4366GTACACCTAATCACTGG1112HU MTR211 3588UCUCCAGUCUGAUGAGXCGAAAUUAGGUG4367CACCTAATCACTGGAGA1115HU MTR211 3589UAUGCUUGCUGAUGAGXCGAAAUCUCCAG4368CTGGAGATTCAAGCATA1125HU MTR211 3590UUAUGCUUCUGAUGAGXCGAAAAUCUCCA4369TGGAGATTCAAGCATAA1126HU MTR211 1133 GUGUAAUUCUGAUGAGXCGAAAUGCUUGA4370TCAAGCATAAATTACAC3591 3592UUCGGUGUCUGAUGAGXCGAAAUUUAUGC4371GCATAAATTACACCGAA1137HU MTR211 3593UUUCGGUGCUGAUGAGXCGAAAAUUUAUG4372CATAAATTACACCGAAA1138HU MTR211 3594UCGCUGAGCUGAUGAGXCGAAAGUGGCCC4373GGGCCACTTCTCAGCGA1160HU MTR211 3595AUCGCUGACUGAUGAGXCGAAAAGUGGCC4374GGCCACTTCTCAGCGAT1161HU MTR211 3596GAAUCGCUCUGAUGAGXCGAAAGAAGUGG4375CCACTTCTCAGCGATTC1163HU MTR211 3597UACAUGUGCUGAUGAGXCGAAAUCGCUGA4376TCAGCGATTCACATGTA1170HU MTR211 3598CUACAUGUCUGAUGAGXCGAAAAUCGCUG4377CAGCGATTCACATGTAG1171HU MTR211 3599CUGAAAGCCUGAUGAGXCGAAACAUGUGA4378TCACATGTAGCTTTCAG1178HU MTR211 3600GAGCCUGACUGAUGAGXCGAAAGCUACAU4379ATGTAGCTTTCAGGCTC1182HU MTR211 3601UGAGCCUGCUGAUGAGXCGAAAAGCUACA4380TGTAGCTTTCAGGCTCA1183HU MTR211 3602GUGAGCCUCUGAUGAGXCGAAAAAGCUAC4381GTAGCTTTCAGGCTCAC1184HU MTR211 3603GGCAUGGUCUGAUGAGXCGAAAGCCUGAA4382TTCAGGCTCACCATGCC1190HU MTR211 3604CAUAGGAGCUGAUGAGXCGAAAGGCAUGG4383CCATGCCTTCTCCTATG1200HU MTR211 3605GCAUAGGACUGAUGAGXCGAAAAGGCAUG4384CATGCCTTCTCCTATGC1201HU MTR211 3606AGGCAUAGCUGAUGAGXCGAAAGAAGGCA4385TGCCTTCTCCTATGCCT1203HU MTR211 3607CUCAGGCACUGAUGAGXCGAAAGGAGAAG4386CTTCTCCTATGCCTGAG1206HU MTR211 3608CAUUCAGGCUGAUGAGXCGAAACUCAGGC4387GCCTGAGTACCTGAATG1216HU MTR211 3609CCCCAAUGCUGAUGAGXCGAAAGUGCACA4388TGTGCACTACATTGGGG1231HU MTR211 3610GACUCCCCCUGAUGAGXCGAAAUGUAGUG4389CACTACATTGGGGAGTC1235HU MTR211 3611UGGAGGCACUGAUGAGXCGAAACUCCCCA4390TGGGGAGTCTGCCTCCA1243HU MTR211 3612GCAGUCUGCUGAUGAGXCGAAAGGCAGAC4391GTCTGCCTCCAGACTGC1249HU MTR211 3613UUGAUAAGCUGAUGAGXCGAAACAGCAGU4392ACTGCTGTTCTTATCAA1261HU MTR211 3614AUUGAUAACUGAUGAGXCGAAAACAGCAG4393CTGCTGTTCTTATCAAT1262HU MTR211 3615GCAUUGAUCUGAUGAGXCGAAAGAACAGC4394GCTGTTCTTATCAATGC1264HU MTR211 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3616UGCAUUGACUGAUGAGXCGAAAAGAACAG4395CTGTTCTTATCAATGCA1265HU MTR211 3617AGUGCAUUCUGAUGAGXCGAAAUAAGAAC4396GTTCTTATCAATGCACT1267HU MTR211 3618GGAAUCGACUGAUGAGXCGAAAGUGCCCA4397TGGGCACTTTCGATTCC1283HU MTR211 3619AGGAAUCGCUGAUGAGXCGAAAAGUGCCC4398GGGCACTTTCGATTCCT1284HU MTR211 3620AAGGAAUCCUGAUGAGXCGAAAAAGUGCC4399GGCACTTTCGATTCCTT1285HU MTR211 3621AAAGAAGGCUGAUGAGXCGAAAUCGAAAG4400CTTTCGATTCCTTCTTT1289HU MTR211 3622GAAAGAAGCUGAUGAGXCGAAAAUCGAAA4401TTTCGATTCCTTCTTTC1290HU MTR211 3623CUGGAAAGCUGAUGAGXCGAAAGGAAUCG4402CGATTCCTTCTTTCCAG1293HU MTR211 3624CCUGGAAACUGAUGAGXCGAAAAGGAAUC4403GATTCCTTCTTTCCAGG1294HU MTR211 3625AGCCUGGACUGAUGAGXCGAAAGAAGGAA4404TTCCTTCTTTCCAGGCT1296HU MTR211 3626GAGCCUGGCUGAUGAGXCGAAAAGAAGGA4405TCCTTCTTTCCAGGCTC1297HU MTR211 3627AGAGCCUGCUGAUGAGXCGAAAAAGAAGG4406CCTTCTTTCCAGGCTCT1298HU MTR211 3628UUGCCCUACUGAUGAGXCGAAAGCCUGGA4407TCCAGGCTCTAGGGCAA1305HU MTR211 3629UCUUGCCCCUGAUGAGXCGAAAGAGCCUG4408CAGGCTCTAGGGCAAGA1307HU MTR211 3630ACCAGUGACUGAUGAGXCGAAAUGCUGUU4409AACAGCATATCACTGGT1325HU MTR211 3631UCACCAGUCUGAUGAGXCGAAAUAUGCUG4410CAGCATATCACTGGTGA1327HU MTR211 3632AUUCCAGUCUGAUGAGXCGAAAGCUUUCA4411TGAAAGCTTACTGGAAT1341HU MTR211 1342 HUMTR211 3633 CAUUCCAG CUGAUGAG X CGAA AAGCUUUC 4412 GAAAGCTT A CTGGAATG 1355 HUMTR211 3634 AGAGUAAA CUGAUGAG X CGAA AGUUCAUU 4413 AATGAACT T TTTACTCT 1356 HUMTR211 3635 AAGAGUAA CUGAUGAG X CGAA AAGUUCAU 4414 ATGAACTT T TTACTCTT 3636CAAGAGUACUGAUGAGXCGAAAAAGUUCA4415TGAACTTTTTACTCTTG1357HU MTR211 3637CCAAGAGUCUGAUGAGXCGAAAAAAGUUC4416GAACTTTTTACTCTTGG1358HU MTR211 1359 HUMTR211 3638 ACCAAGAG CUGAUGAG X CGAA AAAAAGUU 4417 AACTTTTT A CTCTTGGT 1362 HUMTR211 3639 AAGACCAA CUGAUGAG X CGAA AGUAAAAA 4418 TTTTTACT C TTGGTCTT 1364 HUMTR211 3640 GCAAGACC CUGAUGAG X CGAA AGAGUAAA 4419 TTTACTCT T GGTCTTGC 1368 HUMTR211 3641 CUGGGCAA CUGAUGAG X CGAA ACCAAGAG 4420 CTCTIGGT C TTGCCCAG 1370 HUMTR211 3642 CACUGGGC CUGAUGAG X CGAA AGACCAAG 4421 CTTGGTCT T GCCCAGIG 1397 HUMTR211 3643 AUAGUUGC CUGAUGAG X CGAA ACAUUCAU 4422 ATGAATGT A GCAACTAT 1404 HUMTR211 3644 UGCUAAUA CUGAUGAG X CGAA AGUUGCUA 4423 TAGCAACT A TATTAGCA 1406 HUMTR211 3645 GUUGCUAA CUGAUGAG X CGAA AUAGUUGC 4424 GCAACTAT A TTAGCAAC 1408 HUMTR211 3646 AUGUUGCU CUGAUGAG X CGAA AUAUAGUU 4425 AACTATAT T AGCAACAT 1409 HUMTR211 3647 AAUGUUGC CUGAUGAG X CGAA AAUAUAGU 4426 ACTATATT A GCAACATT 1417 HUMTR211 3648 AAUUGACA CUGAUGAG X CGAA AUGUUGCU 4427 AGCAACAT T TGTCAATT 1418 HUMTR211 3649 CAAUUGAC CUGAUGAG X CGAA AAUGUUGC 4428 GCAACATT T GTCAATTG 1421 HUMTR211 3650 AGACAAUU CUGAUGAG X CGAA ACAAAUGU 4429 ACATTTGT C AATTGTCT 1425 HUMTR211 3651 GUGAAGAC CUGAUGAG X CGAA AUUGACAA 4430 TTGTCAAT T GTCTTCAC 1428 HUMTR211 3652 AUUGUGAA CUGAUGAG X CGAA ACAAUUGA 4431 TCAATTGT C TTCACAAT 1430 HUMTR211 3653 CUAUUGUG CUGAUGAG X CGAA AGACAAUU 4432 AATTGTCT T CACAATAG 1431 HUMTR211 3654 ACUAUUGU CUGAUGAG X CGAA AAGACAAU 4433 ATTGTCTT C ACAATAGT 1437 HUMTR211 3655 UUGAAGAC CUGAUGAG X CGAA AUUGUGAA 4434 TTCACAAT A GTCTTCAA 1440 HUMTR211 3656 UUGUUGAA CUGAUGAG X CGAA ACUAUUGU 4435 ACAATAGT C TTCAACAA 1442 HUMTR211 3657 UCUUGUUG CUGAUGAG X CGAA AGACUAUU 4436 AATAGTCT T CAACAAGA 1443 HUMTR211 3658 AUCUUGUU CUGAUGAG X CGAA AAGACUAU 4437 ATAGTCTT C AACAAGAT 1452 HUMTR211 3659 UGACAUUU CUGAUGAG X CGAA AUCUUGUU 4438 AACAAGAT A AAATGTCA 1459 HUMTR211 3660 UUUCUGUU CUGAUGAG X CGAA ACAUUUUA 4439 TAAAATGT C AACAGAAA Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3661CCAUCAAUCUGAUGAGXCGAAAUUUUCUU4440AAGAAAATTATTGATGG1477HU MTR211 3662UCCAUCAACUGAUGAGXCGAAAAUUUUCU4441AGAAAATTATTGATGGA1478HU MTR211 1480 GCUCCAUCCUGAUGAGXCGAAAUAAUUUU4442AAAATTATTGATGGAGC3663 3664AGUUUGAACUGAUGAGXCGAAAUGUGCUC4443GAGCACATCTTCAAACT1493HU MTR211 3665GUAGUUUGCUGAUGAGXCGAAAGAUGUGC4444GCACATCTTCAAACTAC1495HU MTR211 3666UGUAGUUUCUGAUGAGXCGAAAAGAUGUG4445CACATCTTCAAACTACA1496HU MTR211 3667AACUCCUGCUGAUGAGXCGAAAGUUUGAA4446TTCAAACTACAGGAGTT1502HU MTR211 3668UGUUACAACUGAUGAGXCGAAACUCCUGU4447ACAGGAGTTTTGTAACA1510HU MTR211 3669CUGUUACACUGAUGAGXCGAAAACUCCUG4448CAGGAGTTTTGTAACAG1511HU MTR211 3670GCUGUUACCUGAUGAGXCGAAAAACUCCU4449AGGAGTTTTGTAACAGC1512HU MTR211 3671CAUGCUGUCUGAUGAGXCGAAACAAAACU4450AGTTTTGTAACAGCATG1515HU MTR211 3672CAGAGUUUCUGAUGAGXCGAAACCAUGCU4451AGCATGGTTAAACTCTG1526HU MTR211 3673GCAGAGUUCUGAUGAGXCGAAAACCAUGC4452GCATGGTTAAACTCTGC1527HU MTR211 1532 UCAAUGCACUGAUGAGXCGAAAGUUUAAC4453GTTAAACTCTGCATTGA3674 3675UAUCCAUCCUGAUGAGXCGAAAUGCAGAG4454CTCTGCATTGATGGATA1538HU MTR211 1546 CAUAUUCGCUGAUGAGXCGAAAUCCAUCA4455TGATGGATACGAATATG3676 3677GGUAGGCACUGAUGAGXCGAAAUUCGUAU4456ATACGAATATGCCTACC1552HU MTR211 3678CCUUCAGGCUGAUGAGXCGAAAGGCAUAU4457ATATGCCTACCTGAAGG1558HU MTR211 3679AAGAGUACCUGAUGAGXCGAAAUUGCCUU4458AAGGCAATAGTACTCTT1571HU MTR211 3680CUGAAGAGCUGAUGAGXCGAAACUAUUGC4459GCAATAGTACTCTTCAG1574HU MTR211 3681GGACUGAACUGAUGAGXCGAAAGUACUAU4460ATAGTACTCTTCAGTCC1577HU MTR211 3682CUGGACUGCUGAUGAGXCGAAAGAGUACU4461AGTACTCTTCAGTCCAG1579HU MTR211 3683UCUGGACUCUGAUGAGXCGAAAAGAGUAC4462GTACTCTTCAGTCCAGA1580HU MTR211 3684AUGAUCUGCUGAUGAGXCGAAACUGAAGA4463TCTICAGTCCAGATCAT1584HU MTR211 3685GCUUGGAUCUGAUGAGXCGAAAUCUGGAC4464GTCCAGATCATCCAAGC1590HU MTR211 3686UAGGCUUGCUGAUGAGXCGAAAUGAUCUG4465CAGATCATCCAAGCCTA1593HU MTR211 3687AUGUUUUCCUGAUGAGXCGAAAGGCUUGG4466CCAAGCCTAGAAAACAT1601HU MTR211 1619 AAUUUCUCCUGAUGAGXCGAAAUCAGUUC4467GAACTGATAGAGAAATT3688 3689UUUCCUGACUGAUGAGXCGAAAUUUCUCU4468AGAGAAATTTCAGGAAA1627HU MTR211 3690UUUUCCUGCUGAUGAGXCGAAAAUUUCUC4469GAGAAATTTCAGGAAAA1628HU MTR211 1629 CUUUUCCUCUGAUGAGXCGAAAAAUUUCU4470AGAAATTTCAGGAAAAG3691 3692UUCCACAUCUGAUGAGXCGAAAGCCUUUU4471AAAAGGCTTATGTGGAA1641HU MTR211 3693AUUCCACACUGAUGAGXCGAAAAGCCUUU4472AAAGGCTTATGTGGAAT1642HU MTR211 3694AAUCUUGGCUGAUGAGXCGAAAUUCCACA4473TGTGGAATTCCAAGATT1651HU MTR211 3695UAAUCUUGCUGAUGAGXCGAAAAUUCCAC4474GTGGAATTCCAAGATTA1652HU MTR211 3696GGUUAUAUCUGAUGAGXCGAAAUCUUGGA4475TCCAAGATTATATAACC1659HU MTR211 3697UGGUUAUACUGAUGAGXCGAAAAUCUUGG4476CCAAGATTATATAACCA1660HU MTR211 3698UUUGGUUACUGAUGAGXCGAAAUAAUCUU4477AAGATTATATAACCAAA1662HU MTR211 3699GUUUUGGUCUGAUGAGXCGAAAUAUAAUC4478GATTATATAACCAAAAC1664HU MTR211 3700CAUCUGGACUGAUGAGXCGAAAUGUUUUG4479CAAAACATATCCAGATG1675HU MTR211 3701GUCAUCUGCUGAUGAGXCGAAAUAUGUUU4480AAACATATCCAGATGAC1677HU MTR211 3702AUAACCUGCUGAUGAGXCGAAAGGUGUCA4481TGACACCTACAGGTTAT1690HU MTR211 3703GUCUGGAUCUGAUGAGXCGAAACCUGUAG4482CTACAGGTTATCCAGAC1696HU MTR211 3704AGUCUGGACUGAUGAGXCGAAAACCUGUA4483TACAGGTTATCCAGACT1697HU MTR211 3705GUAGUCUGCUGAUGAGXCGAAAUAACCUG4484CAGGTTATCCAGACTAC1699HU MTR211 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3706CUGAGUAGCUGAUGAGXCGAAAGUCUGGA4485TCCAGACTACTACTCAG1706HU MTR211 3707AAUCUGAGCUGAUGAGXCGAAAGUAGUCU4486AGACTACTACTCAGATT1709HU MTR211 3708GGCAAUCUCUGAUGAGXCGAAAGUAGUAG4487CTACTACTCAGATTGCC1712HU MTR211 3709AAGCUGGCCUGAUGAGXCGAAAUCUGAGU4488ACTCAGATTGCCAGCTT1717HU MTR211 3710CAGUCUUACUGAUGAGXCGAAAGCUGGCA4489TGCCAGCTTTAAGACTG1725HU MTR211 3711UCAGUCUUCUGAUGAGXCGAAAAGCUGGC4490GCCAGCTTTAAGACTGA1726HU MTR211 1727 AUCAGUCUCUGAUGAGXCGAAAAAGCUGG4491CCAGCTTTAAGACTGAT3712 3713AGUGAUGGCUGAUGAGXCGAAAGCAUUCA4492TGAATGCTACCATCACT1743HU MTR211 3714UCUUCAGUCUGAUGAGXCGAAAUGGUAGC4493GCTACCATCACTGAAGA1748HU MTR211 1759 HUMTR211 3715 UGAAAAAC CUGAUGAG X CGAA AUUCUUCA 4494 TGAAGAAT T GTTTTTCA 3716CUUUGAAACUGAUGAGXCGAAACAAUUCU4495ACAATTGTTTTTCAAAG1762HU MTR211 3717CCUUUGAACUGAUGAGXCGAAAACAAUUC4496GAATTGTTTTTCAAAGG1763HU MTR211 3718ACCUUUGACUGAUGAGXCGAAAAACAAUU4497AATTGTTTTTCAAAGGT1764HU MTR211 3719GACCUUUGCUGAUGAGXCGAAAAAACAAU4498ATTGTTTTTCAAAGGTC1765HU MTR211 3720AGACCUUUCUGAUGAGXCGAAAAAAACAA4499TTGTTTTTCAAAGGTCT1766HU MTR211 3721GCCAAUGACUGAUGAGXCGAAACCUUUGA4500TCAAAGGTCTCATTGGC1773HU MTR211 1775 UUGCCAAUCUGAUGAGXCGAAAGACCUUU4501AAAGGTCCCATTGGCAA3722 1778 AUAUUGCCCUGAUGAGXCGAAAUGAGACC4502GGTCTCATTGGCAATAT3723 3724AAUUCGUACUGAUGAGXCGAAAUUGCCAA4503TTGGCAATATACGAATT1785HU MTR211 3725UCAAUUCGCUGAUGAGXCGAAAUAUUGCC4504GGCAATATACGAATTGA1787HU MTR211 1793 HUMTR211 3726 XCGAAAUUCGUAU4505ATACGAATTGACAGTGTCUGAUGAG 3727UGUGGGAUCUGAUGAGXCGAAACACUGUC4506GACAGTGTTATCCCACA1802HU MTR211 3728AUGUGGGACUGAUGAGXCGAAAACACUGU4507ACAGTGTTATCCCACAT1803HU MTR211 3729AUAUGUGGCUGAUGAGXCGAAAUAACACU4508AGTGTTATCCCACATAT1805HU MTR211 3730UUUCAAAACUGAUGAG1812HUMTR211 X 4509TCCCACATATTTTGAAAAUGUGGGA 3731AUUUUCAACUGAUGAGXCGAAAUAUGUGG4510CCACATATTTTGAAAAT1814HU MTR211 3732CAUUUUCACUGAUGAGXCGAAAAUAUGUG4511CACATATTTTGAAAATG1815HU MTR211 3733CCAUUUUCCUGAUGAGXCGAAAAAUAUGU4512ACATATTTTGAAAATGG1816HU MTR211 3734AGAGUUAUCUGAUGAGXCGAAAUCUGCAG4513CTGCAGATTATAACTCT1836HU MTR211 3735GAGAGUUACUGAUGAGXCGAAAAUCUGCA4514TGCAGATTATAACTCTC1837HU MTR211 3736UUGAGAGUCUGAUGAGXCGAAAUAAUCUC4515CAGATTATAACTCTCAA1839HU MTR211 3737UUAUUUGACUGAUGAGXCGAAAGUUAUAA4516TTATAACTCTCAAATAA1843HU MTR211 3738AAUUAUUUCUGAUGAGXCGAAAGAGUUAU4517ATAACTCTCAAATAATT1845HU MTR211 3739UGACCAAUCUGAUGAGXCGAAAUUUGAGA4518TCTCAAATAATTGGTCA1850HU MTR211 3740CUGUGACCCUGAUGAGXCGAAAUUAUUUG4519CAAATAATTGGTCACAG1853HU MTR211 3741AAUGCUGUCUGAUGAGXCGAAACCAAUUA4520TAATTGGTCACAGCATT1857HU MTR211 3742AGUUUUCACUGAUGAGXCGAAAUGCUGUG4521CACAGCATTTGAAAACT1865HU MTR211 3743CAGUUUUCCUGAUGAGXCGAAAAUGCUGU4522ACAGCATTTGAAAACTG1866HU MTR211 3744GUUAAGUUCUGAUGAGXCGAAACAGCACU4523AGTGCTGTAAACTTAAC1890HU MTR211 3745GAACAGUUCUGAUGAGXCGAAAGUUUACA4524TGTAAACTTAACTGTTC1895HU MTR211 3746AGAACAGUCUGAUGAGXCGAAAAGUUUAC4525GTAAACTTAACTGTTCT1896HU MTR211 3747UGGCAAAGCUGAUGAGXCGAAACAGUUAA4526TTAACTGTTCTTTGCCA1902HU MTR211 3748CUGGCAAACUGAUGAGXCGAAAACAGUUA4527TAACTGTTCTTTGCCAG1903HU MTR211 3749UUCUGGCACUGAUGAGXCGAAAGAACAGU4528ACTGTTCTTTGCCAGAA1905HU MTR211 3750GUUCUGGCCUGAUGAGXCGAAAAGAACAG4529CTGTTCTTTGCCAGAAC1906HU MTR211 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-1 I Orphan Receptor Genes 3751GUGAGUUCCUGAUGAGXCGAAAUUUGGUG4530CACCAAATTGAACTCAC1929HU MTR211 3752AAAGCAGUCUGAUGAGXCGAAAGUUCAAU4531ATTGAACTCACTGCTTT1935HU MTR211 3753UGCCUCAACUGAUGAGXCGAAAGCAGUGA4532TCACTGCTTTTGAGGCA1942HU MTR211 3754AUGCCUCACUGAUGAGXCGAAAAGCAGUG4533CACTGCTTTTGAGGCAT1943HU MTR211 3755GAUGCCUCCUGAUGAGXCGAAAAAGCAGU4534ACTGCTTTTGAGGCATC1944HU MTR211 3756AAUUUCCACUGAUGAGXCGAAAUGCCUCA4535TGAGGCATCTGGAAATT1952HU MTR211 1960 AAAGUAAACUGAUGAGXCGAAAUUUCCAG4536CTGGAAATTTTTACTTT3757 3758UAAAGUAACUGAUGAGXCGAAAAUUUCCA4537TGGAAATTTTTACTTTA1961HU MTR211 1962 UUAAAGUACUGAUGAGXCGAAAAAUUUCC4538GGAAATTTTTACTTTAA3759 3760UUUAAAGUCUGAUGAGXCGAAAAAAUUUC4539GAAATTTTTACTTTAAA1963HU MTR211 1964 UUUUAAAGCUGAUGAGXCGAAAAAAAUUU4540AAATTTTTACTTTAAAA3761 3762ACUUUUUACUGAUGAGXCGAAAGUAAAAA4541TTTTTACTTTAAAAAGT1967HU MTR211 3763UACUUUUUCUGAUGAGXCGAAAAGUAAAA4542TTTTACTTTAAAAAGTA1968HU MTR211 3764UUACUUUUCUGAUGAGXCGAAAAAGUAAA4543TTTACTTTAAAAAGTAA1969HU MTR211 3765AUUCUGGUCUGAUGAGXCGAAACUUUUUA4544TAAAAAGTAACCAGAAT1976HU MTR211 3766AUACCUUGCUGAUGAGXCGAAAUUCUGGU4545ACCAGAATCCAAGGTAT1985HU MTR211 3767AAUAAAAACUGAUGAGXCGAAACCUUGGA4546TCCAAGGTATTTTTATT1992HU MTR211 3768AAAAUAAACUGAUGAGXCGAAAUACCUUG4547CAAGGTATTTTTATTTT1994HU MTR211 3769UAAAAUAACUGAUGAGXCGAAAAUACCUU4548AAGGTATTTTTATTTTA1995HU MTR211 3770CUAAAAUACUGAUGAGXCGAAAAAUACCU4549AGGTATTTTTATTTTAG1996HU MTR211 3771GCUAAAAUCUGAUGAGXCGAAAAAAUACC4550GGTATTTTTATTTTAGC1997HU MTR211 1998 AGCUAAAACUGAUGAGXCGAAAAAAAUAC4551GTATTTTTATTTTAGCT3772 3773GAAGCUAACUGAUGAGXCGAAAUAAAAAU4552ATTTTTATTTTAGCTTC2000HU MTR211 3774GGAAGCUACUGAUGAGXCGAAAAUAAAAA4553TTTTTATTTTAGCTTCC2001HU MTR211 3775GGGAAGCUCUGAUGAGXCGAAAAAUAAAA4554TTTTATTTTAGCTTCCC2002HU MTR211 3776AGGGAAGCCUGAUGAGXCGAAAAAAUAAA4555TTTATTTTAGCTTCCCT2003HU MTR211 3777CUUAAGGGCUGAUGAGXCGAAAGCUAAAA4556TTTTAGCTTCCCTTAAG2007HU MTR211 3778UCUUAAGGCUGAUGAGXCGAAAAGCUAAA4557TTTAGCTTCCCTTAAGA2008HU MTR211 3779AAAUUCUUCUGAUGAGXCGAAAGGGAAGC4558GCTTCCCTTAAGAATTT2012HU MTR211 3780AAAAUUCUCUGAUGAGXCGAAAAGGGAAG4559CTTCCCTTAAGAATTTT2013HU MTR211 3781ACUUCAAACUGAUGAGXCGAAAUUCUUAA4560TTAAGAATTTTTGAAGT2019HU MTR211 3782CACUUCAACUGAUGAGXCGAAAAUUCUUA4561TAAGAATTTTTGAAGTG2020HU MTR211 3783UCACUUCACUGAUGAGXCGAAAAAUUCUU4562AAGAATTTTTGAAGTGA2021HU MTR211 3784GUCACUUCCUGAUGAGXCGAAAAAAUUCU4563AGAATTTTTGAAGTGAC2022HU MTR211 3785AUUCAUUUCUGAUGAGXCGAAAUUUCUGC4564GCAGAAATTAAATGAAT2049HU MTR211 3786AAUUCAUUCUGAUGAGXCGAAAAUUUCUG4565CAGAAATTAAATGAATT2050HU MTR211 3787GGAAGAAACUGAUGAGXCGAAAUUCAUUU4566AAATGAATTTTTCTTCC2058HU MTR211 3788AGGAAGAACUGAUGAGXCGAAAAUUCAUU4567AATGAATTTTTCTTCCT2059HU MTR211 3789CAGGAAGACUGAUGAG2060HUMTR211 X 4568ATGAATTTTTCTTCCTGAAAUUCAU 3790UCAGGAAGCUGAUGAGXCGAAAAAAUUCA4569TGAATTTTTCTTCCTGA2061HU MTR211 3791AUCAGGAACUGAUGAGXCGAAAAAAAUUC4570GAATTTTTCTTCCTGAT2062HU MTR211 3792GAAUCAGGCUGAUGAGXCGAAAGAAAAAU4571ATTTTTCTTCCTGATTC2064HU MTR211 3793GGAAUCAGCUGAUGAGXCGAAAAGAAAAA4572TTTTTCTTCCTGATICC2065HU MTR211 3794UUUAAAGGCUGAUGAGXCGAAAUCAGGAA4573TTCCTGATTCCTTTAAA2071HU MTR211 2072 AUUUAAAGCUGAUGAGXCGAAAAUCAGGA4574TCCTGATTCCTTTAAAT3795 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3796UUCAUUUACUGAUGAGXCGAAAGGAAUCA4575TGATTCCTTTAAATGAA2075HU MTR211 3797AUUCAUUUCUGAUGAGXCGAAAAGGAAUC4576GATTCCTTTAAATGAAT2076HU MTR211 3798UAUUCAUUCUGAUGAGXCGAAAAAGGAAU4577ATTCCTTTAAATGAATA2077HU MTR211 3799GUGUUUCACUGAUGAGXCGAAAUUCAUUU4578AAATGAATATGAAACAC2085HU MTR211 3800UAAAUUUGCUGAUGAGXCGAAAGUGUUUC4579GAAACACTACAAATTTA2095HU MTR211 3801CAAGAAUACUGAUGAGXCGAAAUUUGUAG4580CTACAAATTTATTCTTG2101HU MTR211 3802CCAAGAAUCUGAUGAGXCGAAAAUUUGUA4581TACAAATTTATTCTTGG2102HU MTR211 3803ACCAAGAACUGAUGAGXCGAAAAAUUUGU4582ACAAATTTATTCTTGGT2103HU MTR211 3804UCACCAAGCUGAUGAGXCGAAAUAAAUUU4583AAATTTATTCTTGGTGA2105HU MTR211 3805UUCACCAACUGAUGAGXCGAAAAUAAAUU4584AATTTATTCTTGGTGAA2106HU MTR211 3806UCUUCACCCUGAUGAGXCGAAAGAAUAAA4585TTTATTCTTGGTGAAGA2108HU MTR211 2121 HUMTR211 3807 GCUUCAGG CUGAUGAG X CGAA AUCAUCUU 4586 AAGATGAT A CCTGAAGC 2133 HUMTR211 3808 CAAGAGGU CUGAUGAG X CGAA ACAGCUUC 4587 GAAGCTGT C ACCTCTTG 2138 HUMTR211 3809 AUAAUCAA CUGAUGAG X CGAA AGGUGACA 4588 TGTCACCT C TTGATTAT 2140 HUMTR211 3810 AGAUAAUC CUGAUGAG X CGAA AGAGGUGA 4589 TCACCTCT T GATTATCT 2144 HUMTR211 3811 GUUUAGAU CUGAUGAG X CGAA AUCAAGAG 4590 CTCTTGAT T ATCTAAAC 2145 HUMTR211 3812 AGUUUAGA CUGAUGAG X CGAA AAUCAAGA 4591 TCTTGATT A TCTAAACT 3813UUAGUUUACUGAUGAGXCGAAAUAAUCAA4592TTGATTATCTAAACTAA2147HU MTR211 3814GCUUAGUUCUGAUGAGXCGAAAGAUAAUC4593GATTATCTAAACTAAGC2149HU MTR211 3815UGAGCGCUCUGAUGAGXCGAAAGUUUAGA4594TCTAAACTAAGCGCTCA2154HU MTR211 3816AAUAGAAUCUGAUGAGXCGAAAGCGCUUA4595TAAGCGCTCATTCTATT2161HU MTR211 3817UAAAAUAGCUGAUGAGXCGAAAUGAGCGC4596GCGCTCATTCTATTTTA2164HU MTR211 3818AUAAAAUACUGAUGAGXCGAAAAUGAGCG4597CGCTCATTCTATTTTAT2165HU MTR211 2167 HUMTR211 3819 UUAUAAAA CUGAUGAG X CGAA AGAAUGAG 4598 CTCATTCT A TTTTATAA 2169 HUMTR211 3820 UUUUAUAA CUGAUGAG X CGAA AUAGAAUG 4599 CATTCTAT T TTATAAAA 2170 HUMTR211 3821 GUUUUAUA CUGAUGAG X CGAA AAUAGAAU 4600 ATTCTATT T TATAAAAC 2171 HUMTR211 3822 UGUUUUAU CUGAUGAG X CGAA AAAUAGAA 4601 TTCTATTT T ATAAAACA 2172 HUMTR211 3823 UUGUUUUA CUGAUGAG X CGAA AAAAUAGA 4602 TCTATTTT A TAAAACAA 2174 HUMTR211 3824 AUUUGUUU CUGAUGAG X CGAA AUAAAAUA 4603 TATTTTAT A AAACAAAT 2183 HUMTR211 3825 GACUAAUU CUGAUGAG X CGAA AUUUGUUU 4604 AAACAAAT A AATTAGTC 2187 HUMTR211 3826 AAGAGACU CUGAUGAG X CGAA AUUUAUUU 4605 AAATAAAT T AGTCTCTT 2188 HUMTR211 3827 AAAGAGAC CUGAUGAG X CGAA AAUUUAUU 4606 AATAAATT A GTCTCTTT 2191 HUMTR211 3828 AAAAAAGA CUGAUGAG X CGAA ACUAAUUU 4607 AAATTAGT C TCTTTTTT 2193 HUMTR211 3829 AGAAAAAA CUGAUGAG X CGAA AGACUAAU 4608 ATTAGTCT C TTTTTTCT 15 HUMTR29 3830 AGAAAGCC CUGAUGAG X CGAA ACGGGCCC 4609 GGGCCCGT C GGCTTTCT 20 HUMTR29 3831 GUUGAAGA CUGAUGAG X CGAA AGCCGACG 4610 CGTCGGCT T TCTTCAAC 21 HUMTR29 3832 GGUUGAAG CUGAUGAG X CGAA AAGCCGAC 4611 GTCGGCTT T CTTCAACC 22 HUMTR29 3833 GGGUUGAA CUGAUGAG X CGAA AAAGCCGA 4612 TCGGCTTT C TTCAACCC 24 HUMTR29 3834 GAGGGUUG CUGAUGAG X CGAA AGAAAGCC 4613 GGCTTTCT T CAACCCTC 25 HUMTR29 3835 AGAGGGUU CUGAUGAG X CGAA AAGAAAGC 4614 GCTTTCTT C AACCCTCT 32 HUMTR29 3836 CGGGAAGA CUGAUGAG X CGAA AGGGUUGA 4615 TCAACCCT C TCTTCCCG 34 HUMTR29 3837 UCCGGGAA CUGAUGAG X CGAA AGAGGGUU 4616 AACCCTCT C TTCCCGGA 36 HUMTR29 3838 GCUCCGGG CUGAUGAG X CGAA AGAGAGGG 4617 CCCTCTCT T CCCGGAGC 37 HUMTR29 3839 CGCUCCGG CUGAUGAG X CGAA AAGAGAGG 4618 CCTCTCTT C CCGGAGCG 54 HUMTR29 3840 CACUCGUG CUGAUGAG X CGAA AUUGGGGG 4619 CCCCCAAT C CACGAGIG Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3841GCCGACGCCUGAUGAGXCGAAACAGUCCC4620GGGACTGTCGCGTCGGC79HUMI R29 84 CGGGCGCCCUGAUGAGXCGAAACGCGACA4621TGTCGCGTCGGCGCCCG3842 102 CCCCUGCUCUGAUGAGXCGAAACUCCGCG4622CGCGGAGTCAGCAGGGG3843 3844CCAUGAURCUGAUGAGXCGAAACCGCUUU4623AAAGCGGTAGATCATGG122HUM IR29 3845GUUGCCAUCUGAUGAGXCGAAAUCUACCG4624CGGTAGATCATGGCAAC126HUM IR29 3846AUUUCUUCCUGAUGAGXCGAAAUGGUUGC4625GCAACCATAGAAGAAAT138HUM IR29 3847UGAUGUGCCUGAUGAGXCGAAAUUUCUUC4626GAAGAAATTGCACATCA147HUM IR29 3848AAUAAUUUCUGAUGAGXCGAAAUGUGCAA4627TTGCACATCAAATTATT154HUM IR29 159 HUMTR29 3849 UGUUCAAU CUGAUGAG X CGAA AUUUGAUG 4628 CATCAAAT T ATTGAACA 160 UUGUUCAACUGAUGAGXCGAAAAUUUGAU4629ATCAAATTATTGAACAA3850 3851UGUUGUUCCUGAUGAGXCGAAAUAAUUUG4630CAAATTATTGAACAACA162HUM IR29 3852UCUGUAACCUGAUGAGXCGAAAUCUCUCC4631GGAGAGATTGTTACAGA183HUM IR29 186 UGCUCUGUCUGAUGAGXCGAAACAAUCUC4632GAGATTGTTACAGAGCA3853 3854CUGCUCUGCUGAUGAGXCGAAAACAAUCU4633AGATTGTTACAGAGCAG187HUM IR29 3855ACAAUCUGCUGAUGAGXCGAAAUUUUCUG4634CAGAAAATCCAGATTGT213HUM IR29 219 HUMIR29 3856 XCGAAAUCUGGAU4635ATCCAGATTGTGACAGCCUGAUGAG 3857UUAUGAUCCUGAUGAGXCGAAAGUGCUGU4636ACAGCACTTGATCATAA231HUM IR29 3858GGUAUUAUCUGAUGAGXCGAAAUCAAGUG4637CACTTGATTATAATACC235HUM IR29 3859UUGGGUAUCUGAUGAGXCGAAAUGAUCAA4638TTGATCATAATACOCAA238HUM IR29 3860GCCUUGGGCUGAUGAGXCGAAAUUAUGAU4639ATCATAATACCCAAGGC241HUM IR29 3861UCAGAAUGCUGAUGAGXCGAAACUGCUUG4640CAAGCAGTTCATTCTGA257HUM IR29 3862GUCAGAAUCUGAUGAGXCGAAAACUGCUU4641AAGCAGTTCATTCTGAC258HUM IR29 3863UUUGUCAGCUGAUGAGXCGAAAUGAACUG4642CAGTTCATTCTGACAAA261HUM IR29 3864AUUUGUCACUGAUGAGXCGAAAAUGAACU4643AGTTCATTCTGACAAAT262HUM IR29 3865GCCGUCGUCUGAUGAGXCGAAAUUUGUCA4644TGACAAATCACGACGGC271HUM IR29 3866UUGGAGUACUGAUGAGXCGAAAGCCGUCG4645CGACGGCTCTACTCCAA281HUM IR29 3867GCUUGGAGCUGAUGAGXCGAAAGAGCCGU4646ACGGCTCTACTCCAAGC283HUM IR29 3868UUUGCUUGCUGAUGAGXCGAAAGUAGAGC4647GCTCTACTCCAAGCAAA286HUM IR29 3869GCCAGAAUCUGAUGAGXCGAAACUUUGCU4648AGCAAAGTCATTCTGGC297HUM IR29 3870CUGGCCAGCUGAUGAGXCGAAAUGACUUU4649AAAGTCATTCTGGCCAG300HUM IR29 3871CCUGGCCACUGAUAGAXCGAAAAUGACUU4650AAGTCATTCTGGCCAGG301HUM IR29 3872CGGAGUGGCUGAUGAGXCGAAAUCUUGCC4651GGCAAGATTCCACTCCG316HUM IR29 3873CCGGAGUGCUGAUGAGXCGAAAAUCUUGC4652GCAAGATTCCACTCCGG317HUM IR29 3874UUUUCCCGCUGAUGAGXCGAAAGUGGAAU4653ATTCCACTCCGGGAAAA322HUM IR29 333 HUMTR29 3875 GUAAGGAA CUGAUGAG X CGAA ACUUUUCC 4654 GGAAAAGT T TTCCTTAC 3876UGUAAGGACUGAUGAGXCGAAAACUUUUC4655GAAAAGTTTTCCTTACA334HUM IR29 3877UUGUAAGGCUGAUGAGXCGAAAAACUUUU4656AAAAGTTTTCCTTACAA335HUM IR29 336 GUUGUAAGCUGAUGAGXCGAAAAAACUUU4657AAAGTTTTCCTTACAAC3878 3879GGAGUUGUCUGAUGAGXCGAAAGGAAAAC4658GTTTTCCTTACAACTCC339HUM IR29 3880UGGAGUUGCUGAUGAGXCGAAAAGGAAAA4659TTTTCCTTACAACTCCA340HUM IR29 3881UGCAUCUGCUGAUGAGXCGAAAGUUGUAA4660TTACAACTCCAGATGCA346HUM IR29 3882AACUGGUUCUGAUGAGXCGAAACACCUGC4661GCAGGTGTCAACCAGTT363HUM IR29 3883UAAAAAAUCUGAUGAGXCGAAACUGGUUG4662CAACCAGTTATTTTTTA371HUM IR29 3884GUAAAAAACUGAUGAGXCGAAAACUGGUU4663AACCAGTTATTTTTTAC372HUM IR29 3885UGGUAAAACUGAUGAGXCGAAAUAACUGG4664CCAGTTATTTTTTACCA374HUM IR29 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 3886GUGGUAAACUGAUGAGXCGAAAAUAACUG4665CAGTTATTTTTTACCAC374HUM IR29 3887AGUGGUAACUGAUGAGXCGAAAAAUAACU4666AGTTATTTTTTACCACT376HUM IR29 3888GAGUGGUACUGAUGAGXCGAAAAAAUAAC4667GTTATTTTTTACCACTC377HUM IR29 3889GGAGUGGUCUGAUGAGXCGAAAAAAAUAA4668TTATTTTTTACCACTCC378HUM IR29 3890AGGAGUGGCUGAUGAGXCGAAAAAAAAUA4669TATTTTTTACCACTCCT379HUM IR29 3891CAGAUCAGCUGAUGAGXCGAAAGUGGUAA4670TTACCACTCCTGATCTG385HUM IR29 3892UGCAGACACUGAUGAGXCGAAAUCAGGAG4671CTCCTGATCTGTCTGCA391HUM IR29 3893GUUGUGCACUGAUGAGXCGAAACAGAUCA4672TGATCTGTCTGCACAAC395HUM IR29 3894UCUGUUAGCUGAUGAGXCGAAAGCUGCAG4673CTGCAGCTCCTAACAGA414HUM IR29 3895UUAUCUGUCUGAUGAGXCGAAAGGAGCUG4674CAGCTCCTAACAGATAA417HUM IR29 424 HUMIR29 3896 UGGAGAAU CUGAUGAG X CGAA AUCUGUUA 4675 TAACAGAT A ATTCTCCA 3897GUCUGGAGCUGAUGAGXCGAAAUUAUCUG4676CAGATAATTCTCCAGAC427HUM IR29 3898GGUCUGGACUGAUGAGXCGAAAAUUAUCU4677AGATAATTCTCCAGACC428HUM IR29 3899UUGGUCUGCUGAUGAGXCGAAAGAAUUAU4678ATAATTCTCCAGACCAA430HUM IR29 3900AAAAACCUCUGAUGAGXCGAAAUUUGGUC4679GACCAAATAAGGTTTTT448HUM IR29 3901AGAUCAAACUGAUGAGXCGAAACCUUAUU4680AATAAGGTTTTTGATCT453HUM IR29 3902AAGAUCAACUGAUGAGXCGAAAACCUUAU4681ATAAGGTTTTTGATCTT454HUM IR29 3903AAAGAUCACUGAUGAGXCGAAAAACCUUA4682TAAGGTTTTTGATCTTT455HUM IR29 3904CAAAGAUCCUGAUGAGXCGAAAAAACCUU4683AAGGTTTTTGATCTTTG456HUM IR29 3905UACGCAAACUGAUGAGXCGAAAUCAAAAA4684TTTTTGATCTTTGCGTA460HUM IR29 462462HUMIR29 3906 ACUACGCA CUGAUGAG X CGAA AGAUCAAA 4685 TTTGATCT T TGCGTAGT 463 HUMTR29 3907 UACUACGC CUGAUGAG X CGAA AAGAUCAA 4686 TTGATCTT T GCGTAGTA 468 HUMIR29 3908 CCACAUAC CUGAUGAG X CGAA ACGCAAAG 4687 CTTTGCGT A GTATGTGG 471 HUMIR29 3909 UCUCCACA CUGAUGAG X CGAA ACUACGCA 4688 TGCGTAGT A TGTGGAGA 488 HUMIR29 3910 GACGUCCU CUGAUGAG X CGAA AUGCUUUG 4689 CAAAGCAT C AGGACGTC 496 HUMIR29 3911 UCCAUAAU CUGAUGAG X CGAA ACGUCCUG 4690 CAGGACGT C ATTATGGA 499 HUMIR29 3912 UGCUCCAU CUGAUGAG X CGAA AUGACGUC 4691 GACGTCAT T ATGGAGCA 500 HUMIR29 3913 CUGCUCCA CUGAUGAG X CGAA AAUGACGU 4692 ACGTCATT A TGGAGCAG 510 HUMTR29 3914 UCACAAGU CUGAUGAG X CGAA ACUGCUCC 4693 GGAGCAGT A ACTTGTGA 514 HUMIR29 3915 GCCUUCAC CUGAUGAG X CGAA AGUUACUG 4694 CAGTAACT T GTGAAGGC 533 HUMIR29 3916 UUUUAAAA CUGAUGAG X CGAA AUCCUUUG 4695 CAAAGGAT T TTTTAAAA 534 HUMIR29 3917 CUUUUAAA CUGAUGAG X CGAA AAUCCUUU 4696 AAAGGATT T TTTAAAAG 535 HUMIR29 3918 UCUUUUAA CUGAUGAG X CGAA AAAUCCUU 4697 AAGGATTT T TTAAAAGA 536 HUMIR29 3919 UUCUUUUA CUGAUGAG X CGAA AAAAUCCU 4698 AGGATTTT T TAAAAGAA 537 HUMIR29 3920 CUUCUUUU CUGAUGAG X CGAA AAAAAUCC 4699 GGATTTTT T AAAAGAAG 538 HUMIR29 3921 GCUUCUUU CUGAUGAG X CGAA AAAAAAUC 4700 GATTTTTT A AAAGAAGC 549 HUMIR29 3922 UUUUUUCG CUGAUGAG X CGAA AUGCUUCU 4701 AGAAGCAT C CGAAAAAA 559 HUMIR29 3923 AUAUACUA CUGAUGAG X CGAA AUUUUUUC 4702 GAAAAAAT T TAGTATAT 560 HUMIR29 3924 AAUAUACU CUGAUGAG X CGAA AAUUUUUU 4703 AAAAAATT T AGTATATT 561 HUMIR29 3925 GAAUAUAC CUGAUGAG X CGAA AAAUUUUU 4704 AAAAATTT A GTATATTC 564 HUMIR29 3926 CAUGAAUA CUGAUGAG X CGAA ACUAAAUU 4705 AATTTAGT A TATTCATG 566 HUMIR29 3927 GACAUGAA CUGAUGAG X CGAA AUACUAAA 4706 TTTAGTAT A TTCATGTC 568 HUMIR29 3928 UCGACAUG CUGAUGAG X CGAA AUAUACUA 4707 TAGTATAT T CATGTCGA 569 HUMIR29 3929 CUCGACAU CUGAUGAG X CGAA AAUAUACU 4708 AGTATATT C ATGTCGAG 574 HUMIR29 3930 UGAUCCUC CUGAUGAG X CGAA ACAUGAAU 4709 ATTCATGT C GAGGATCA Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 581 AAUCCUUUCUGAUGAGXCGAAAUCCUCGA4710TCGAGGATCAAAGGATT3931 3932AAUAAUACCUGAUGAGXCGAAAUCCUUUG4711CAAAGGATTGTATTATT589HUM IR29 3933AUUAAUAACUGAUGAGXCGAAACAAUCCU4712AGGATTGTATTATTAAT592HUM IR29 3934UUAUUAAUCUGAUGAGXCGAAAUACAAUC4713GATTGTATTATTAATAA594HUM IR29 3935CUUAUUAACUGAUGAGXCGAAAAUACAAU4714ATTGTATTATTAATAAG595HUM IR29 3936UGCUUAUUCUGAUGAGXCGAAAUAAUACA4715TGTATTATTAATAAGCA597HUM IR29 3937GUGCUUAUCUGAUGAGXCGAAAAUAAUAC4716GTATTATTAATAAGCAC598HUM IR29 3938GUGGUGCUCUGAUGAGXCGAAAUUAAUAA4717TTATTAATAAGCACCAC601HUM IR29 3939GCAGUAUUCUGAUGAGXCGAAACAGCGGU4718ACCGCTGTCAATACTGC622HUM IR29 3940ACCUGCAGCUGAUGAGXCGAAAUUGACAG4719CTGTCAATACTGCAGGT626HUM IR29 3941AUCUCUGUCUGAUGAGXCGAAACCUGCAG4720CTGCAGGTTACAGAGAT635HUM IR29 3942CAUCUCUGCUGAUGAGXCGAAAACCUGCA4721TGCAGGTTACAGAGATG636HUM IR29 3943AAACGCAACUGAUGAGXCGAAACAUCUCU4722AGAGATGTATTGCGTTT646HUM IR29 648 HUMTR29 3944 CCAAACGC CUGAUGAG X CGAA AUACAUCU 4723 AGATGTAT T GCGTTTGG 3945UCAUUCCACUGAUGAGXCGAAACGCAAUA4724TATTGCGTTTGGAATGA653HUM IR29 3946UUCAUUCCCUGAUGAGXCGAAAACGCAAU4725ATTGCGTTTGGAATGAA654HUM IR29 3947AUUGGACACUGAUGAGXCGAAAGUCUUGC4726GCAAGACTCTGTCCAAT671HUM IR29 3948UCACAUUGCUGAUGAGXCGAAACAGAGUC4727GACTCTGTCCAATGTGA675HUM IR29 3949GAUACUUCCUGAUGAGXCGAAAUGGGUUU4728AAACCCATTGAAGTATC696HUM IR29 3950UCUCGUGACUGAUGAGXCGAAACUUCAAU4729ATTGAAGTATCACGAGA702HUM IR29 3951UUUCUCGUCUGAUGAGXCGAAAUACUUCA4730TGAAGTATCACGAGAAA704HUM IR29 3952AGUUGGAACUGAUGAGXCGAAAUUUUUCU4731AGAAAAATCTTCCAACT716HUM IR29 3953ACAGUUGGCUGAUGAGXCGAAAGAUUUUU4732AAAAATCTTCCAACTGT718HUM IR29 3954CACAGUUGCUGAUGAGXCGAAAAGAUUUU4733AAAATCTTCCAACTGTG719HUM IR29 3955UUCUGUUGCUGAUGAGXCGAAAGCGGCAC4734GTGCCGCTTCAACAGAA733HUM IR29 3956UUUCUGUUCUGAUGAGXCGAAAAGCGGCA4735TGCCGCTTCAACAGAAA734HUM IR29 3957CGGAUAUACUGAUGAGXCGAAAUUUUUUC4736GAAAAAATCTATATCCG747HUM IR29 3958UUCGGAUACUGAUGAGXCGAAAGAUUUUU4737AAAAATCTATATCCGAA749HUM IR29 3959CUUUCGGACUGAUGAGXCGAAAUAGAUUU4738AAATCTATATCCGAAAG751HUM IR29 3960UCCUUUCGCUGAUGAGXCGAAAUAUAGAU4739ATCTATATCCGAAAGGA753HUM IR29 3961GGGCUACGCUGAUGAGXCGAAAGGUCCUU4740AAGGACCTTCGTAGCCC765HUM IR29 3962UGGGCUACCUGAUGAGXCGAAAAGGUCCU4741AGGACCTTCGTAGCCCA766HUM IR29 3963UAAUGGGCCUGAUGAGXCGAAACGAAGGU4742ACCTTCGTAGCCCATTA769HUM IR29 3964UUGCAGUUCUGAUGAGXCGAAAUGGGCUA4743TAGCCCATTAACTGCAA776HUM IR29 3965GUUGCAGUCUGAUGAGXCGAAAAUGGGCU4744AGCCCATTAACTGCAAC777HUM IR29 3966AAAAGUUGCUGAUGAGXCGAAAGUUGCAG4745CTGCAACTCCAACTTTT787HUM IR29 3967UGUUACAACUGAUGAGXCGAAAGUUGGAG4746CTCCAACTTTTGTAACA793HUM IR29 3968CUGUUACACUGAUGAGXCGAAAAGUUGGA4747TCCAACTTTTGTAACAG794HUM IR29 3969UCUGUUACCUGAUGAGXCGAAAAAGUUGG4748CCAACTTTTGTAACAGA795HUM IR29 3970CUAUCUGUCUGAUGAGXCGAAACAAAAGU4749ACTTTTGTAACAGATAG798HUM IR29 3971ACUUUCACCUGAUGAGXCGAAAUCUGUUA4750TAACAGATAGTGAAAGT805HUM IR29 3972UGACCUUGCUGALGAGXCGAAACUUUCAC4751GTGAAAGTACAAGGTCA814HUM IR29 3973GUCCUGUUCUGAUGAGXCGAAACCUUGUA4752TACAAGGTCAACAGGAC821HUM IR29 3974CUGAAUCUCUGAUGAGXCGAAACAGUCCU4753AGGACTGTTAGATTCAG833HUM IR29 3975CCUGAAUCCUGAUGAGXCGAAAACAGUCC4754GGACTGTTAGATTCAGG834HUM IR29 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 838 CAUUCCUGCUGAUGAGXCGAAAUCUAACA4755TGTTAGATTCAGGAATG3976 3977ACAUUCCUCUGAUGAGXCGAAAAUCUAAC4756GTTAGATTCAGGAATGT839HUM IR29 3978UAUUCAUGCUGAUGAGXCGAAACAUUCCU4757AGGAATGTTCATGAATA848HUM IR29 849 AUAUUCAUCUGAUGAGXCGAAAACAUUCC4758GGAATGTTCATGAATAT3979 856 UGGAUGAACUGAUGAGXCGAAAUUCAUGA4759TCATGAATATTCATCCA3980 858 HUMTR29 3981 GAUGGAUG CUGAUGAG X CGAA AUAUUCAU 4760 ATGAATAT A CATCCATC 3982AGAUGGAUCUGAUGAGXCGAAAAUAUUCA4761TGAATATTCATCCATCT859HUM IR29 862 UCCAGAUGCUGAUGAGXCGAAAUGAAUAU4762ATATTCATCCATCTGGA3983 3984UUACUCCACUGAUGAGXCGAAAUGGAUGA4763TCATCCATCTGGAGTAA866HUM IR29 873 UCAGUUUUCUGAUGAGXCGAAACUCCAGA4764TCTGGAGTAAAAACTGA3985 3986GCACAGCUCUGAUGAGXCGAAACUCAGUU4765AACTGAGTCAGCTGTGC884HUM IR29 3987CCUUAUCUCUGAUGAGXCGAAAUGUCAUC4766GATGACATCAGATAAGG902HUM IR29 907 HUMIR29 3988 XCGAAAUCUGAUG4767CATCAGATAAGGCTGAACUGAUGAG 917 CCUGACAUCUGAUGAGXCGAAAUUCAGCC4768GGCTGAATCATGTCAGG3989 922 AUCUCCCUCUGAUGAGXCGAAACAUGAUU4769AATCATGTCAGGGAGAT3990 931 HUMIR29 3991 XCGAAAUCUCCCU4770AGGGAGATTTAAGTACACUGAUGAG 932 HUMIR29 3992 AUGUACUU CUGAUGAG X CGAA AAUCUCCC 4771 GGGAGATT T AAGTACAT 933 AAUGUACUCUGAUGAGXCGAAAAAUCUCC4772GGAGATTTAAGTACATT3993 937 HUMIR29 3994 GGCCAAUG CUGAUGAG X CGAA ACUUAAAU 4773 ATTTAAGT A CATTGGCC 941 HUMIR29 3995 CAUUGGCC CUGAUGAG X CGAA AUGUACUU 4774 AAGTACAT T GGCCAATG 954 HUMIR29 3996 AAUGAUGU CUGAUGAG X CGAA ACCACAUU 4775 AATGTGGT T ACATCATT 955 HUMIR29 3997 UAAUGAUG CUGAUGAG X CGAA AACCACAU 4776 ATGTGGTT A CATCATTA 959 HUMIR29 3998 UCGCUAAU CUGAUGAG X CGAA AUGUAACC 4777 GGTTACAT C ATTAGCGA 962 HUMIR29 3999 GAUUCGCU CUGAUGAG X CGAA AUGAUGUA 4778 TACATCAT T AGCGAATC 963 HUMIR29 4000 AGAUUCGC CUGAUGAG X CGAA AAUGAUGU 4779 ACATCATT A GCGAATCT 970 HUMIR29 4001 UUUUCCAA CUGAUGAG X CGAA AUUCGCUA 4780 TAGCGAAT C TTGGAAAA 972 HUMIR29 4002 GUUUUUCC CUGAUGAG X CGAA AGAUUCGC 4781 GCGAATCT T GGAAAAAC 982 HUMIR29 4003 AAGAUCUU CUGAUGAG X CGAA AGUUUUUC 4782 GAAAAACT A AAGATCTT 988 HUMIR29 4004 UUGAGAAA CUGAUGAG X CGAA AUCUUUAG 4783 CTAAAGAT C TTTCTCAA 990 HUMIR29 4005 UUUUGAGA CUGAUGAG X CGAA AGAUCUUU 4784 AAAGATCT T TCTCAAAA 4006AUUUUGAGCUGAUGAGXCGAAAAGAUCUU4785AAGATCTTTCTCAAAAT991HUM IR29 992 UAUUUUGACUGAUGAGXCGAAAAAGAUCU4786AGATCTTTCTCAAAATA4007 4008ACUAUUUUCUGAUGAGXCGAAAGAAAGAU4787ATCTTTCTCAAAATAGT994HUM IR29 4009UUCAUUACCUGAUGAGXCGAAAUUUUGAG4788CTCAAAATAGTAATGAA1000HU MIR29 1003 HUMIR29 4010 CAUUUCAU CUGAUGAG X CGAA ACUAUUUU 4789 AAAATAGT A ATGAAATG 1013 HUMIR29 4011 CAAUCAUA CUGAUGAG X CGAA ACAUUUCA 4790 TGAAATGT C TATGATTG 1015 HUMIR29 4012 UUCAAUCA CUGAUGAG X CGAA AGACAUUU 4791 AAATGTCT A TGATTGAA 1020 HUMIR29 4013 AAGCUUUC CUGAUGAG X CGAA AUCAUAGA 4792 TCTATGAT T GAAAGCTT 1028 HUMIR29 4014 CAUUGCUU CUGAUGAG X CGAA AGCUUUCA 4793 TGAAAGCT T AAGCAATG 1029 HUMIR29 4015 UCAUUGCU CUGAUGAG X CGAA AAGCUUUC 4794 GAAAGCTT A AGCAATGA 1042 HUMIR29 4016 CAAAGAGG CUGAUGAG X CGAA AUCAUCAU 4795 ATGATGAT A CCTCTTTG 1046 HUMIR29 4017 CACACAAA CUGAUGAG X CGAA AGGUAUCA 4796 TGATACCT C TTTGTGTG 1048 HUMIR29 4018 UUCACACA CUGAUGAG X CGAA AGAGGUAU 4797 ATACCTCT T TGTGTGAA 1049 HUMIR29 4019 AUUCACAC CUGAUGAG X CGAA AAGAGGUA 4798 TACCTCTT T GTGTGAAT 1058 HUMIR29 4020 UUUCUUGA CUGAUGAG X CGAA AUUCACAC 4799 GTGTGAAT T TCAAGAAA Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 4021AUUUCUUGCUGAUGAGXCGAAAAUUCACA4800TGTGAATTTCAAGAAAT1059HU MIR29 4022CAUUUCUUCUGAUGAGXCGAAAAAUUCAC4801GTGAATTTCAAGAAATG1060HU MIR29 1086 GCCCUUGACUGAUGAGXCGAAACAUCACC4802GGTGATGTTTCAAGGGC4023 4024UGCCCUUGCUGAUGAGXCGAAAACAUCAC4803GTGATGTTTCAAGGGCA1087HU MIR29 4025AUGCCCUUCUGAUGAGXCGAAAAACAUCA4804TGATGTTTCAAGGGCAT1088HU MIR29 4026GAGUGUCACUGAUGAGXCGAAAUGCCCUU4805AAGGGCATTTGACACTC1097HU MIR29 4027AGAGUGUCCUGAUGAGXCGAAAAUGCCCU4806AGGGCATTTGACACTCT1098HU MIR29 4028UUUUGCAACUGAUGAGXCGAAAGUGUCAA4807TTGACACTCTTGCAAAA1105HU MIR29 4029GCUUUUGCCUGAUGAGXCGAAAGAGUGUC4808GACACTCTTGCAAAAGC1107HU MIR29 4030CAGGAUUCCUGAUGAGXCGAAAUGCUUUU4809AAAAGCATTGAATCCTG1118HU MIR29 4031CUCUCCAGCUGAUGAGXCGAAAUUCAAUG4810CATTGAATCCTGGAGAG1123HU MIR29 4032CCGCUACUCUGAUGAGXCGAAAGCUCUGG4811CCAGAGCTCAGTAGCGG1151HU MIR29 4033AUGCCCGCCUGAUGAGXCGAAACUGAGCU4812AGCTCAGTAGCGGGCAT1155HU MIR29 4034AUUAGGUGCUGAUGAGXCGAAACACUUCC4813GGAAGTGTACACCTAAT1176HU MIR29 4035CCAGUGAUCUGAUGAGXCGAAAGGUGUAC4814GTACACCTAATCACTGG1182HU MIR29 4036UCUCCAGUCUGAUGAGXCGAAAUUAGGUG4815CACCTAATCACTGGAGA1185HU MIR29 4037UAUGCUUGCUGAUGAGXCGAAAUCUCCAG4816CTGGAGATTCAAGCATA1195HU MIR29 4038UUAUGCUUCUGAUGAGXCGAAAAUCUCCA4817TGGAGATTCAAGCATAA1196HU MIR29 4039GUGUAAUUCUGAUGAGXCGAAAUGCUUGA4818TCAAGCATAAATTACAC1203HU MIR29 1207 UUGCCUGUCUGAUGAGXCGAAAUUUAUGC4819GCATAAATAACACCGAA4040 4041UUUCGGUGCUGAUGAGXCGAAAAUUUAUG4820CATAAATTACACCGAAA1208HU MIR29 4042UCGCUGAGCUGAUGAGXCGAAAGUGGCCC4821GGGCCACTTCTCAGCGA1230HU MIR29 4043AUCGCUGACUGAUGAGXCGAAAAGUGGCC4822GGCCACTTCTCAGCGAT1231HU MIR29 4044GAAUCGCUCUGAUGAGXCGAAAGAAGUGG4823CCACTTCTCAGCGATTC1233HU MIR29 4045UACAUGUGCUGAUGAGXCGAAAUCGCUGA4824TCAGCGATTCACATGTA1240HU MIR29 1241 HUMIR29 4046 XCGAAAAUCGCUG4825CAGCGATTCACATGTAGCUGAUGAG 4047CUGAAAGCCUGAUGAGXCGAAACAUGUGA4826TCACATGTAGCTTTCAG1248HU MIR29 4048GAGCCUGACUGAUGAGXCGAAAGCUACAU4827ATGTAGCTTTCAGGCTC1252HU MIR29 4049UGAGCCUGCUGAUGAGXCGAAAAGCUACA4828TGTAGCTTTCAGGCTCA1253HU MIR29 4050GUGAGCCUCUGAUGAGXCGAAAAAGCUAC4829GTAGCTTTCAGGCTCAC1254HU MIR29 4051GGCAUGGUCUGAUGAGXCGAAAGCCUGAA4830TTCAGGCTCACCATGCC1260HU MIR29 4052CAUAGGAGCUGAUGAGXCGAAAGGCAUGG4831CCATGCCTTCTCCTATG1270HU MIR29 4053GCAUAGGACUGAUGAGXCGAAAAGGCAUG4832CATGCCTTTTCCTATGC1271HU MIR29 4054AGGCAUAGCUGAUGAGXCGAAAGAAGGCA4833TGCCTTCTCCTATGCCT1272HU MIR29 4055CUCAGGCA1276HUMIR29 CGAAAGGAGAAG4834CTTCTCCTATGCCTGAGX 1286 CAUUCAGGCUGAUGAGXCGAAACUCAGGC4835GCCTGAGTACCTGAATG4056 4057CCCCAAUGCUGAUGAGXCGAAAGUGCACA4836TGTGCACTACATTGGGG1301HU MIR29 4058GACUCCCCCUGAUGAGXCGAAAUGUAGUG4837CACTACATTGGGGAGTC1305HU MIR29 4059UGGAGGCACUGAUGAGXCGAAACUCCCCA4838TGGGGAGTCTGCCTCCA1313HU MIR29 4060GCAGUCUGCUGAUGAGXCGAAAGGCAGAC4839GTCTGCCTCCAGACTGC1319HU MIR29 4061UUGAUAAGCUGAUGAGXCGAAACAGCAGU4840ACTGCTGTTCTTATCAA1331HU MIR29 4062AUUGAUAACUGAUGAGXCGAAAACAGCAG4841CTGCTGTTCTTATCAAT1332HU MIR29 4063GCAUUGAUCUGAUGAGXCGAAAGAACAGC4842GCTGTTCTTATCAATGC1334HU MIR29 4064UGCAUUGACUGAUGAGXCGAAAAGAACAG4843CTGTTCTTATCAATGCA1335HU MIR29 4065AGUGCAUUCUGAUGAGXCGAAAUAAGAAC4844GTTCTTATCAATGCACT1337HU MIR29 Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 1353 GGAAUCGACUGAUGAGXCGAAAGUGCCCA4845TGGGCACTTTCGATTCC4066 4067AGGAAUCGCUGAUGAGXCGAAAAGUGCCC4846GGGCACTTTCGATTCCT1354HU MTR29 4068AAGGAAUCCUGAUGAGXCGAAAAAGUGCC4847GGCACTTTCGATTCCTT1355HU MTR29 4069AAAGAAGGCUGAUGAGXCGAAAUCGAAAG4848CTTTCGATTCCTTCTTT1359HU MTR29 4070GAAAGAAGCUGAUGAGXCGAAAAUCGAAA4849TTTCGATTCCTTCTTTC1360HU MTR29 4071CUGGAAAGCUGAUGAGXCGAAAGGAAUCG4850CGATTCCTTCTTTCCAG1363HU MTR29 4072CCUGGAAACUGAUGAGXCGAAAAGGAAUC4851GATTCCTTCTTTCCAGG1364HU MTR29 4073AGCCUGGACUGAUGAGXCGAAAGAAGGAA4852TTCCTTCTTTCCAGGCT1366HU MTR29 4074GAGCCUGGCUGAUGAGXCGAAAAGAAGGA4853TCCTTCTTTCCAGGCTC1367HU MTR29 4075AGAGCCUGCUGAUGAGXCGAAAAAGAAGG4854CCTTCTTTCCAGGCTCT1368HU MTR29 4076UUGCCCUACUGAUGAGXCGAAAGCCUGGA4855TCCAGGCTCTAGGGCAA1375HU MTR29 1377 HUMTR29 4077 UCUUGCCC CUGAUGAG X CGAA AGAGCCUG 4856 CAGGCTCT A GGGCAAGA 1395 HUMTR29 4078 ACCAGUGA CUGAUGAG X CGAA AUGCUGUU 4857 AACAGCAT A TCACTGGT 1397 HUMTR29 4079 UCACCAGU CUGAUGAG X CGAA AUAUGCUG 4858 CAGCATAT C ACTGGTGA 1411 HUMTR29 4080 AUUCCAGU CUGAUGAG X CGAA AGCUUUCA 4859 TGAAAGCT T ACTGGAAT 4081CAUUCCAGCUGAUGAGXCGAAAAGCUUUC4860GAAAGCTTACTGGAATG1412HU MTR29 1425 HUMTR29 4082 AGAGUAAA CUGAUGAG X CGAA AGUUCAUU 4861 AATGAACT T TTTACTCT 1426 HUMTR29 4083 AAGAGUAA CUGAUGAG X CGAA AAGUUCAU 4862 ATGAACTT T TTACTCTT 1427 HUMTR29 4084 CAAGAGUA CUGAUGAG X CGAA AAAGUUCA 4863 TGAACTTT T TACTCTTG 1428 HUMTR29 4085 CCAAGAGU CUGAUGAG X CGAA AAAAGUUC 4864 GAACTTTT T ACTCTTGG 1429 HUMTR29 4086 ACCAAGAG CUGAUGAG X CGAA AAAAAGUU 4865 AACTTTTT A CTCTTGGT 1432 HUMTR29 4087 AAGACCAA CUGAUGAG X CGAA AGUAAAAA 4866 TTTTTACT C TTGGTCTT 1434 HUMTR29 4088 GCAAGACC CUGAUGAG X CGAA AGAGUAAA 4867 TTTACTCT T GGTCTTGC 1438 HUMTR29 4089 CUGGGCAA CUGAUGAG X CGAA ACCAAGAG 4868 CTCTTGGT C TTGCCCAG 1440 HUMTR29 4090 CACUGGGC CUGAUGAG X CGAA AGACCAAG 4869 CTTGGTCT T GCCCAGTG 1467 HUMTR29 4091 AUAGUUGC CUGAUGAG X CGAA ACAUUCAU 4870 ATGAATGT A GCAACTAT 1474 HUMTR29 4092 UGCUAAUA CUGAUGAG X CGAA AGUUGCUA 4871 TAGCAACT A TATTAGCA 1476 HUMTR29 4093 GUUGCUAA CUGAUGAG X CGAA AUAGUUGC 4872 GCAACTAT A TTAGCAAC 1478 HUMTR29 4094 AUGUUGCU CUGAUGAG X CGAA AUAUAGUU 4873 AACTATAT T AGCAACAT 1479 HUMTR29 4095 AAUGUUGC CUGAUGAG X CGAA AAUAUAGU 4874 ACTATATT A GCAACATT 1487 HUMTR29 4096 AAUUGACA CUGAUGAG X CGAA AUGUUGCU 4875 AGCAACAT T TGTCAATT 1488 HUMTR29 4097 CAAUUGAC CUGAUGAG X CGAA AAUGUUGC 3876 GCAACATT T GTCAATTG 1491 HUMTR29 4098 AGACAAUU CUGAUGAG X CGAA ACAAAUGU 4877 ACATTTGT C AATTGTCT 1495 HUMTR29 4099 GUGAAGAC CUGAUGAG X CGAA AUUGACAA 4878 TTGTCAAT T GTCTTCAC 1498 HUMTR29 4100 AUUGUGAA CUGAUGAG X CGAA ACAAUUGA 4879 TCAATTGT C TTCACAAT 1500 HUMTR29 4101 CUAUUGUG CUGAUGAG X CGAA AGACAAUU 4880 AATTGTCT T CACAATAG 1501 HUMTR29 4102 ACUAUUGU CUGAUGAG X CGAA AAGACAAU 4881 ATTGTCTT C ACAATAGT 1507 HUMTR29 4103 UUGAAGAC CUGAUGAG X CGAA AUUGUGAA 4882 TTCACAAT A GTCTTCAA 1510 HUMTR29 4104 UUGUUGAA CUGAUGAG X CGAA ACUAUUGU 4883 ACAATAGT C TTCAACAA 1512 HUMTR29 4105 GCUUGUUG CUGAUGAG X CGAA AGACUALU 4884 AATAGTCT T CAACAAGC 1513 HUMTR29 4106 UGCUUGUU CUGAUGAG X CGAA AAGACUAU 4885 ATAGTCTT C AACAAGCA 1529 HUMTR29 4107 AAGGUGAU CUGAUGAG X CGAA ACCCCUCU 4886 AGAGGGGT A ATCACCTT 1532 HUMTR29 4108 UUUAAGGU CUGAUGAG X CGAA AUUACCCC 4887 GGGGTAAT C ACCTTAAA 1537 HUMTR29 4109 GACAUUUU CUGAUGAG X CGAA AGGUGAUU 4888 AATCACCT T AAAATGTC 1538 HUMTR29 4110 UGACAUUU CUGAUGAG X CGAA AAGGUGAU 4889 ATCACCTT A AAATGTCA Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 4111UUUUUGAUCUGAUGAGXCGAAACAUUUUA4890TAAAATGTCATCAAAAA1545HU MTR29 4112CUAUUUUUCUGAUGAGXCGAAAUGACAUU4891AATGTCATCAAAAATAG1548HU MTR29 4113AGUAGAUCCUGAUGAGXCGAAAUUUUUGA4892TCAAAAATAGATCTACT1555HU MTR29 4114UUCUAGUACUGAUGAGXCGAAAUCUAUUU4893AAATAGATCTACTAGAA1559HU MTR29 4115CCUUCUAGCUGAUGAGXCGAAAGAUCUAU4894ATAGATCTACTAGAAGG1561HU MTR29 4116CUGCCUUCCUGAUGAGXCGAAAGUAGAUC4895GATCTACTAGAAGGCAG1564HU MTR29 4117GGGAAUGUCUGAUGAGXCGAAAUGCUGCC4896GGCAGCATCACATTCCC1576HU MTR29 4118AAGAUGGGCUGAUGAGXCGAAAUGUGAUG3897CATCACATTCCCATCTT1581HU MTR29 4119UAAGAUGGCUGAUGAGXCGAAAAUGUGAU4898ATCACATTCCCATCTTA1582HU MTR29 4120AUAAGUAACUGAUGAGXCGAAAUGGGAAU4899ATTCCCATCTTACTTAT1587HU MTR29 4121CCAUAAGUCUGAUGAGXCGAAAGAUGGGA4900TCCCATCTTACTTATGG1589HU MTR29 4122UCCAUAAGCUGAUGAGXCGAAAAGAUGGG4901CCCATCTTACTTATGGA1590HU MTR29 4124GGAGUCCACUGAUGAGXCGAAAAGUAAGA4903TCTTACTTATGGACTCC1594HU MTR29 1601 AGGGGUAGCUGAUGAGXCGAAAGUCCAUA4904TATGGACTCCTACCCCT4125 4126ACCAGGGGCUGAUGAGXCGAAAGGAGUCC4905GGACTCCTACCCCTGGT1604HU MTR29 4127AAGACAUGCUGAUGAGXCGAAACCAGGGG4906CCCCTGGTTCATGTCTT1613HU MTR29 1614 UAAGACAUCUGAUGAGXCGAAAACCAGGG4907CCCTGGTTCATGTCTTA4128 4129GCAUAUAACUGAUGAGXCGAAACAUGAAC4908GTTCATGTCTTATATGC1619HU MTR29 1621 HUMTR29 4130 AGGCAUAU CUGAUGAG X CGAA AGACAUGA 4909 TCATGTCT T ATATGCCT 1622 HUMTR29 4131 CAGGCAUA CUGAUGAG X CGAA AAGACAUD 4910 CATGTCTT A TATGCCTG 1624 HUMTR29 4132 UACAGGCA CUGAUGAG X CGAA AUAAGACA 4911 TGTCTTAT A TGCCTGTA 1632 HUMTR29 4133 AUAACCAU CUGAUGAG X CGAA ACAGGCAU 4912 ATGCCTGT A ATGGTTAT 1638 HUMTR29 4134 GGCUUUAU CUGAUGAG X CGAA ACCAUUAC 4913 GTAATGGT T ATAAAGCC 1639 HUMTR29 4135 AGGCUUUA CUGAUGAG X CGAA AACCAUUA 4914 TAATGGTT A TAAAGCCT 1641 HUMTR29 4136 GUAGGCUU CUGAUGAG X CGAA AUAACCAU 4915 ATGGTTAT A AAGCCTAC 1648 HUMTR29 4137 CCUGAAGG CUGAUGAG X CGAA AGGCUUUA 4916 TAAAGCCT A CCTTCAGG 1652 HUMTR29 4138 CUUUCCUG CUGAUGAG X CGAA AGGUAGGC 4917 GCCTACCT T CAGGAAAG 1653 HUMTR29 4139 GCUUUCCU CUGAUGAG X CGAA AAGGUAGG 4918 CCTACCTT C AGGAAAGC 1663 HUMTR29 4140 GUCAACCA CUGAUGAG X CGAA AGCUUUCC 4919 GGAAAGCT A TGGTTGAC 1668 HUMTR29 4141 AAUUAGUC CUGAUGAG X CGAA ACCAUAGC 4920 GCTATGGT T GACTAATT 1673 HUMTR29 4142 UUAGUAAU CUGAUGAG X CGAA AGUCAACC 4921 GGTTGACT A ATTACTAA 1676 HUMTR29 4143 CCAUUAGU CUGAUGAG X CGAA AUUAGUCA 4922 TGACTAAT T ACTAATCG 1677 HUMTR29 4144 UCCAUUAG CUGAUGAG X CGAA AAUUAGUC 4923 GACTAATT A CTAATGGA 1680 HUMTR29 4145 CCAUCCAU CUGAUGAG X CGAA AGUAAUUA 4924 TAATTACT A ATGGATGG 1691 HUMTR29 4146 AUGUUUAA CUGAUGAG X CGAA ACCCAUCC 4925 GGATGGGT T TTAAACAT 1692 HUMTR29 4147 CAUGUUUA CUGAUGAG X CGAA AACCCAUC 4926 GATGGGTT T TAAACATG 1693 HUMTR29 4148 ACAUGUUU CUGAUGAG X CGAA AAACCCAU 4927 ATGGGTTT T AAACATGT 1694 HUMTR29 4149 GACAUGUU CUGAUGAG X CGAA AAAACCCA 4928 TGGGTTTT A AACATGTC 1702 HUMTR29 4150 UGUAGAGG CUGAUGAG X CGAA ACAUGUUU 4929 AAACATGT C CCTCTACA 1706 HUMTR29 4151 UUAUUGUA CUGAUGAG X CGAA AGGGACAU 4930 ATGTCCCT C TACAATAA 1708 HUMTR29 4152 AUUUAUUG CUGAUGAG X CGAA AGAGGGAC 4931 GTCCCTCT A CAATAAAT 1713 HUMTR29 4153 UUUUAAUU CUGAUGAG X CGAA AUUGUAGA 4932 TCTACAAT A AATTAAAA 1717 HUMTR29 4154 AAGAUUUU CUGAUGAG X CGAA AUUUAUUG 4933 CAATAAAT T AAAATCTT 1718 HUMTR29 4155 AAAGAUUU CUGAUGAG X CGAA AAUUUAUU 4934 AATAAATT A AAATCTTT Table IV. Hammerhead Ribozymes to TR2-9 and TR2-11 Orphan Receptor Genes 4156CAUUGAAACUGAUGAGXCGAAAUUUUAAU4935ATTAAAATCTTTCAATG1723HU MTR29 4157AACAUUGACUGAUGAGXCGAAAGAUUUUA4936TAAAATCTTTCAATGTT1725HU MTR29 4158AAACAUUGCUGAUGAGXCGAAAAGAUUUU4937AAAATCTTTCAATGTTT1726HU MTR29 4159CAAACAUUCUGAUGAGXCGAAAAAGAUUU4938AAATCTTTCAATGTTTG1727HU MTR29 1733 UAUAUUCACUGAUGAGXCGAAACAUUGAA4939TTCAATGTTTGAATATA4160 4161UUAUAUUCCUGAUGAGXCGAAAACAUUGA4940TCAATGTTTGAATATAA1734HU MTR29 4162CCACAUUACUGAUGAGXCGAAAUUCAAAC4941GTTTGAATATAATGTGG1739HU MTR29 4163CUCCACAUCUGAUGAGXCGAAAUAUUCAA4942TTGAATATAATGTGGAG1741HU MTR29 4164CUCAGGUACUGAUGAGXCGAAACACCUCC4943GGAGGTGTTTACCTGAG1754HU MTR29 4165CCUCAGGUCUGAUGAGXCGAAAACACCUC4944GAGGTGTTTACCTGAGG1755HU MTR29 4166CCCUCAGGCUGAUGAGXCGAAAAACACCU4945AGGTGTTTACCTGAGGG1756HU MTR29 4167GAGAUAGACUGAUGAGXCGAAAGGCCCUC4946GAGGGCCTCTCTATCTC1768HU MTR29 4168GGGAGAUACUGAUGAGXCGAAAGAGGCCC4947GGGCCTCTCTATCTCCC1770HU MTR29 1772 CGGGGAGACUGAUGAGXCGAAAGAGAGGC4948GCCTCTCTATCTCCCCG4169 4170UUCGGGGACUGAUGAGXCGAAAUAGAGAG4949CTCTCTATCTCCCCGAA1774HU MTR29 4171AAUUCGGGCUGAUGAGXCGAAAGAUAGAG4950CTCTATCTCCCOGAATT1776HU MTR29 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.

Table V. Hammerhea, @ozymes to EAR3/COUP-TF-1 I.D.RZSeq.I.D.SubetratePcsSeq. No.No. 16 4951 XCGAAAUGGCACA5248TGTGCCATTTCTGATTTCUGAUGAG AAAAUCAGCUGAUGAGXCGAAAAUGGCAC5249GTGCCATTTCTGATTTT174952 CAAAAUCACUGAUGAGXCGAAAAAUGGCA5250TGCCATTTCTGATTTTG184953 AGUUGCAACUGAUGAGXCGAAAUCAGAAA5251TTTCTGATTTTGCAACT234954 AAGUUGCACUGAUGAGXCGAAAAUCAGAA5252TTCTGATTTTGCAACTT244955 CAAGUUGCCUGAUGAGXCGAAAAAUCAGA5253TCTGATTTTGCAACTTG254956 32 CUGAUGAGXCGAAAGUUGCAA5254TTGCAACTTGGGGAAGAUCUUCCCC CGGCGAGCCUGAUGAGXCGAAAGCUCCCU5255AGGGAGCTTGCTCGCCG654958 CCCCCGGCCUGAUGAGXCGAAAGCAAGCU5256AGCTTGCTCGCCGGGGG694959 CCCCCCCCCUGAUGAGXCGAAACACCCCU5257AGGGGTGTTGGGGGGGG1544960 275 4961 XCGAAACUGCCUC5258GAGGCAGTAGCGGCGGCCUGAUGAG CCGAGCCGCUGAUGAGXCGAAACACCGGC5259GCCGGTGTCCGGCTOGG3174962 323 4963CCGAGCCC CGAAAGCCGGAC5260GTCCGGCTCGGGCTOGGX CAGGAGOCCUGAUGAGXCGAAAGCCCGAG5261CTCGGGCTCGGCTCCTG3294964 GGUCGCAGCUGAUGAGXCGAAAGCCGAGC5262GCTCGGCTCCTGOGACC3344965 GGGAGGGGCUGAUGAGXCGAAAGGGGGCG5263CGCCCCCTCCCCCTCCC3734966 379 4967 GAAGGGGG CUGAUGAG X CGAA AGGGGGAG 5264 CTCCCCCT C CCCCCTTC 386 4968 GGAAGGGG CUGAUGAG X CGAA AGGGGGGA 5265 TCCCCCCT T CCCCTTCC 387 4969 GGGAAGGG CUGAUGAG X CGAA AAGGGGGG 5266 CCCCCCTT C CCCTTCCC 392 4970 GGAAGGGG CUGAUGAG X CGAA AGGGGAAG 5267 CTTCCCCT T CCCCTTCC 393 4971 GGGAAGGG CUGAUGAG X CGAA AAGGGGAA 5268 TTCCCCTT C CCCTTCCC 398 4972 GGGAGGGG CUGAUGAG X CGAA AGGGGAAG 5269 CTTCCCCT T CCCCTCCC 399 4973 UGGGAGGG CUGAUGAG X CGAA AAGGGGAA 5270 TTCCCCTT C CCCTCCCA 404 4974 CGCGCUGG CUGAUGAG X CGAA AGGGGAAG 5271 CTTCCCCT C CCAGCGCG 433 4975 UGCUCGCC CUGAUGAG X CGAA AGGGCCGC 5272 GCGGCCCT C GGCGAGCA GGGGAGCCCUGAUGAGXCGAAAGCUGCUC5273GAGCAGCTCGGCTCCCC4454976 450 4977 GCUGGGGG CUGAUGAG X CGAA AGCCGAGC 5274 GCTCGGCT C CCCCCAGC GGCCCGGGCUGAUGAGXCGAAAGCGCUGG5275CCAGCGCTCCCCGGGCC4624978 CAUUGCCACUGAUGAGXCGAAAUCUUUGG5276CCAAAGATATGGCAATG4784979 CUGCUAACCUGAUGAGXCGAAACCAUUGC5277GCAATGGTAGTTAGCAG4894980 CAGCUGCUCUGAUGAGXCGAAACUACCAU5278ATGGTAGTTAGCAGCTG4924981 493 4982 CCAGCUGC CUGAUGAG X CGAA AACUACCA 5279 TGGTAGTT A GCAGCTGG 508 4983 GUCCUGCG CUGAUGAG X CGAA AUCUCGCC 5280 GGCGAGAT C CGCAGGAC 614 4984 GCGCGCCC CUGAUGAG X CGAA AGCCCGCC 5281 GGCGGGCT C GGGCGCGC 706 4985 CUGGCCCG CUGAUGAG X CGAA ACCGGGCG 5282 CGCCCGGT T CGGGCCAG 707 4986 UCUGGCCC CUGAUGAG X CGAA AACCGGGC 5283 GCCCGGTT C GGGCCAGA 729 4987 ACGCACUC CUGAUGAG X CGAA AUGUGCUG 5284 CAGCACAT C GAGTGCGT 755 4988 UGCCGCUC CUGAUGAG X CGAA ACUUGUCC 5285 GGACAAGT C GAGCGGCA 770 4989 AUUGGCCG CUGAUGAG X CGAA AGUGCUUG 5286 CAAGCACT A CGGCCAAT 779 4990 CGCAGGUG CUGAUGAG X CGAA AUUGGCCG 5287 CGGCCAAT T CACCTGCG 780 4991 UCGCAGGU CUGAUGAG X CGAA AAUUGGCC 5288 GGCCAATT C ACCTGCGA 802 4992 CUUGAAGA CUGAUGAG X CGAA ACUUUUGC 5289 GCAAAAGT T TCTTCAAG 803 4993 UCUUGAAG CUGAUGAG X CGAA AACUUUUG 5290 CAAAAGTT T CTTCAAGA 804 4994 CUCUUGAA CUGAUGAG X CGAA AAACUUUU 5291 AAAAGTTT C TTCAAGAG 806 4995 UCCUCUUG CUGAUGAG X CGAA AGAAACUU 5292 AAGTTTCT T CAAGAGGA Table V. Hammerheadbozymes to EAR3/COUP-TF-1 CUCCUCUUCUGAUGAGXCGAAAAGAAACU5293AGTTTCTTCAAGAGGAG8074996 UUCCUGCGCUGAUGAGXCGAAACGCUCCU5294AGGAGCGTCCGCAGGAA8194997 UGUAAGUUCUGAUGAGXCGAAAGUUCCUG5295CAGGAACTTAACTTACA8304998 GUGUAAGUCUGAUGAGXCGAAAAGUUCCU5296AGGAACTTAACTTACAC8314999 GCAUGUGUCUGAUGAGXCGAAAGUUAAGU5297ACTTAACTTACACATGC8355000 GGCAUGUGCUGAUGAGXCGAAAAGUUAAG5298CTTAACTTACACATGCC8365001 GUCGAUGGCUGAUGAGXCGAAACAGUUCC5299GGAACTGTCCCATCGAC8625002 UGCUGGUCCUGAUGAGXCGAAAUGGGACA5300TGTCCCATCGACCAGCA8675003 GGCGGCAGCUGAUGAGXCGAAAUUGGCAC5301GTGCCAATACTGCCGCC8965004 CACUUCUUCUGAUGAGXCGAAAGGCGGCA5302TGCCGCCTCAAGAAGTG9065005 918 5006 XCGAAAGGCACUU5303AAGTGCCTCAAAGTGGGCUGAUGAG CCUCGCUGCUGAUGAGXCGAAACCGCUUC5304GAAGCGGTTCAGCGAGG9455007 UCCUCGCUCUGAUGAGXCGAAAACCGCUU5305AAGCGGTTCAGCGAGGA9465008 CUGGCCUGCUGAUGAGXCGAAAUUGGGCU5307AGCCCAATCCAGGCCAG9795010 UGAGUGCGCUGAUGAGXCGAAACUGGCCU5308AGGCCAGTACGCACTCA9895011 996 5012 CCGUUGGU CUGAUGAG X CGAA AGUGCGUA 5309 TACGCACT C ACCAACGG 1014 5013 UGGCCGUU CUGAUGAG X CGAA AGGGGGUC 5310 GACCCCCT C AACGGCCA 1028 5014 CGGACAGG CUGAUGAG X CGAA AGCAGUGG 5311 CCACTGCT A CCTGTCCG 1034 5015 UGUAGCCG CUGAUGAG X CGAA ACAGGUAG 5312 CTACCTGT C CGGCTACA 1040 5016 GCCAGAUG CUGAUGAG X CGAA AGCOGGAC 5313 GTCCGGCT A CATCTCGC 1044 5017 AGCAGCGA CUGAUGAG X CGAA AUGUAGCC 5314 GGCTACAT C TCGCTGCT GCAGCAGCCUGAUGAGXCGAAAGAUGUAG5315CTACATCTCGCTGCTGC10465018 ACGUGGGGCUGAUGAGXCGAAAGGGCUCG5316CGAGCOCTACCCCACGT10705019 CGUAGCGCCUGAUGAGXCGAAACGUGGGG5317CCCCACGTCGCGCTACG10795020 1085 5021 GGCUGCCG CUGAUGAG X CGAA AGCGCGAC 5318 GTCGCGCT A CGGCAGCC 1116 5022 AUGCCCAU CUGAUGAG X CGAA AUGUUGUU 5319 AACAACAT T ATGGGCAT 1117 5023 GAUGCCCA CUGAUGAG X CGAA AAUGUUGU 5320 ACAACATT A TGGGCATC 1125 5024 AUGUUCUC CUGAUGAG X CGAA AUGCOCAU 5321 ATGGGCAT C GAGAACAT 1134 5025 AGCUCGCA CUGAUGAG X CGAA AUGUUCUC 5322 GAGAACAT C TGCGAGCT 1158 5026 GCGCUGAA CUGAUGAG X CGAA AGCAGGCG 5323 CGCCTGCT C TTCAGCGC 1160 5027 CGGCGCUG CUGAUGAG X CGAA AGAGCAGG 5324 CCTGCTCT T CAGCGCCG 1161 5028 ACGGCGCU CUGAUGAG X CGAA AAGAGCAG 5325 CTGCTCTT C AGCGCOGT 1170 5029 GCCCACUC CUGAUGAG X CGAA ACGGCGCU 5326 AGCGCCGT C GAGTGGGC 1188 5030 AAGAAGGG CUGAUGAG X CGAA AUGUUGCG 5327 CGCAACAT C COCTTCTT 1193 5031 CCGGGAAG CUGAUGAG X CGAA AGGGGALG 5328 CATCCCCT T CTTCCCGG 1194 5032 UCCGGGAA CUGAUGAG X CGAA AAGGGGAU 5329 ATCCCCTT C TTCCCGGA 1196 5033 GAUCCGGG CUGAUGAG X CGAA AGAAGGGG 5330 CCCCTTCT T CCCGGATC 1197 5034 AGAUCCGG CUGAUGAG X CGAA AAGAAGGG 5331 CCCTTCTT C CCGGATCT 1204 5035 GAUCUGCA CUGAUGAG X CGAA AUCCGGGA 5332 TCCCGGAT C TGCAGATC 1212 5036 UGGUCGGU CUGAUGAG X CGAA AUCUGCAG 5333 CTGCAGAT C ACCGACCA 1226 5037 GUAGCAGG CUGAUGAG X CGAA ACACCUGG 5534 CCAGGTGT C CCTGCTAC 1233 5038 GUGAGGCG CUGAUGAG X CGAA AGCAGGGA 5535 TCCCTGCT A CGCCTCAC 1239 5039 CUCCAGGU CUGAUGAG X CGAA AGGCGUAG 5336 CTACGCCT C ACCTGGAG 1256 5040 UGAGCACG CUGAUGAG X CGAA ACAGCUCG 5337 CGAGCTGT T CGTGCTCA 1257 5041 UUGAGCAC CUGAUGAG X CGAA AACAGCUC 5338 GAGCTGTT C GTGCTCAA 1263 5042 GCCGCGUU CUGAUGAG X CGAA AGCACGAA 5339 TTCGTGCT C AACGCGGC Table V. HamlTlerhe_ rdbozymes to EAR3/COUP-TF-1 1280 5043 GCGGCAUA CUGAUGAG X CGAA AGCACUGG 5340 CCAGTGCT C TATGCCGC CAGCGGCACUGAUGAGXCGAAAGAGCACU5341AGTGCTCTATGCCGCTG12825044 CGGCCAGCCUGAUGAGXCGAAACGGCGCC5342GGCGCCGTTGCTGGCCG13045045 ACAUGGGCCUGAUGAGXCGAAAGGCAUGC5343GCATGCCTCGCCCATGT13315046 GGUCGGCACUGAUGAGXCGAAACAUGGGC5344GCCCATGTCTGCCGACC13405047 AAGGCCACCUGAUGAGXCGAAACGCGGUC5345GACCGCGTCGTGGCCTT13535048 GGUCCAUGCUGAUGAGXCGAAAGGCCACG5346CGTGGCCTTCATGGACC13615049 UGGUCCAUCUGAUGAGXCGAAAAGGCCAC5347GTGGCCTTCATGGACCA13625050 1374 5051 AAGAUGCG CUGAUGAG X CGAA AUGUGGUC 5348 GACCACAT C CGCATCTT UCCUGGAACUGAUGAGXCGAAAUGCGGAU5349ATCOGCATCTTOCAGGA13805052 1382 CUGAUGAGXCGAAAGAUGCGG5350CCGCATCTTCCAGGAGCGCUCCUGG UGCUCCUGCUGAUGAGXCGAAAAGAUGCG5351CGCATCTTCCAGGAGCA13835054 AGCGCCUUCUGAUGAGXCGAAAGCUUCUC5352GAGAAGCTCAAGGCGCT14045055 UCGACGUGCUGAUGAGXCGAAAGCGCCUU5353AAGGCGCTACACGTCGA14135056 1419 5057 GCUGAGUC CUGAUGAG X CGAA ACGUGUAG 5354 CTACACGT C GACTCAGC 1424 5058 ACUCGGCU CUGAUGAG X CGAA AGUCGACG 5355 CGTCGACT C AGCCGAGT 1433 5059 GGCAGCUG CUGAUGAG X CGAA ACUCGGCU 5356 AGCCGAGT A CAGCTGCC AUGGCUUUCUGAUGAGXCGAAAGGCAGCU5357AGCTGCCTCAAAGCCAT14435060 1452 5061 AACAGCAC CUGAUGAG X CGAA AUGGCUUU 5358 AAAGCCAT C GTGCTGTT 1460 5062 XCGAAACAGCACG5359CGTGCTGTTCACGTCAGCUGAUGAG 1461 5063 UCUGACGU CUGAUGAG X CGAA AACAGCAC 5360 GTGCTGTT C ACGTCAGA 1466 5064 AGGCGUCU CUGAUGAG X CGAA ACGUGAAC 5361 GTTCACGT C AGACGOCT 1484 5065 CCGCAUCC CUGAUGAG X CGAA ACAGGCCA 5362 TGGCCTGT C GGATGCGG 1500 5066 AGGCUCUC CUGAUGAG X CGAA AUGUGGGC 5363 GCCCACAT C GAGAGCCT 1520 5067 CGCACUGC CUGAUGAG X CGAA ACUUCUCC 5364 GGAGAAGT C GCAGTGCG 1541 5068 UCCUCACG CUGAUGAG X CGAA ACUCCUCC 5365 GGAGGAGT A CGTGAGGA GGUUGGGGCUGAUGAGXCGAAACUGGCUC5366GAGCCAGTACCCCAACC15565069 UUUGCCAACUGAUGAGXCGAAACGGCUGG5367CCAGCCGTTTTGGCAAA15765070 GUUUGCCACUGAUGAGXCGAAAACGGCUG5368CAGCCGTTTTGGCAAAC15775071 AGUUUGCCCUGAUGAGXCGAAAAACGGCU5369AGCCGTTTTGGCAAACT15785072 1604 5073 XCGAAAGGGCAGU5370ACTGCCCTCGCTGCGCACUGAUGAG CGGAGGAGCUGAUGAGXCGAAACACGGUG5371CACCGTGTCCTCCTCCG16195074 1622 5075 UGACGGAG CUGAUGAG X CGAA AGGACACG 5372 CGTGTCCT C CTCCGTCA 1625 5076 CGAUGACG CUGAUGAG X CGAA AGGAGGAC 5373 TGCCTCCT C CGTCATCG 1629 5077 UGCUCGAU CUGAUGAG X CGAA ACGGAGGA 5374 TCCTCCGT C ATCGAGCA 1632 5078 AGCUGCUC CUGAUGAG X CGAA AUGACGGA 5375 TCCGTCAT C GAGCAGCT 1641 5079 ACGAAGAA CUGAUGAG X CGAA AGCUGCUC 5376 GAGCAGCT C TTCTTCGT 1643 5080 GGACGAAG CUGAUGAG X CGAA AGAGCUGC 5377 GCAGCTCT T CTTCGTCC 1644 5081 OGGACGAA CUGAUGAG X CGAA AAGAGCUG 5378 CAGCTCTT C TTCGTCCG 1646 5082 AACGGACG CUGAUGAG X CGAA AGAAGAGC 5379 GCTCTTCT T CGTCCGTT 1647 5083 AAACGGAC CUGAUGAG X CGAA AAGAAGAG 5380 CTCTTCTT C GTCCGTTT 1650 5084 ACCAAACG CUGAUGAG X CGAA ACGAAGAA 5381 TTCTTCGT C CGTTTGGT 1654 5085 ACCUACCA CUGAUGAG X CGAA ACGGACGA 5382 TCGTCCGT T TGGTAGGT 1655 5086 UACCUACC CUGAUGAG X CGAA AACGGACG 5383 CGTCCGTT T GGTAGGTA 1659 5087 GUUUUACC CUGAUGAG X CGAA ACCAAACG 5384 CGTTTGGT A GGTAAAAC 1663 5088 GGGGGUUU CUGAUGAG X CGAA ACCUACCA 5385 TGGTAGGT A AAACCCCC 1674 5089 AGAGUUUC CUGAUGAG X CGAA AUGGGGGU 5386 ACCCCCAT C GAAACTCT Table V. Hammerhea@@@bozymes to EAR3/COUP-TF-1 GCGGAUGACUGAUGAGXCGAAAGUUUCGA5387TCGAAACTCTCATCCGC16815090 AUAUCGCGCUGAUGAGXCGAAAUGAGAGU5389ACTCTCATCCGCGATAT16865092 CAGUAACACUGAUGAGXCGAAAUCGCGGA5390TCCGCGATATGTTACTG16935093 CAGACAGUCUGAUGAGXCGAAACAUAUCG5391OGATATGTTACTGTCTG16975094 CCAGACAGCUGAUGAGXCGAAAACAUAUC5392GATATGTTACTGTCTGG16985095 UGCUCCCACUGAUGAGXCGAAACAGUAAC5393GTTACTGTCTGGGAGCA17035096 GCCAGUUGCUGAUGAGXCGAAAGCUGCUC5394GAGCAGCTTCAACTGGC17155097 GGCCAGUUCUGAUGAGXCGAAAAGCUGCU5395AGCAGCTTCAACTGGCC17165098 GGACAUGUCUGAUGAGXCGAAAGGCCAGU5396ACTGGCCTTACATGTCC17265099 1727 5100 UGGACAUG CUGAUGAG X CGAA AAGGCCAG 5397 CTGGCCTT A CATGTCCA 1733 5101 ACUGGAUG CUGAUGAG X CGAA ACAUGUAA 5398 TTACATGT C CATCCAGT GAGCACUGCUGAUGAGXCGAAAUGGACAU5399ATGTCCATCCAGTGCTC17375102 AGGUCUAGCUGAUGAGXCGAAAGCACUGG5400CCAGTGCTCCTAGACCT17455103 CCAAGGUCCUGAUGAGXCGAAAGGAGCAC5401GTGCTCCTAGACCTTGG17485104 AAGCGCCCCUGAUGAGXCGAAAGGUCUAG5402CTAGACCTTGGGCGCTT17545105 GAGGUGGGCUGAUGAGXCGAAAGCGCCCA5403TGGGCGCTTCCCACCTG17625106 GCAGGUGGCUGAUGAGXCGAAAAGCGCCC5404GGGCGCTTCCCACCTGC17635107 UCUAGGGGCUGAUGAGXCGAAACGGGGCA5405TGCCCCGTCCCCCTAGA17775108 UGAGUCUCCUGAUGAGXCGAAAGGGGGAC5406GTCCCCCTAGAGACTGA17835109 GGUCCUCUCUGAUGAGXCGAAAGUCUCUA5407TAGAGACTCAGAGGACC17905110 1816 5111 CGGCUUUG CUGAUGAG X CGAA AGUCCUUG 5408 CAAGGACT C CAAAGCCG 1910 5112 UCGGAUUG CUGAUGAG X CGAA AUUUCUGC 5409 GCAGAAAT A CAATCCGA 1915 5113 GUAGCUCG CUGAUGAG X CGAA AUUGUAUU 5410 AATACAAT C CGAGCTAC 1922 5114 AUGCUUUG CUGAUGAG X CGAA AGCUCGGA 5411 TCCGAGCT A CAAAGCAT 1945 5115 UCCUAAAA CUGAUGAG X CGAA AGUCUCUU 5412 AAGAGACT C TTTTAGGA 1947 5116 GAUCCUAA CUGAUGAG X CGAA AGAGUCUC 5413 GAGACTCT T TTAGGATC 1948 5117 UGAUCCUA CUGAUGAG X CGAA AAGAGUCU 5414 AGACTCTT T TAGGATCA 1949 5118 CUGAUCCU CUGAUGAG X CGAA AAAGAGUC 5415 GACTCTTT T AGGATCAG 1950 5119 UCUGAUCC CUGAUGAG X CGAA AAAAGAGU 5416 ACTCTTTT A GGATCAGA 1955 5120 ACAGAUCU CUGAUGAG X CGAA AUCCUAAA 5417 TTTAGGAT C AGATCTGT 1960 5121 UGCUCACA CUGAUGAG X CGAA AUCUGAUC 5418 GATCAGAT C TGTGAGCA 1972 5122 UCCUCGCC CUGAUGAG X CGAA ACGUGCUC 5419 GAGCACGT T GGCGAGGA 2009 5123 ACAGACAC CUGAUGAG X CGAA AGGUUCUU 5420 AAGAACCT T GTGTCTGT 2014 5124 ACCAGACA CUGAUGAG X CGAA ACACAAGG 5421 CCTTGTGT C TGTCTGGT 2018 5125 UUUCACCA CUGAUGAG X GGAA ACAGACAC 5422 GTGTCTGT C TGGTGAAA 2042 5126 UCUCUUCC CUGAUGAG X CGAA AUUUGUUU 5423 AAACAAAT T GGAAGAGA 2064 5127 UUUAUUAA CUGAUGAG X CGAA AUUCUCAU 5424 ATGAGAAT T TTAATAAA 2065 5128 UUUUAUUA CUGAUGAG X CGAA AAUUCUCA 5425 TGAGAATT T TAATAAAA 2066 5129 GUUUUAUU CUGAUGAG X CGAA AAAUUCUC 5426 GAGAATTT T AATAAAAC 2067 5130 UGUUUUAU CUGAUGAG X CGAA AAAAUUUU 5427 AGAATTTT A ATAAAACA 2070 5131 UUCUGUUU CUGAUGAG X CGAA AUUAAAAU 5428 ATTTTAAT A AAACAGAA 2086 5132 AGGUCCAU CUGAUGAG X CGAA AGUUUCCU 5429 AGGAAACT A ATGGACCT 2095 5133 AAUCCUGG CUGAUGAG X CGAA AGGUCCAU 5430 ATGGACCT T CCAGGATT 2096 5134 AAAUCCUG CUGAUGAG X CGAA AAGGUCCA 5431 TGGACCTT C CAGGATTT 2103 5135 CCACAAUA CUGAUGAG X CGAA AUCCUGGA 5432 TCCAGGAT T TATTGTGG 2104 5136 UCCACAAU CUGAUGAG X CGAA AAUCCUGG 5433 CCAGGATT T ATTGTGGA Table V. HammerheX., bozymes to EAR3/COUP-TF-1 2105 CUGAUGAGXCGAAAAAUCCUG5434CAGGATTTATTGTGGACGUCCACAA CCGUCCACCUGAUGAGXCGAAAUAAAUCC5434GGATTTATTGTGGACGG21075138 ACAGAAUACUGAUGAGXCGAAAUCCACAU5436ATGTGGATATATTCTGT21245139 GUACAGAACUGAUGAGXCGAAAUAUCCAC5437GTGGATATATTCTGTAC21265140 CUGUACAGCUGAUGAGXCGAAAUAUAUCC5438GGATATATTCTGTACAG21285141 CCUGUACACUGAUGAGXCGAAAAUAUAUC5439GATATATTCTGTACAGG21295142 UGUUCCUGCUGAUGAGXCGAAACAGAAUA5440TATTCTGTACAGGAACA21335143 CACUUCCACUGAUGAGXCGAAAUGUGUUG5441CAACACATATGGAAGTG21485144 UUUCUACACUGAUGAGXCGAAAGGCUUCA5442TGAAGCCTATGTAGAAA21685145 UGUGUUUCCUGAUGAGXCGAAACAUAGGC5443GCCTATGTAGAAACACA21725146 UGAAUAACCUGAUGAGXCGAAAUGUUCAG5444CTGAACATTGTTATTCA21955147 AAAUGAAUCUGAUGAGXCGAAACAAUGUU5445AACATTGTTATTCATTT21985148 AAAAUGAACUGAUGAGXCGAAAACAAUGU5446ACATTGTTATTCATTTT21995149 ACAAAAUGCUGAUGAGXCGAAAUAACAAU5447ATTGTTATTCATTTTGT22015150 2202 5151 UACAAAAU CUGAUGAG X CGAA AAUAACAA 5448 TTGTTATT C ATTTTGTA UUUUACAACUGAUGAGXCGAAAUGAAUAA5449TTATTCATTTTGTAAAA22055152 AUUUUACACUGAUGAGXCGAAAAUGAAUA5450TATTCATTTTGTAAAAT22065153 UAUUUUACCUGAUGAGXCGAAAAAUGAAU5451ATTCATTTTGTAAAATA22075154 2210 5155 UAGUAUUU CUGAUGAG X CGAA ACAAAAUG 5452 CATTTTGT A AAATACTA 2215 5156 AAGACUAG CUGAUGAG X CGAA AUUUUACA 5453 TGTAAAAT A CTAGTCTT 2218 5157 AUAAAGAC CUGAUGAG X CGAA AGUAUUUU 5454 AAAATACT A GTCTTTAT 2221 5158 AAAAUAAA CUGAUGAG X CGAA ACUAGUAU 5455 ATACTAGT C TTTATTTT 2223 5159 UGAAAAUA CUGAUGAG X CGAA AGACUAGU 5456 ACTAGTCT T TATTTTCA 2224 5160 AUGAAAAU CUGAUGAG X CGAA AAGACUAG 5457 CTAGTCTT T ATTTTCAT 2225 5161 AAUGAAAA CUGAUGAG X CGAA AAAGACUA 5458 TAGTCTTT A TTTTCATT 2227 5162 AAAAUGAA CUGAUGAG X CGAA AUAAAGAC 5459 GTCTTTAT T TTCATTTT 2228 5163 AAAAAUGA CUGAUGAG X CGAA AAUAAAGA 5460 TCTTTATT T TCATTTTT 2229 5164 AAAAAAUG CUGAUGAG X CGAA AAAUAAAG 5461 CTTTATTT T CATTTTTT 2230 5165 CAAAAAAU CUGAUGAG X CGAA AAAAUAAA 5462 TTTATTTT C ATTTTTTG 2233 5166 UUACAAAA CUGAUGAG X CGAA AUGAAAAU 5463 ATTTTCAT T TTTTGTAA 2234 5167 UUUACAAA CUGAUGAG X CGAA AAUGAAAA 5464 TTTTCATT T TTTGTAAA 2235 5168 UUUUACAA CUGAUGAG X CGAA AAAUGAAA 5465 TTTCATTT T TTGTAAAA 2236 5169 AUUUUACA CUGAUGAG X CGAA AAAAUGAA 5466 TTCATTTT T TGTAAAAT 2237 5170 AAUUUUAC CUGAUGAG X CGAA AAAAAUGA 5467 TCATTTTT T GTAAAATT 2240 5171 UUAAAUUU CUGAUGAG X CGAA ACAAAAAA 5468 TTTTTTGT A AAATTTAA 2245 5172 GAUGUUUA CUGAUGAG X CGAA AUUUUACA 5469 TGTAAAAT T TAAACATC 2246 5173 CGAUGUUU CUGAUGAG X CGAA AAUUUUAC 5470 GTAAAATT T AAACATCG 2247 5174 ACGAUGUU CUGAUGAG X CGAA AAAUUUUA 5471 TAAAATTT A AACATCGT 2253 5175 GCGCAUAC CUGAUGAG X CGAA AUGUUUAA 5472 TTAAACAT C GTATGCGC 2256 5176 UAUGCGCA CUGAUGAG X CGAA ACGAUGUU 5473 AACATCGT A TGCGCATA 2264 5177 UUUUUCUU CUGAUGAG X CGAA AUGCGCAU 5474 ATGCGCAT A AAGAAAAA 2285 5178 UUUCCCCU CUGAUGAG X CGAA AUUCUUGU 5475 ACAAGAAT T AGGGGAAA 2286 5179 UUUUCCCC CUGAUGAG X CGAA AAUUCUUG 5476 CAAGAATT A GGGGAAAA 2296 5180 GAAAAUGU CUGAUGAG X CGAA AUUUUCCC 5477 GGGAAAAT A ACATTTTC 2301 5181 AUUUGGAA CUGAUGAG X CGAA AUGUUAUU 5478 AATAACAT T TTCCAAAT 2302 5182 UAUUUGGA CUGAUGAG X CGAA AAUGUUAU 5479 ATAACATT T TCCAAATA 2303 5183 UUAUUUGG CUGAUGAG X CGAA AAAUGUUA 5480 TAACATTT T CCAAATAA Table V. Hammerhe... bozymes to EAR3/COUP-TF-1 AUUAUUUGCUGAUGAGXCGAAAAAAUGUU5481AACATTTTCCAAATAAT23045184 2310 5185 XCGAAAUUUGGAA5482TTCCAAATAATTATAAACUGAUGAG UUUUUUAUCUGAUGAGXCGAAAUUAUUUG5483CAAATAATTATAAAAAA23135186 2314 5187 AUUUUUUA CUGAUGAG X CGAA AAUUAUUU 5484 AAATAATT A TAAAAAAT CAAUUUUUCUGAUGAGXCGAAAUAAUUAU5485ATAATTATAAAAAATTG23165188 CACAGGACCUGAUGAGXCGAAAUUUUUUA5486TAAAAAATTGTCCTGTG23235189 AGACACAGCUGAUGAGXCGAAACAAUUUU5487AAAATTGTCCTGTGTCT23265190 GAUACAUACUGAUGAGXCGAAACACAGGA5488TCCTGTGTCTATGTATC23335191 UAGAUACACUGAUGAGXCGAAAGACACAG5489CTGTGTCTATGTATCTA23355192 GAUAUAGACUGAUGAGXCGAAACAUAGAC5490GTCTATGTATCTATATC23395193 CAGAUAUACUGAUGAGXCGAAAUACAUAG5491CTATGTATCTATATCTG23415194 2343 5195 AACAGAUA CUGAUGAG X CGAA AGAUACAU 5492 ATGTATCT A TATCTGTT AAAACAGACUGAUGAGXCGAAAUAGAUAC5493GTATCTATATCTGTTTT23455196 2347 5197 ACAAAACA CUGAUGAG X CGAA AUAUAGAU 5494 ATCTATAT C TGTTTTGT AAAUACAACUGAUGAGXCGAAACAGAUAU5495ATATCTGTTTTGTATTT23515198 AAAAUACACUGAUGAGXCGAAAACAGAUA5496TATCTGTTTTGTATTTT23525199 AAAAAUACCUGAUGAGXCGAAAAACAGAU5497ATCTGTTTTGTATTTTT23535200 GAAAAAAACUGAUGAGXCGAAACAAAACA5498TGTTTTGTATTTTTTTC23565201 GAGAAAAACUGAUGAGXCGAAAUACAAAA5499TTTTGTATTTTTTTCTG23585202 CCAGAAAACUGAUGAGXCGAAAAUACAAA5500TTTGTATTTTTTTCTGG23595203 ACCAGAAACUGAUGAGXCGAAAAAUACAA5501TTGTATTTTTTTCTGGT23605204 2361 5205 AACCAGAA CUGAUGAG X CGAA AAAAUACA 5502 TGTATTTT T TTCTGGTT 2362 5206 GAACCAGA CUGAUGAG X CGAA AAAAAUAC 5503 GTATTTTT T TCTGGTTC 2363 5207 GGAACCAG CUGAUGAG X CGAA AAAAAAUA 5504 TATTTTTT T CTGGTTCC 2364 5208 UGGAACCA CUGAUGAG X CGAA AAAAAAAU 5505 ATTTTTTT C TGGTTCCA 2369 5209 UGGUUUGG CUGAUGAG X CGAA ACCAGAAA 5506 TTTCTGGT T CCAAACCA 2370 5210 CUGGUUUG CUGAUGAG X CGAA AACCAGAA 5507 TTCTGGTT C CAAACCAG 2381 5211 UCACAGGA CUGAUGAG X CGAA AUCUGGUU 5508 AACCAGAT T TCCTGTGA 2382 5212 AUCACAGG CUGAUGAG X CGAA AAUCUGGU 5509 ACCAGATT T CCTGTGAT 2383 5213 AAUCACAG CUGAUGAG X CGAA AAAUCUGG 5510 CCAGATTT C CTGTGATT 2391 5214 UAGUAUAG CUGAUGAG X CGAA AUCACAGG 5511 OCTGTGAT T CTATACTA 2392 5215 UUAGUAUA CUGAUGAG X CGAA AAUCACAG 5512 CTGTGATT C TATACTAA 2394 5216 UAUUAGUA CUGAUGAG X OGAA AGAAUCAC 5513 GTGATTCT A TACTAATA 2396 5217 AUUAUUAG CUGAUGAG X CGAA AUAGAAUC 5514 GATTCTAT A CTAATAAT 2399 5218 AAAAUUAU CUGAUGAG X CGAA AGUAUAGA 5515 TCTATACT A ATAATTTT 2402 5219 UCAAAAAU CUGAUGAG X CGAA AUUAGUAU 5516 ATACTAAT A ATTTTTGA 2405 5220 AUAUCAAA CUGAUGAG X CGAA AUUAUUAG 5517 CTAATAAT T TTTGATAT 2406 5221 UAUAUCAA CUGAUGAG X CGAA AAUUAUUA 5518 TAATAATT T TTGATATA 2407 5222 UUAUAUCA CUGAUGAG X CGAA AAAUUAUU 5519 AATAATTT T TGATATAA 2408 5223 GUUAUAUC CUGAUGAG X CGAA AAAAUUAU 5520 ATAATTTT T GATATAAC 2412 5224 AAGGGUUA CUGAUGAG X CGAA AUCAAAAA 5521 TTTTTGAT A TAACCCTT 2414 5225 CAAAGGGU CUGAUGAG X CGAA AUAUCAAA 5522 TTTGATAT A ACCCTTTG 2420 5226 AAGAAGCA CUGAUGAG X CGAA AGGGUUAU 5523 ATAACCCT T TGCTTCTT 2421 5227 UAAGAAGC CUGAUGAG X CGAA AAGGGUUA 5524 TAACCCTT T GCTTCTTA 2425 5228 AUUAUAAG CUGAUGAG X CGAA AGCAAAGG 5525 CCTTTGCT T CTTATAAT 2426 5229 CAUUAUAA CUGAUGAG X CGAA AAGCAAAG 5526 CTTTGCTT C TTATAATG 2428 5230 CUCAUUAU CUGAUGAG X CGAA AGAAGCAA 5527 TTGCTTCT T ATAATGAG Table V. Hammerhe. bozymes to EAR3/COUP-TF-1 ACUCAUUACUGAUGAGXCGAAAAGAAGCA5528TGCTTCTTATAATGAGT24295231 GCACUCAUCUGAUGAGXCGAAAUAAGAAG5529CTTCTTATAATGAGTGC24315232 ACAACAUACUGAUGAGXCGAAAUCGCACU5530AGTGCGATATATGTTGT24435233 CGACAACACUGAUGAGXCGAAAUAUCGCA5531TGCGATATATGTTGTCG24455234 GCCUCGACCUGAUGAGXCGAAACAUAUAU5532ATATATGTTGTCGAGGC24495235 2461 5237 UCUUGAAG CUGAUGAG X CGAA ACAGCCUC 5534 GAGGCTGT T CTTCAAGA UUCUUGAACUGAUGAGXCGAAAACAGCCU5535AGGCTGTTCTTCAAGAA24625238 AAUUCUUGCUGAUGAGXCGAAAGAACAGC5536GCTGTTCTTCAAGAATT24645239 UAAUUCUUCUGAUGAGXCGAAAAGAACAG5537CTGTTCTTCAAGAATTA24655240 2472 5241 UCAAUUUU CUGAUGAG X CGAA AUUCUUGA 5538 TCAAGAAT T AAAATTGA 2473 5242 UUCAAUUU CUGAUGAG X CGAA AAUUCUUG 5539 CAAGAATT A AAATTGAA UUCACUUCCUGAUGAGXCGAAAUUUUAAU5540ATTAAAATTGAAGTGAA24785243 UUUGUUUACUGAUGAGXCGAAAUUUUCAC5541GTGAAAATTTAAACAAA24905244 UUUUGUUUCUGAUGAGXCGAAAAUUUUCA5542TGAAAATTTAAACAAAA24915245 UUUUUGUUCUGAUGAGXCGAAAAAUUUUC5543GAAAATTTAAACAAAAA24925246 AAUUCUUUCUGAUGAGXCGAAAUUUUUGU5544ACAAAAATAAAAGAATT25025247 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.

Table VI. Hammerht ibozymes to IRF-2 Pos Seq. RZ Seq. Substrate I.D. No. I.D. No. 13 5545 XCGAAAGCCCGUC5967GACGGGCUUUCAUUUCCCUGAUGAG 14 CUGAUGAGXCGAAAAGCCCGU5968ACGGGCUUUCAUUUCCAUGGAAAUG 15 5547 XCGAAAAAGCCCG5969CGGGCUUUCAUUUCCAUCUGAUGAG GAAAUGGACUGAUGAGXCGAAAUGAAAGC5970GCUUUCAUUUCCAUUUC185548 UGAAAUGGCUGAUGAGXCGAAAAUGAAAG5971CUUUCAUUUCCAUUUCA195549 GUGAAAUGCUGAUGAGXCGAAAAAUGAAA5972UUUCAUUUCCAUUUCAC205550 GUGUGUGACUGAUGAGXCGAAAUGGAAAU5973AUUUCCAUUUCACACAC245551 25 5552 XCGAAAAUGGAAA5974UUUCCAUUUCACACACCCUGAUGAG 26 5553 XCGAAAAAUGGAA5975UUCCAUUUCACACACCCCUGAUGAG 36 CUGAUGAGXCGAAAGGGUGUG5976CACACCCUAGCAACACUAGUGUUGC CAAGGUAUCUGAUGAGXCGAAAGUGUUGC5977GCAACACUUAUACCUUG455555 46 5556 GCAAGGUA CUGAUGAG X CGAA AAGUGUUG 5978 CAACACUU A UACCUUGC 48 5557 CCGCAAGG CUGAUGAG X CGAA AUAAGUGU 5979 ACACUUAU A CCUUGOGG 52 5558 AAUUCCGC CUGAUGAG X CGAA AGGUAUAA 5980 UUAUACCU U GCGGAAUU ACCAAUACCUGAUGAGXCGAAAUUCCGCA5981UGCGGAAUUGUAUUGGU605559 63 5560 GCUACCAA CUGAUGAG X CGAA ACAAUUCC 5982 GGAAUUGU A UUGGUAGC 65 5561 ACGCUACC CUGAUGAG X CGAA AUACAAUU 5983 AAUUGUAU U GGUAGCGU 69 5562 UUUCACGC CUGAUGAG X CGAA ACCAAUAC 5984 GUAUUGGU A GCGUGAAA 146 5563 UUGGAGUU CUGAUGAG X CGAA AUCUGCUC 5985 GAGCAGAU A AACUCCAA 151 5564 XCGAAAGUUUAUC5986GAUAAACUCCAACACGACUGAUGAG 161 5565 AGCCCCGG CUGAUGAG X CGAA AUCGUGUU 5987 AACACGAU C CCGGGGCU 170 5566 AGCCACUU CUGAUGAG X CGAA AGCCCCGG 5988 CCGGGGCU C AAGUGGCU 179 5567 UCCUUGUU CUGAUGAG X CGAA AGCCACUU 5989 AAGUGGCU U AACAAGGA 180 5568 UUCCUUGU CUGAUGAG X CGAA AAGCCACU 5990 AGUGGCUU A ACAAGGAA 197 5569 AUCUGAAA CUGAUGAG X CGAA AUCUUCUU 5991 AAGAAGAU U UUUCAGAU GAUCUGAACUGAUGAGXCGAAAAUCUUCU5992AGAAGAUUUUUCAGAUC1985570 199 5571 GGAUCUGA CUGAUGAG X CGAA AAAUCUUC 5993 GAAGAUUU U UCAGAUCC 200 5572 GGGAUCUG CUGAUGAG X CGAA AAAAUCUU 5994 AAGAUUUU U CAGAUCCC 201 5573 GGGGAUCU CUGAUGAG X CGAA AAAAAUCU 5995 AGAUUUUU C AGAUCCCC AUCCAGGGCUGAUGAGXCGAAAUCUGAAA5996UUUCAGAUCCCCUGGAU2065574 225 CUGAUGAGXCGAAACCCGCAU5997AUGCGGCUAGACAUGGGCCCAUGUC UUUCUAAACUGAUGAGXCGAAAGUGGUGC5998GCACCACUCUUUAGAAA2605576 GGUUUCUACUGAUGAGXCGAAAGAGUGGU5999ACCACUCUUUAGAAACC2625577 CGGUUUCUCUGAUGAGXCGAAAAGAGUGG6000CCACUCUUUAGAAACCG2635578 264 5579 XCGAAAAAGAGUG6001CACUCUUUAGAAACCGGCUGAUGAG 278 5580 XCGAAAUUGCCCG6002CGGGCAAUCCAUACAGGCUGAUGAG 282 5581 XCGAAAUGGAUUG6003CAAUCCAUACAGGAAAGCUGAUGAG UCCUGGUUCUGAUGAGXCGAAAUGCUUUC6004GAAAGCAUCAACCAGGA2945582 305 5583 GGUUUAUC CUGAUGAG X CGAA ACUCCUGG 6005 CCAGGAGU A GAUAAACC 309 CUGAUGAGXCGAAAUCUACUC6006GAGUAGAUAAACCUGAUAUCAGGUU UGUUUUGGCUGAUGAGXCGAAAUCAGGUU6007AACCUGAUCCCAAAACA3185585 GCAUCUGACUGAUGAGXCGAAAUUCGCCU6008AGGCGAAUUUCAGAUGC3395586 340 CUGAUGAGXCGAAAAUUCGCC6009GGCGAAUUUCAGAUGCGCGCAUCUG GCGCAUCUCUGAUGAGXCGAAAAAUUCGC6010GCGAAUUUCAGAUGCGC3415588 357 5589 AGGCAAGG CUGAUGAG X CGAA AUUCAUGG 6011 CCAUGAAU U CCUUGCCU Table VI. Hammerheau Ribozymes to IRF-2 358 5590 CAGGCAAG CUGAUGAG X CGAA AAUUCAUG 6012 CAUGAAUU C CUUGCCUG UAUCAGGCCUGAUGAGXCGAAAGGAAUUC6013GAAUUCCUUGCCUGAUA3615591 UUCUUCAACUGAUGAGXCGAAAUCAGGCA6014UGCCUGAUAUUGAAGAA3695592 ACUUCUUCCUGAUGAGXCGAAAUAUCAGG6015CCUGAUAUUGAAGAAGU3715593 UUAUCCUUCUGAUGAGXCGAAACUUCUUC6016GAAGAAGUCAAGGAUAA3805594 UAUGCUUUCUGAUGAGXCGAAAUCCUUGA6017UCAAGGAUAAAAGCAUA3875595 395 CUGAUGAGXCGAAAUGCUUUU6018AAAAGCAUAAAGAAAGGCCUUUCUU 408 CUGAUGAGXCGAAAUUUCCUU6019AAGGAAAUAAUGCCUUCGAAGGCAU AGACCCUGCUGAUGAGXCGAAAGGCAUUA6020UAAUGCCUUCAGGGUCU4155598 UAGACCCUCUGAUGAGXCGAAAAGGCAUU6021AAUGCCUUCAGGGUCUA4165599 AUUCGGUACUGAUGAGXCGAAACCCUGAA6022UUCAGGGUCUACCGAAU4225600 424 5601 XCGAAAGACCCUG6023CAGGGUCUACCGAAUGCCUGAUGAG CGUUCUGACUGAUGAGXCGAAAGGGGCAG6024CUGCCCCUAUCAGAACG4405602 GCCGUUCUCUGAUGAGXCGAAAUAGGGGC6025GCCCCUAUCAGAACGGC4425603 453 5604 UUUCUUAG CUGAUGAG X CGAA AGGCCGUU 6026 AACGGCCU U CUAAGAAA 454 5605 CUUUCUUA CUGAUGAG X CGAA AAGGCCGU 6027 ACGGCCUU C UAAGAAAG 456 5606UCCUUUCU CUGAUGAG X CGAA AGAAGGCC 6028 GGCCUUCU A AGAAAGGA 497 5607AUGUGCUU CUGAUGAG X CGAA ACUUUGUC 6029 GACAAAGU U AAGCACAU 498 5608 GAUGUGCU CUGAUGAG X CGAA AACUUUGU 6030 ACAAAGUU A AGCACAUC 506 5609 UCUUGCUU CUGAUGAG X CGAA AUGUGCUU 6031 AAGCACAU C AAGCAAGA 521 5610GAUGACUC CUGAUGAG X CGAA ACUGGUUC 6032 GAACCAGU U GAGUCAUC 526 5611 CCAGAGAU CUGAUGAG X CGAA ACUCAACU 6033 AGUUGAGU C AUCUCUGG GCCCCAGACUGAUGAGXCGAAAUGACUCA6034UGAGUCAUCUCUGGGGC5295612 529 5612 GCCCCAGA CUGAUGAG X CGAA AUGACUCA 6034 UGAGUCAU C UC 531 5613 XCGAAAGAUGACU6035AGUCAUCUCUGGGGCUUCUGAUGAG CCAUUACUCUGAUGAGXCGAAAGCCCCAG6036CUGGGGCUUAGUAAUGG5395614 540 5615 UCCAUUAC CUGAUGAG X CGAA AAGCCCCA 6037 UGGGGCUU A GUAAUGGA 543 5616 UACUCCAU CUGAUGAG X CGAA ACUAAGCC 6038 GGCUUAGU A AUGGAGUA 551 5617 AGAUCACU CUGAUGAG X CGAA ACUCCAUU 6039 AAUGGAGU A AGUGAUCU 558 5618 AGGAGAAA CUGAUGAG X CGAA AUCACUUA 6040 UAAGUGAU C UUUCUCCU 560 5619 UCAGGAGA CUGAUGAG X CGAA AGAUCACU 6041 AGUGAUCU U LlcLiccmk 561 5620 CUCAGGAG CUGAUGAG X CGAA AAGAUCAC 6042 GUGAUCUU U CUCCUGAG 562 5621 ACUCAGGA CUGAUGAG X CGAA AAAGAUCA 6043 UGAUCUUU C UCCUGAGU 564 5622 AUACUCAG CUGAUGAG X CGAA AGAAAGAU 6044 AUCUUUCU C CUGAGUAU 571 5623 GGACCGCA UCGAUGAG X CGAA ACUCAGGA 6045 UCCUGAGU A UGCGGUCC 578 5624 GAAGUCAG CUGAUGAG X CGAA ACCGCAUA 6046 UAUGCGGU C CUGACUUC 585 5625 UAUAGUUG CUGAUGAG X CGAA AGUCAGGA 6047 UCCUGACU U CAACUAUA 586 5626 UUAUAGUU CUGAUGAG X CGAA AAGUCAGG 6048 CCUGACUU C AACLWJAA 591 5627 AUUUUUUA CUGAUGAG X CGAA AGUUGAAG 6049 CUUCAACU A UAAAAAAU 593 5628 UCAUUUUU CUGAUGAG X CGAA AUAGUUGA 6050 UCAACUAU A AAAAAUGA 609 5629 CACCGUAC CUGAUGAG X CGAA AUCCACUU 6051 AAGUGGAU A GUACGGUG 609 5629 CACCGUAC CUGAUGAG X CGAA AUCCACUU 6051 AAGUGW A GLPD= 612 5630 GUUCACCG CUGAUGAG X CGAA ACUAUCCA 6052 UGGAUAGU A CGGUGAAC 623 5631 ACAACUAU CUGAUGAG X CGAA AUGUUCAC 6053 GUGAACAU C AUAGUUGU 626 5632 CCUACAAC CUGAUGAG X CGAA AUGAUGUU 6054 AACAUCAU A GUUGUAGG 629 5633 UGUCCUAC CUGAUGAG X CGAA ACUAUGAU 6055 AUCAUAGU U R 632 5634 GACUGUCC CUGAUGAG X CGAA ACAACUAU 6056 AUAGUUGU A G=GUC 640 5635 CCAGAUGG CUGAUGAG X CGAA ACUGUCCU 6057 AGGACAGU C CCAUCUGG 645 5636 GCUGUCCA CUGAUGAG X CGAA AUGGGACU 6058 AGUCCCAU C UGGACAGC Table VI. Hammerhe@ Ribozymes to IRF-2 659 5637 XCGAAAUGUUGCU6059AGCAACAUUGAGAAUCACUGAUGAG AAUCUCUUCUGAUGAGXCGAAAUUCUCAA6060UUGAGAAUCAAGAGAUU6665638 674 5639 UUGGUGAC CUGAUGAG X CGAA AUCUCUUG 6061 CAAGAGAU U GUCACCAA 677 5640 GGAUUGGU CUGAUGAG X CGAA ACAAUCUC 6062 GAGAUUGU C ACCAAUCC 684 5641 GUCUGGCG CUGAUGAG X CGAA AUUGGUGA 6063 UCACCAAU C CGCCAGAC ACUUGGCACUGAUGAGXCGAAAUGUCUGG6064CCAGACAUUUGCCAAGU6955642 AACUUGGCCUGAUGAGXCGAAAAUGUCUG6065CAGACAUUUGCCAAGUU6965643 ACCUCUACCUGAUGAGXCGAAACUUGGCA6066UGCCAAGUUGUAGAGGU7045644 GUCACCUCCUGAUGAGXCGAAACAACUUG6067CAAGUUGUAGAGGUGAC7075645 CUCAUGCUCUGAUGAGXCGAAACCGGCUG6068CAGCCGGUCAGCAUGAG7405646 755 5647 AGAGGGUA CUGAUGAG X CGAA AGCUCGCU 6069 AGCGAGCU C UACCCUCU GCAGAGGGCUGAUGAGXCGAAAGAGCUCG6070CGAGCUCUACCCUCUGC7575648 GAUCUGCACUGAUGAGXCGAAAGGGUAGA6071UCUACCCUCUGCAGAUC7625649 770 5650 ACGGGGGA CUGAUGAG X CGAA AUCUGCAG 6072 CUGCAGAU C UCCCCCGU 772 5651 ACACGGGG CUGAUGAG X CGAA AGAUCUGC 6073 GCAGAUCU C CCCCGUGU 781 5652 CAUAGGAA CUGAUGAG X CGAA ACACGGGG 6074 CCCCGUGU C UUCCUAUG 783 5653 UGCAUAGG CUGAUGAG X CGAA AGACACGG 6075 CCGUGUCU U CCUAUGCA 784 5654 CUGCAUAG CUGAUGAG X CGAA AAGACACG 6076 CGUGUCUU C CUAUGCAG 787 5655 UUUCUGCA CUGAUGAG X CGAA AGGAAGAC 6077 GUCUUCCU A UGCAGAAA 810 5656 GGGCACAC CUGAUGAG X CGAA AUCAGUCG 6078 CGACUGAU A GUGUGCCC 867 5657 GCCUUCAA CUGAUGAG X CGAA AUUCCUCU 6079 AGAGGAAU A UUGAAGGC 869 5658 UUGCCUUC CUGAUGAG X CGAA ACUGUUUG 6080 AGGAAUAU U GAAGGCAA 883 5659 UGCUGAGG CUGAUGAG X CGAA ACUGUUUG 6081 CAAACAGU A CCUCAGCA 887 5660 AUGUUGCU CUGAUGAG X CGAA AGGUACUG 6082 CAGUACCU C AGCAACAU 903 5661 GGAGCCUC CUGAUGAG X CGAA AGUCCCCA 6083 UGGGGACU C GAGGCUCC 910 5662 GCAGGUAG CUGAUGAG X CGAA AGCCUCGA 6084 UCGAGGCU C CUACCUGC 913 5663 GCAGCAGG CUGAUGAG X CGAA AGGAGCCU 6085 AGGCUCCU A CCUGCUGC 934 5664 UGACGAAG CUGAUGAG X CGAA ACGCCAUG 6086 CAUGGCGU C CUUCGUCA 937 CUGAUGAGXCGAAAGGACGCC6087GGCGUCCUUCGUCACUUAAGUGACG 938 5666 GAAGUGAC CUGAUGAG X CGAA AAGGACGC 6088 GCGUCCUU C GUCACUUC 941 5667 UUGGAAGU CUGAUGAG X CGAA ACGAAGGA 6089 UCCUUCGU C ACUUCCAA UUUGUUGGCUGAUGAGXCGAAAGUGACGA6090UCGUCACUUCCAACAAA9455668 946 5669 GUUUGUUG CUGAUGAG X CGAA AAGUGACG 6091 CGUCACUU C CAACAAAC 962 5670 GUGACCUG CUGAUGAG X CGAA AGGUCCGG 6092 CCGGACCU C CAGGUCAC 968 5671 UUGAUGGU CUGAUGAG X CGAA ACCUGGAG 6093 CUCCAGGU C ACCAUCAA 974 5672 UCCUCUUU CUGAUGAG X CGAA AUGGUGAC 6094 GUCACCAU C AAAGAGGA 990 5673 AGGCACCG CUGAUGAG X CGAA AUUGCUCU 6095 AGAGCAAU C CGGUGCCU 999 5674 GCUGUUGU CUGAUGAG X CGAA AGGCACCG 6096 CGGUGCCU U ACCAACAGC AGCUGUUGCUGAUGAGXCGAAAAGGCACC6097GGUGCCUUACAACAGCU10005675 1009 CUGAUGAGXCGAAAGCUGUUG6098CAACAGCUCCUGGCCCCGGGGCCAG 1020 5677 GUCUUGAA CUGAUGAG X CGAA AGGGGGCC 6099 GGCCCCCU U UUCAAGAC 1021 CUGAUGAGXCGAAAAGGGGGC6100GCCCCCUUUUCAAGAOCGGUCUUGA AGGUCUUGCUGAUGAGXCGAAAAAGGGGG6101CCCCCUUUUCAAGACCU10225679 GAGGUCUUCUGAUGAGXCGAAAAAAGGGG6102CCCCUUUUCAAGACCUC10235680 1031 5681 GAAAGGGG CUGAUGAG X CGAA AGGUCUUG 6103 CAAGACCU C CCCCUUUC GAGGAAGACUGAUGAGXCGAAAGGGGGAG6104CUCCCCCUUUCUUCCUC10375682 1038 5683 GGAGGAAG CUGAUGAG X CGAA AAGGGGGA 6105 UCCCCCUU U CUUCCUCC Table VI. Hammerhe. @bozymes to IRF-2 1039 5684 UGGAGGAA CUGAUGAG X CGAA AAAGGGGG 6106 CCCCCUUU U UUCCUCCA 1041 5685 XCGAAAGAAAGGG6107CCCUUUCUUCCUCCAUGCUGAUGAG 1042 5686 XCGAAAAGAAAGG6108CCUUUCUUCCUCCAUGACUGAUGAG 1045 CUGAUGAGXCGAAAGGAAGAA6109UUCUUCCUCCAUGACCCGGGUCAUG 1060 5688 UGCUGCUG CUGAUGAG X CGAA AUGCUGGG 6110 CCCAGCAU C CAGCAGCA GUCUGGCCCUGAUGAGXCGAAACUGCUGC6111GCAGCAGUCGGCCAGAC10715689 UUCUUGAUCUGAUGAGXCGAAACGCUGGC6112GCCAGCGUCAUCAAGAA11005690 1103 5691 GUUUUCUU CUGAUGAG X CGAA AUGACGCU 6113 AGCGUCAU C AAGAAAAC UGAUAUCCCUGAUGAGXCGAAAUGUUUUC6114GAAAACAUCGGAUAUCA11145692 CUGGGUGACUGAUGAGXCGAAAUCCGAUG6115CAUCGGAUAUCACCCAG11195693 GCCUGGGUCUGAUGAGXCGAAAUAUCCGA6116UCGGAUAUCACCCAGGC11215694 CAGCUCUUCUGAUGAGXCGAAACGCGGGC6117GCCCGCGUCAAGAGCUG11365695 AGAGGCUUCUGAUGAGXCGAAACAGCUCU6118AGAGCUGUUAAGCCUCU11465696 CAGAGGCUCUGAUGAGXCGAAAACAGCUC6119GAGCUGUUAAGCCUCUG11475697 GAGAGUCACUGAUGAGXCGAAAGGCUUAA6120UUAAGCCUCUGACUCUC11535698 1159 5699 XCGAAAGUCAGAG6121CUCUGACUCUCCGCGGUCUGAUGAG CCACCGCGCUGAUGAGXCGAAAGAGUCAG6122CUGACUCUCCGCGGUGG11615700 GCCCCAACCUGAUGAGXCGAAACCACCGC6123GCGGUGGUUGUUGGGGC11715701 GAAGCCCCCUGAUGAGXCGAAACAACCAC6124GUGGUUGUUGGGGCUUC11745702 AAGCCAAGCUGAUGAGXCGAAAGCCCCAA6125UUGGGGCUUCUUGGCUU11815703 1182 CUGAUGAGXCGAAAAGCCCCA6126UGGGGCUUCUUGGCUUUAAAGCCAA ACAAAGCCCUGAUGAGXCGAAAGAAGCCC6127GGGCUUCUUGGCUUUGU11845705 ACAAAACACUGAUGAGXCGAAAGCCAAGA6128UCUUGGCUUUGUUUUGU11895706 AACAAAACCUGAUGAGXCGAAAAGCCAAG6129CUUGGCUUUGUUUUGUU11905707 1193 5708 AACAACAA CUGAUGAG X CGAA ACAAAGCC 6130 GGCUUUGU U UUGUUGUU AAACAACACUGAUGAGXCGAAAACAAAGC6131GCUUUGUUUUGUUGUUU11945709 CAAACAACCUGAUGAGXCGAAAAACAAAG6132CUUUGUUUUGUUGUUUG11955710 AAACAAACCUGAUGAGXCGAAACAAAACA6133UGUUUUGUUGUUUGUUU11985711 1201 5712 UACAAACA CUGAUGAG X CGAA ACAACAAA 6134 UUUGUUGU U UGUUUGUA AUACAAACCUGAUGAGXCGAAAACAACAA6135UUGUUGUUUGUUUGUAU12025713 AAAAUACACUGAUGAGXCGAAACAAACAA6136UUGUUUGUUUGUAUUUU12055714 1206 CUGAUGAGXCGAAAACAAACA6137UGUUUGUUUGUAUUUUAUAAAAUAC AAAUAAAACUGAUGAGXCGAAACAAACAA6138UUGUUUGUAUUUUAUUU12095716 1211 5717 XCGAAAUACAAAC6139GUUUGUAUUUUAUUUUUCUGAUGAG 1212 5718 XCGAAAAUACAAA6140UUUGUAUUUUAUUUUUUCUGAUGAG AAAAAAAUCUGAUGAGXCGAAAAAUACAA6141UUGUAUUUUAUUUUUUU12135719 1214 5720 GAAAAAAA CUGAUGAG X CGAA AAAAUACA 6142 UGUAUUUU A UUUUUUUC 1216 CUGAUGAGXCGAAAUAAAAUA6143UAUUUUAUUUUUUUCUCGAGAAAAA AGAGAAAACUGAUGAGXCGAAAAUAAAAU6144AUUUUAUUUUUUUCUCU12175722 GAGAGAAACUGAUGAGXCGAAAAAUAAAA6145UUUUAUUUUUUUCUCUC12185723 1219 5724 XCGAAAAAAUAAA6146UUUAUUUUUUUCUCUCUCUGAUGAG 1220 CUGAUGAGXCGAAAAAAAUAA6147UUAUUUUUUUCUCUCUGCAGAGAGA UCAGAGAGCUGAUGAGXCGAAAAAAAAUA6148UAUUUUUUUCUCUCUGA12215726 1222 5727 GUCAGAGA CUGAUGAG X CGAA AAAAAAAU 6149 AUUUUUUU C UCUCUGAC 1224 5728 XCGAAAGAAAAAA6150UUUUUUCUCUCUGACACCUGAUGAG AGGUGUCACUGAUGAGXCGAAAGAGAAAA6151UUUUCUCUCUGACACCU12265729 GUCUAAAACUGAUGAGXCGAAAGGUGUCA6152UGACACCUAUUUUAGAC12355730 Table VI. Hammerh. tibozymes to IRF-2 UUGUCUAACUGAUGAGXCGAAAUAGGUGU6153ACACCUAUUUUAGACAA12375731 1238 5732 UUUGUCUA CUGAUGAG X CGAA AAUAGGUG 6154 CACCUAUU U UAGACAAA 1239 5733 AUUUGUCU CUGAUGAG X CGAA AAAUAGGU 6155 ACCUAUUU U AGACAAAU GAUUUGUCCUGAUGAGXCGAAAAAAUAGG6156CCUAUUUUAGACAAAUC12405734 UUCCCUUACUGAUGAGXCGAAAUUUGUCU6157AGACAAAUCUAAGGGAA12485735 UUUUCCCUCUGAUGAGXCGAAAGAUUUGU6158ACAAAUCUAAGGGAAAA12505736 CUAUUGUCCUGAUGAGXCGAAAGGCUUUU6159AAAAGCCUUGACAAUAG12645737 1271 5738 CAAUGUUC CUGAUGAG X CGAA AUUGUCAA 6160 UUGACAAU A GAACAUUG CAGCAAUCCUGAUGAGXCGAAAUGUUCUA6161UAGAACAUUGAUUGCUG12785739 GACACAGCCUGAUGAGXCGAAAUCAAUGU6162ACAUUGAUUGCUGUGUC12825740 UGGAGUUGCUGAUGAGXCGAAACACAGCA6163UGCUGUGUCCAACUCCA12905741 AGGUACUGCUGAUGAGXCGAAAGUUGGAC6164GUCCAACUCCAGUACCU12965742 GCUCCAGGCUGAUGAGXCGAAACUGGAGU6165ACUCCAGUACCUGGAGC13015743 UUAAAGAGCUGAUGAGXCGAAAGCUCCAG6166CUGGAGCUUCUCUUUAA13115744 1312 5745 GUUAAAGA CUGAUGAG X CGAA AAGCUCCA 6167 UGGAGCUU C UCUUUAAC GAGUUAAACUGAUGAGXCGAAAGAAGCUC6168GAGCUUCUCUUUAACUC13145746 1316 5747 CUGAGUUA CUGAUGAG X CGAA AGAGAAGC 6169 GCUUCUCU U UAACUCAG CCUGAGUUCUGAUGAGXCGAAAAGAGAAG6170CUUCUCUUUAACUCAGG13175748 1318 5749 XCGAAAAAGAGAA6171CUUUAACUCAGGACUCCCUGAUGAG 1322 5750 XCGAAAGUUAAAG6172CUUUAACUCAGGACUCCCUGAUGAG 1329 5751 XCGAAAGUCCUGA6173UCAGGACUCCAGCCCAUCUGAUGAG CGUCUACCCUGAUGAGXCGAAAUGGGCUG6174CAGCCCAUUGGUAGACG13385752 1342 5753 CACACGUC CUGAUGAG X CGAA ACCAAUGG 6175 CCAUUGGU A GACGUGUG GCUCUAGACUGAUGAGXCGAAACACACGU6176ACGUGUGUUUCUAGAGC13525754 1353 5755 GGCUCUAG CUGAUGAG X CGAA AACACACG 6177 CGUGUGUU U CUAGAGCC AGGCUCUACUGAUGAGXCGAAAAACACAC6178GUGUGUUUCUAGAGCCU13545756 GCAGGCUCCUGAUGAGXCGAAAGAAACAC6179GUGUUUCUAGAGCCUGC13565757 CCCUGGGACUGAUGAGXCGAAAUCCAGCA6180UGCUGGAUCUCCCAGGG13705758 AGCCCUGGCUGAUGAGXCGAAAGAUCCAG6181CUGGAUCUCCCAGGGCU13725759 UGAGUGAGCUGAUGAGXCGAAAGCCCUGG6182CCAGGGCUACUCACUCA13815760 ACUUGAGUCUGAUGAGXCGAAAGUAGCCC6183GGGCUACUCACUCAAGU13845761 UUGAACUUCUGAUGAGXCGAAAGUGAGUA6184UACUCACUCAAGUUCAA13885762 GGUCCUUGCUGAUGAGXCGAAACUUGAGU6185ACUCAAGUUCAAGGACC13935763 UGGUCCUUCUGAUGAGXCGAAAACUUGAG6186CUCAAGUUCAAGGACCA13945764 CCGCAGGCCUGAUGAGXCGAAAUGCAGCA6187UGCUGCAUUGCCUGCGG14275765 CUGGCCUUCUGAUGAGXCGAAACCGCAGG6188CCUGCGGUCAAGGCCAG14375766 UCCGUUCUCUGAUGAGXCGAAAGGCAUCC6189GGAUGCCUCAGAACGGA14655767 GUUCACAUCUGAUGAGXCGAAAUCUCGUC6190GACGAGAUAAUGUGAAC14805768 AUUCCAGCCUGAUGAGXCGAAAGUUCACA6191UGUGAACUAGCUGGAAU14905769 1499 5770 XCGAAAUUCCAGC6192GCUGGAAUUUUUUAUUCCUGAUGAG 1500 5771 AGAAUAAACUGAUGAG X 6193CUGGAAUUUUUUAUUCUAAUUCCAG AAGAAUAACUGAUGAGXCGAAAAAUUCCA6194UGGAAUUUUUUAUUCUU15015772 CAAGAAUACUGAUGAGXCGAAAAAAUUCC6195GGAAUUUUUUAUUCUUG15025773 1503 5774 XCGAAAAAAAUUC6196GAAUUUUUUAUUCUUGUCUGAUGAG CACAAGAACUGAUGAGXCGAAAAAAAAUU6197AAUUUUUUAUUCUUGUG15045775 1506 CUGAUGAGXCGAAAUAAAAAA6198UUUUUUAUUCUUGUGAAUUCACAAG AUUCACAACUGAUGAGXCGAAAAUAAAAA6199UUUUUAUUCUUGUGAAU15075777 Table VI. Hammerhe ibozymes to IRF-2 1509 5778 AUAUUCAC CUGAUGAG X CGAA AGAAUAAA 6200 UUUAUUCU U GUGAAUAU UAUGUACACUGAUGAGXCGAAAUUCACAA6201UUGUGAAUAUGUACAUA15165779 UGCCUAUGCUGAUGAGXCCAAACAUAUUC6202GAAUALGUACAUAGGCA15205780 GUGCUGCCCUGAUGAGXCGAAAUGUACAU6203AUGUACAUACGCAGCAC15245781 1534 5782 XCGAAAGUGCUGC6204GCAGCACUAGCGACAUUCUGAUGAG CAGACUGCCUGAUGAGXCGAAAUGUCGCU6205AGCGACAUUGCAGUCUG15425783 CAGAAGCACUGAUGAGXCGAAACUGCAAU6206AUUGCAGUCUGCUUCUG15485784 AGGUGCAGCUGAUGAGXCGAAAGCAGACU6207AGUCUGCUUCUGCACCU15535785 AAGGUGCACUGAUGAGXCGAAAAGCAGAC6208GUCUGCUUCUGCACCUU15545786 UUUAAGAUCUGAUGAGXCGAAAGGUGCAG6209CUGCACCUUAUCUUAAA15625787 CUUUAAGACUGAUGAGXCGAAAAGGUGCA6210UGCACCUUAUCUUAAAG15635788 UGCUUUAACUGAUGAGXCGAAAUAAGGUG6211CACCUUAUCUUAAAGCA15655789 AGUGCUUUCUGAUGAGXCGAAAGAUAAGG6212CCUUAUCUUAAAGCACU15675790 1568 5791 AAGUGCUUCUGAUGAG X 6213CUUAUCUUAAAGCACUUAAGAUAAG CUAUCUGUCUGAUGAGXCGAAAGUGCUUU6214AAAGCACUUACAGAUAG15765792 1577 5793 CCUAUCUG CUGAUGAG X CGAA AAGUGCUU 6215 AAGCACUU A CAGAUAGG 1583 5794 AGAAGGCC CUGAUGAG X CGAA AUCUGUAA 6216 UUACAGAU A GGCCUUCU 1589 5795 AUCACAAG CUGAUGAG X CGAA AGGCCUAU 6217 AUAGGCCU U CUUGUGAU 1590 5796 XCGAAAAGGCCUA6218UAGGCCUUCUUGUGAUCCUGAUGAG 1592 5797 AAGAUCAC CUGAUGAG X CGAA AGAAGGCC 6219 GGCCUUCU U GUGAUCUU 1598 5798 UAGAGCAA CUGAUGAG X CGAA AUCACAAG 6220 CUUGUGAU C UUGCUCUA GAUAGAGCCUGAUGAGXCGAAAGAUCACA6221UGUGAUCUUGCUCUAUC16005799 1604 5800 GUGAGAUA CUGAUGAG X CGAA AGCAAGAU 6222 AUCUUGCU C UAUCUCAC 1606 5801 CUGUGAGA CUGAUGAG X CGAA AGAGCAAG 6223 CUUGCUCU A UCUCACAG 1608 5802 UGCUGUGA CUGAUGAG X CGAA AUAGAGCA 6224 UGCUCUAU C UCACAGCA 1610 5803 UGUGCUGU CUGAUGAG X CGAA AGAUAGAG 6225 CUCUAUCU C ACAGCACA 1621 5804 GGGGUGCU CUGAUGAG X CGAA AGUGUGCU 6226 AGCACACU C AGCACCCC 1632 5805 GGGCAGAG CUGAUGAG X CGAA AGGGGGUG 6227 CACCCCCU U CUCUGCCC 1633 5806 UGGGCAGA CUGAUGAG X CGAA AAGGGGGU 6228 ACCCCCUU C UCUGCCCA 1635 5807 AAUGGGCA CUGAUGAG X CGAA AGAAGGGG 6229 CCCCUUCU C UGCCCAUU 1643 5808 GGCUGGGG CUGAUGAG X CGAA AUGGGCAG 6230 CUGCCCAU U CCCCAGCC 1644 5809AGGCUGGG CUGAUGAG X CGAA AAUGGGCA 6231 UGCCCAUU C CCCAGCCU 1653 CUGAUGAGXCGAAAGGCUGGG6232CCCAGCCUCUCUUCCUAUAGGAAGA GAUAGGAACUGAUGAGXCGAAAGAGGCUG6233CAGCCUCUCUUCCUAUC16555811 1657 5812 XCGAAAGAGAGGC6234GCCUCUCUUCCUAUCCCCUGAUGAG 1658 5813 XCGAAAAGAGAGG6235CCUCUCUUCCUAUCCCACUGAUGAG 1661 5814GGAUGGGA CUGAUGAG X CGAA AGGAAGAG 6236 CUCUUCCU A UCCCAUCC 1663 5815 UGGGAUGG CUGAUGAG X CGAA AUAGGAAG 6237 CUUCCUAU C CCAUCCCA 1668 5816 UGGGAUGG CUGAUGAG X CGAA AUGGGAUA 6238 UAUCCCAU C CCAUCCCA 1673 5817 UGGGAUGG CUGAUGAG X CGAA AUGGGAUG 6239 CAUCCCAU C CCAUCCCA 1678 5818 UGGGAUGG CUGAUGAG X CGAA AUGGGAUG 6240 CAUCCCAU C CCAUCCCA 1683 5819 UGGGAUGG CUGAUGAG X CGAA AUGGGAUG 6241 CAUCCCAU C CCAUCCCA 1688 5820 UGGGAUGG CUGAUGAG X CGAA AUGGGAUG 6242 CAUCCCAU C CCAUCCCA 1693 5821 CGGGAUGG CUGAUGAG X CGAA AUGGGAUG 6243 CAUCCCAU C CCAUCCCG 1698 5822 AAGAGCGG CUGAUGAG X CGAA AUGGGAUG 6244 CAUCCCAU C CCGCUCUU 1704 5823 UAGGAAAA CUGAUGAG X CGAA AGCGGGAU 6245 AUCCCGCU C UUUUCCUA 1706 5824 AGUAGGAA CUGAUGAG X CGAA AGAGCGGG 6246 CCCGCUCU U UUCCUACU Table VI. Hammerhe_. tibozymes to IRF-2 AAGUAGGACUGAUGAGXCGAAAAGAGCGG6247CCGCUCUUUUCCUACUU17075825 AAAGUAGGCUGAUGAGXCGAAAAAGAGGG6248CGCUCUUUUCCUACUUU17085826 1709 5827 XCGAAAAAAGAGC6249GCUCUUUUCCUACUUUUCUGAUGAG 1712 5828 XCGAAAGGAAAAG6250CUUUUCCUACUUUUCCUCUGAUGAG GGAAGGAACUGAUGAGXCGAAAGUAGGAA6251UUCCUACUUUUCCUUCC17155829 1716 5830 GGGAAGGA CUGAUGAG X CGAA AAGUAGGA 6252 UCCUACUU U UCCUUCCC 1717 5831 AGGGAAGG CUGAUGAG X CGAA AAAGUAGG 6253 CCUACUUU U CCUUCCCU 1718 5832 GAGGGAAG CUGAUGAG X CGAA AAAAGUAG 6254 CUACUUUU C CUUCCCUC UUUGAGGGCUGAUGAGXCGAAAGGAAAAG6255CUUUUCCUUCCCUCAAA17215833 CUUUGAGGCUGAUGAGXCGAAAAGGAAAA6256UUUUCCUUCCCUCAAAG17225834 GAAGCUUUCUGAUGAGXCGAAAGGGAAGG6257CCUUCCCUCAAAGCUUC17265835 UGGAAUGGCUGAUGAGXCGAAAGCUUUCA6258UCAAAGCUUCCAUUCCA17335836 1734 5837 GUGGAAUG CUGAUGAG X CGAA AAGCUUUG 6259 CAAAGCUU C CAUUCCAC GGAUGUGGCUGAUGAGXCGAAAUGGAAGC6260GCUUCCAUUCCACAUCC17385838 1739 5839 CGGAUGUG CUGAUGAG X CGAA AAUGGAAG 6261 CUUCCAUU C CACAUCCG CUCCUCCGCUGAUGAGXCGAAAUGUGGAA6262UUCCACAUCCGGAGGAG17455840 1769 5841 XCGAAAUUCAUUU6263AAAUGAAUUUCUCUACACUGAUGAG CUGUAGAGCUGAUGAGXCGAAAAUUCAUU6264AAUGAAUUUCUCUACAG17705842 UCUGUAGACUGAUGAGXCGAAAAAUUCAU6254AUGAAUUUCUCUACAGA17715843 1773 5844 XCGAAAGAAAUUC6266GAAUUUCUCUACAGAUGCUGAUGAG 1775 5845 XCGAAAGAGAAAU6267AUUUCUCUACAGAUGUCCUGAUGAG GAAAAUGGCUGAUGAGXCGAAACAUCUGU6268ACAGAUGUCCCAUUUUC17835846 AGUCUGAACUGAUGAGXOCAAAUGGGACA6269UGUCCCAUUUUCAGACU17885847 1789 5848 XCGAAAAUGGGAC6270GUCCCAUUUUCAGACUGCUGAUGAG GCAGUCUGCUGAUGAGXCGAAAAADGGGA6271UCCCAUUUUCAGACUGC17905849 AGCAGUCUCUGAUGAGXCGAAAAAAUGGG6272CCCAUUUUCAGACUGCU17915850 UUUUUUUACUGAUGAGXCGAAAGCAGUCU6273AGACUGCUUUAAAAAAA18005851 UUUUUUUUCUGAUGAGXCGAAAAGCAGUC6274GACUGCUUUAAAAAAAA18015852 AUUUUUUUCUGAUGAGXCGAAAAAGCAGU6275ACUGCUUUAAAAAAAAU18025853 AUUAGAAGCUGAUGAGXCGAAAUUUUUUU6276AAAAAAAUCCUUCUAAU18115854 CAGAUUAGCUGAUGAGXCGAAAGGAUUUU6277AAAAUCCUUCUAAUCUG18145855 1815 5856 GCAGAUUA CUGAUGAG X CGAA AAGGAUUU 6278 AAAUCCUU C UAAUCUGC 1817 5857 XCGAAAGAAGGAU6279AUCCUUCUAAUCUGCUACUGAUGAG GCAUAGCACUGAUGAGXCGAAAUUAGAAG6280CUUCUAAUCUGCUAUGC18205858 1825 5859 XCGAAAGCAGAUU6281AAUCUGCUAUGCUUGAACUGAUGAG UGGCAUUCCUGAUGAGXCGAAAGCAUAGC6282GCUAUGCUUGAAUGCCA18305860 UUCCUUUGCUGAUGAGXCGAAACCGCGUG6283CACGCGGUACAAAGGAA18455861 UUCCAUGACUGAUGAGXCGAAACUUUUUC6284GAAAAAGUAUCAUGGAA18595862 AUUUCCAUCUGAUGAGXCGAAAUACUUUU6285AAAAGUAUCAUGGAAAU18615863 UUGCAUAACUGAUGAGXCGAAAUUUCCAU6286AUGGAAAUAUUAUGCAA18705864 AUUUGCAUCUGAUGAGXCGAAAUAUUUCC6287GGAAAUAUUAUGCAAAU18725865 AAUUUGCACUGAUGAGXCGAAAAUAUUUC6288GAAAUAUUAUGCAAAUU18735866 AAUCUGGGCUGAUGAGXCGAAAUUUGCAU6289AUGCAAAUUCCCAGAUU18815867 1882 5868 AAAUCUGG CUGAUGAG X CGAA AAUUUGCA 6290 UGCAAAUU C CCAGAUUU UGUCUUCACUGAUGAGXCGAAAUCUGGGA6291UCCCAGAUUUGAAGACA18895869 UUGUCUUCCUGAUGAGXCGAAAAUCUGGG6292CCCAGAUUUGAAGACAA18905870 AAUUAGAGCUGAUGAGXCGAAAUUUUUGU6293ACAAAAAUACUCUAAUU19035871 Table VI. Hammerhe. ibozymes to IRF-2 1906 5872 UAGAAUUA CUGAUGAG X CGAA AGUAUUUU 6294 AAAAUACU C UAAUUCUA GUUAGAAUCUGAUGAGXCGAAAGAGUAUU6295AAUACUCUAAUUCUAAC19085873 CUGGUUAGCUGAUGAGXCGAAAUUAGAGU6296ACUCUAAUUCUAACCAG19115874 UCUGGUUACUGAUGAGXCGAAAAUUAGAG6297CUCUAAUUCUAACCAGA19125875 GCUCUGGUCUGAUGAGXCGAAAGAAUUAG6298CUAAUUCUAACCAGAGC19145876 AAAUAAAACUGAUGAGXCGAAAGCUUGCU6299AGCAAGCUUUUUUAUUU19285877 AAAAUAAACUGAUGAGXCGAAAAGCUUGC6300GCAAGCUUUUUUAUUUU19295878 AAAAAUAACUGAUGAGXCGAAAAAGCUUG6301CAAGCUUUUUUAUUUUU19305879 AAAAAAUACUGAUGAGXCGAAAAAAGCUU6302AAGCUUUUUUAUUUUUU19315880 1932 5881 XCGAAAAAAAGCU6303AGCUUUUUUAUUUUUUACUGAUGAG AUAAAAAACUGAUGAGXCGAAAAAAAAGC6304GCUUUUUUAUUUUUUAU19335882 1935 8553 XCGAAAUAAAAAA6305UUUUUUAUUUUUUAUACCUGAUGAG 1936 5884 XCGAAAAUAAAAA6306UUUUUAUUUUUUAUACACUGAUGAG 1937 CUGAUGAGXCGAAAAAUAAAA6307UUUUAUUUUUUAUACAGCUGUAUAA 1938 5886 CCUGUAUA CUGAUGAG X CGAA AAAAUAAA 6308 UUUAUUUU U UAUACAGG 1939 5887 CCCUGUAU CUGAUGAG X CGAA AAAAAUAA 6309 UUAUUUUU U AUACAGGG 1940 5888 CCCCUGUA CUGAUGAG X CGAA AAAAAAUA 6310 UAUUUUUU A UACAGGGG 1942 5889 UUCCCCUG CUGAUGAG X CGAA AUAAAAAA 6311 UUUUUUAU GAGGGGAA 1952 4890 GAAUAAAA CUGAUGAG X CGAA AUUCCCCU 6312 AGGGGAAU A UUUUAUUC 1954 5891 UUGAAUAA CUGAUGAG X CGAA AUAUUCCC 6313 GGGAAUAU UUAUUCAA 1955 5892 CUUGAAUA CUGAUGAG X CGAA AAUAUUCC 6314 GGAAUAUU U UAUUCAAG 1956 5893 CCUUGAAU CUGAUGAG X CGAA AAAUAUUC 6315 GAAUAUUU U AUUCAAGG 1957 5894 ACCUUGAA CUGAUGAG X CGAA AAAAUAUU 6316 AAUAUUUU A UUCAAGGU 1959 5895 UUACCUUG CUGAUGAG X CGAA AUAAAAUA 6317 UAUUUUAU U CAAGGUAA 1960 5896 UUUACCUU CUGAUGAG X CGAA AAUAAAAU 6318 AUUUUAUU C AAGGUAAA 1966 5897 UAGAAUUU CUGAUGAG X CGAA ACCUUGAA 6319 UUCAAGGU A AAAUUCUA 1971 5898 UUAUUUAG CUGAUGAG X CGAA AUUUUACC 6320 GGUAAAAU U CUAAAUAA 1972 5899 UUUAUUUA CUGAUGAG X CGAA AAUUUUAC 6321 GUAAAAUU C UAAAUAAA 1974 5900 AUUUUAUU CUGAUGAG X CGAA AGAAUUUU 6322 AAAAUUCU A AAUAAAAU 1978 5901 UUAUAUUU CUGAUGAG X CGAA AUUUAGAA 6323 UUCUAAAU A AAAUAUAA 1983 CUGADGAGXCGAAAUUUUAUU6324AAUAAAAUAUAAUUGUUAACAAUUA AAAACAAUCUGAUGAGXCGAAAUAUUUUA6325UAAAAUAUAAUUGUUUU19855903 1988 5904 UAAAAAAC CUGAUGAG X CGAA AUUAUAUU 6326 AAUAUAAU U GUUUUUUA AGAUAAAACUGAUGAGXCGAAACAAUUAU6327AUAAUUGUUUUUUAUCU19915905 1992 5906 AAGAUAAA CUGAUGAG X CGAA AACAAUUA 6328 UAAUUGUU U UUUAUCUU 1993 5907 AAAGAUAA CUGAUGAG X CGAA AAACAAUU 6329 AAUUGUUU U UUAUCUUU 1994 5908 AAAAGAUA CUGAUGAG X CGAA AAAACAAU 6330 AUUGUUUU U UAUCUUUU 1995 5909 GAAAAGAU CUGAUGAG X CGAA AAAAACAA 6331 UUGUUUUU U AUCUUUUC 1996 5910 AGAAAAGA CUGAUGAG X CGAA AAAAAACA 6332 UGUUUUUU A UCUUUUCU 1998 5911 GUAGAAAA CUGAUGAG X CGAA AUAAAAAA 6333 UUUUUUAU C UUUUCUAC 2000 5912 CUGUAGAA CUGAUGAG X CGAA AGAUAAAA 6334 UUUUAUCU U UUCUACAG 2001 5913 GCUGUAGA CUGAUGAG X CGAA AAGAUAAA 6335 UUUAUCUU U UCUACAGC 2002 5914 UGCUGUAG CUGAUGAG X CGAA AAAGAUAA 6336 UUAUCUUU U CUACAGCA 2003 5915 UUGCUGUA CUGAUGAG X CGAA AAAAGAUA 6337 UAUCUUUU C UACAGCAA 2005 5916 AUUUGCUG CUGAUGAG X CGAA AGAAAAGA 6338 UCUUUUCU A CAGCAAAU 2014 5917 AAAUUAUA CUGAUGAG X CGAA AUUUGCUG 6339 CAGCAAAU U UAUAAUUU 2015 5918 AAAAUUAU CUGAUGAG X CGAA AAUUUGCU 6340 AGCAAAUU U AUAAUUUU Table VI. Hammerhe lbozymes to IRF-2 UAAAAUUACUGAUGAGXCGAAAAAUUUGC6341GCAAAUUUAUAAUUUUA20165919 CUUAAAAUCUGAUGAGXCGAAAUAAAUUU6342AAAUUUAUAAUUUUAAG20185920 AAUCUUAACUGAUGAGXCGAAAUUAUAAA6343UUUAUAAUUUUAAGAUU20215921 GAAUCUUACUGAUGAGXCGAAAAUUAUAA6344UUAUAAUUUUAAGAUUC20225922 GGAAUCUUCUGAUGAGXCGAAAAAUUAUA6345UAUAAUUUUAAGAUUCC20235923 AGGAAUCUCUGAUGAGXCGAAAAAAUUAU6346AUAAUUUUAAGAUUCCU20245924 AGAAAAGGCUGAUGAGXCGAAAUCUUAAA6347UUUAAGAUUCCUUUUCU20295925 2030 5926 XCGAAAAUCUUAA6348UUAAGAUUCCUUUUCUUCUGAUGAG 2033 5927 XCGAAAGGAAUCU6349AGAUUCCUUUUCUUGUUCUGAUGAG AAACAAGACUGAUGAGXCGAAAAGGAAUC6350GAUUCCUUUUCUUGUUU20345928 UAAACAAGCUGAUGAGXCGAAAAAGGAAU6351AUUCCUUUUCUUGUUUA20355929 AUAAACAACUGAUGAGXCGAAAAAAGGAA6352UUCCUUUUCUUGUUUAU20365930 2038 5931 UGAUAAAC CUGAUGAG X CGAA AGAAAAGG 6353 CCUUUUCU U GUUUAUCA 2041 5932 UGCUGAUA CUGAUGAG X CGAA ACAAGAAA 6354 UUUCUUGU U UAUCAGCA CUGCUGAUCUGAUGAGXCGAAAACAAGAA6355UUCUUGUUUAUCAGCAG20425933 ACUGCUGACUGAUGAGXCGAAAAACAAGA6356UCUUGUUUAUCAGCAGU20435934 CAACUGCUCUGAUGAGXCGAAAUAAACAA6357UUGUUUAUCAGCAGUUG20455935 GUAAUAACCUGAUGAGXCGAAACUGCUGA6358UCAGCAGUUGUUAUUAC20525936 GAUGUAAUCUGAUGAGXCGAAACAACUGC6359GCAGUUGUUAUUACAUC20555937 GGAUGUAACUGAUGAGXCGAAAACAACUG6360CAGUUGUUAUUACAUCC20565938 AAGGAUGUCUGAUGAGXCGAAAUAACAAC6361GUUGUUAUUACAUCCUU20585939 2059 5940 CAAGGAUG CUGAUGAG X CGAA AAUAACAA 6362 UUGUUAUU A CAUCCUUG 2063 5941 GCCACAAG CUGAUGAG X CGAA AUGUAAUA 6363 UAUUACAU C CUUGUGGC UGUGCCACCUGAUGAGXCGAAAGGAUGUA6364UACAUCCUUGUGGCACA20665942 UAAAAAAACUGAUGAGXCGAAAUGUGCCA6365UGGCACAUUUUUUUUUA20765943 UUAAAAAACUGAUGAGXCGAAAAUGUGCC6366GGCACAUUUUUUUUUAA20775944 AUUAAAAACUGAUGAGXCGAAAAAUGUGC6367GCACAUUUUUUUUUAAU20785945 2079 5946 AAUUAAAACUGAUGAG X 6368CACAUUUUUUUUUAAUUAAAAUGUG AAAUUAAACUGAUGAGXCGAAAAAAAUGU6369ACAUUUUUUUUUAAUUU20805947 AAAAUUAACUGAUGAGXCGAAAAAAAAUG6370CAUUUUUUUUUAAUUUU20815948 CAAAAUUACUGAUGAGXCGAAAAAAAAAU6371AUUUUUUUUUAAUUUUG20825949 ACAAAAUUCUGAUGAGXCGAAAAAAAAAA6372UUUUUUUUUAAUUUUGU20835950 UACAAAAUCUGAUGAGXCGAAAAAAAAAA6373UUUUUUUUAAUUUUGUA20845951 2087 5952 CUUUACAA CUGAUGAG X CGAA AUUAAAAA 6374 UUUUUAAU U UUGUAAAG CCUUUACACUGAUGAGXCGAAAAUUAAAA6375UUUUAAUUUUGUAAAGG20885953 ACCUUUACCUGAUGAGXCGAAAAAUUAAA6376UUUAAUUUUGUAAAGGU20895954 2092 5955 XCGAAACAAAAUU6377AAUUUUGUAAAGGUGAACUGAUGAG 2108 5956 XCGAAAGCUUUUU6378AAAAAGCUUUUADGAGCCUGAUGAG AGCUCAUACUGADGAGXCGAAAAGCUUUU6379AAAAGCUUUUAUGAGCU21095957 GAGCUCAUCUGAUGAGXCGAAAAAGCUUU6380AAAGCUUUUAUGAGCUC21105958 UGAGCUCACUGAUGAGXCGAAAAAAGCUU6381AAGCUUUUAUGAGCUCA21115959 2118 5960 UGCUAGAU CUGAUGAG X CGAA AGCUCAUA 6382 UAUGAGCU C PLS 2121 5961 XCGAAAUGAGCUC6383GAGCUCAUCUAGCAAUCCUGAUGAG 2123 5962 XCGAAAGAUGAGC6384GCUCAUCUAGCAAUCAGCUGAUGAG GAAAAUCUCUGAUGAGXCGAAAUUGCUAG6385CUAGCAAUCAGAUUUUC21295963 CACAGGAACUGAUGAGXCGAAAUCUGAUU6386AAUCAGAUUUUCCUGUG21345964 CCACAGGACUGAUGAGXCGAAAAUCUGAU6387AUCAGAUUUUCCUGUGG21355965 Table VI. HammerL. tibozymes to IRF-2 UCCACAGGCUGAUGAGXCGAAAAAUCUGA6388UCAGAUUUUCCUGUGGA21365966 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.

Table VII. Hammerh. tibozymes to CDP Pos Seq.I.D.SubstrateRZ No.I.D.No. ACCUGGCACUGAUGAGXCGAAAGUCCCGG6929CCGGGACTCTGCCAGGT336389 GUACGCACCUGAUGAGXCGAAACAUCCAC6930GTGGATGTTGTGCGTAC486390 55 6391 XCGAAACGCACAA6931TTGTGCGTACGCGGAGCCUGAUGAG CUCUCUUCCUGAUGAGXCGAAACCUGGCU6932AGCCAGGTTGAAGAGAG696392 GUGGCAUCCUGAUGAGXCGAAAGUUCUCU6933AGAGAACTCGATGCCAC826393 UUCGCCAACUGAUGAGXCGAAACCGUUGC6934GCAACGGTATTGGCGAA1006394 GGUUCGCCCUGAUGAGXCGAAAUACCGUU6935AACGGTATTGGCGAACC1026395 GCUUUCUGCUGAUGAGXCGAAACUGCUCA6936TGAGCAGTCCAGAAAGC1326396 UGUUCGAUCUGAUGAGXCGAAAGCCGCUU6937AAGCGGCTTATCGAACA1456397 CUGUUCGACUGAUGAGXCGAAAAQCCQCU6938AGCGGCTTATCGAACAG1466398 CUCUGUUCCUGAUGAGXCGAAAUAAGCCG6939CGGCTTATCGAACAGAG1486399 165 6400 XCGAAACUCCCGG6940CCGGGAGTTCAAGAAGACUGAUGAG UUCUUCUUCUGAUGAGXCGAAAACUCCCG6941CGGGAGTTCAAGAAGAA1666401 179 CUGAUGAGXCGAAAGUGUUCU6942AGAACACTCCAGAGGATAUCCUCUG CUUGCGCACUGAUGAGXCGAAAUCCUCUG6943CAGAGGATTTGCGCAAG1886403 189 6404 GCUUGCGC CUGAUGAG X CGAA AAUCCUCU 6944 AGAGGATT T GCGCAAGC 202 6405 AGCGGCGC CUGAUGAG X CGAA ACCUGCUU 6945 AAGCAGGT A GCGCCGCT 221 6406 UCCUUGGA CUGAUGAG X CGAA ACUCUUCA 6946 TGAAGAGT T TCCAAGGA 222 6407 CUCCUUGG CUGAUGAG X CGAA AACUCUUC 6947 GAAGAGTT T CCAAGGAG 223 6408 UCUCCUUG CUGAUGAG X GCAA AAACUCUU 6948 AAGAGTTT C CAAGGAGA 235 6409 AGUGCAUC CUGAUGAG X CGAA AUCUCUCC 6949 GGAGAGAT T GATGCACT 248 6410 GCUUCUUU CUGAUGAG X CGAA ACUCAGUG 6950 CACTGAGT A AAAGAAGC 275 6411 AUUCAAGA CUGAUGAG X CGAA AGCUGCUU 6951 AAGCAGCT T TCTTGAAT 276 6412 CAUUCAAG CUGAUGAG X CGAA AAGCUGCU 6952 AGCAGCTT T CTTGAATG 277 6413ACAUUCAA CUGAUGAG X CGAA AAAGCUGC 6953 GCAGCTTT C TTGAATGT 279 6414 AGACAUUC CUGAUGAG X CGAA AGAAAGCU 6954 AGCTTTCT T GAATGTCT 286 6415 CUUUUGUA CUGAUGAG X CGAA ACAUUCAA 6955 TTGAATGT C TACAAAAC 288 6416 AUCUUUUG CUGAUGAG X CGAA AGACAUUC 6956 GAATGTCT A CAAAAGAT 297 6417 CGUCAAUC CUGAUGAG X CGAA AUCUUUUG 6957 CAAAAGAT T GATTGACG 301 6418 GGGACGUC CUGAUGAG X CGAA AUCAAUCU 6958 AGATTGAT T GACGTCCC 307 6419 GGAUCUGG CUGAUGAG X CGAA ACGUCAAU 6959 ATTGACGT C CCAGATCC 314 6420 UGGUACGG CUGAUGAG X CGAA AUCUGGGA 6960 TCCCAGAT C CCGTACCA 319 6421 AAAGCUGG CUGAUGAG X CGAA ACGGGAUC 6961 GATCCCGT A CCAGCTTT 326 6422 GAGAUCCA CUGAUGAG X CGAA AGCUGGUA 6962 TACCAGCT T TGGATCTC 327 6423 CGAGAUCC CUGAUGAG X CGAA AAGCUGGU 6963 ACCAGCTT T GGATCTCG 332 6424 CUGUCCGA CUGAUGAG X CGAA AUCCAAAG 6964 CTTTGGAT C TCGGACAG 334 6425 UGCUGUCC CUGAUGAG X CGAA AGAUCCAA 6965 TTGGATCT C QGACAGCA 346 6426 UUGAGCUG CUGAUGAG X CGAA AGUUGCUG 6966 CAGCAACT C CAGCTCAA 352 6427 UGCACUUU CUGAUGAG X CGAA AGCUGGAG 6967 CTCCAGCT C AAAGTGCA 374 6428 UGUUUCAA CUGAUGAG X CGAA AUCGUGCA 6968 TGCACGAT A TTGAAACA 376 6429 UCUGUUUC CUGAUGAG X CGAA AUAUCGUG 6969 CACGATAT T GAAACAGA 397 6430 GUUUCCCU CUGAUGAG X CGAA AGUUUCUG 6970 CAGAAACT T AGGGAAAC 398 6431 AGUUUCCC CUGAUGAG X CGAA AAGUUUCU 6971 AGAAACTT A GGGAAACT 407 6432 UUCUUCCA CUGAUGAG X CGAA AGUUUCCC 6972 GGGAAACT C TGGAAGAA 417 6433 CCUUGUUG CUGAUGAG X CGAA AUUCUUCC 6973 GGAAGAAT A CAACAAGG Table VII. Hammerhx Ribozymes to CDP 429 6434 CUUCAGCA CUGAUGAG X CGAA AUUCCUUG 6974 CAAGGAAT T TGCTGAAG CUUCAGCCCUGAUGAGXCGAAAAUUCCUU6975AAGGAATTTGCTGAAGT4306435 AACCUCUUCUGAUGAGXCGAAAUUUUUCA6976TGAAAAATCAAGAGGTT4466436 454 6437 XCGAAACCUCUUG6977CAAGAGGTTACGATAAACUGAUGAG UUUUAUCGCUGAUGAGXCGAAAACCUCUU6978AAGAGGTTACGATAAAA4556438 460 6439 XCGAAAUCGUAAC6979GTTACGATAAAAGCACTCUGAUGAG UUCUCUUUCUGAUGAGXCGAAAGUGCUUU6980AAAGCACTTAAAGAGAA4696440 470 6441 UUUCUCUU CUGAUGAG X CGAA AAGUGCUU 6981 AAGCACTT A AAGAGAAA UAUUCUCGCUGAUGAGXCGAAAUUUUCUC6982GAGAAAATCCGAGAATA4816442 489 6443 XCGAAAUUCUCGG6983CCGAGAATATGAACAGACUGAUGAG UCAAGAGCCUGAUGAGXCGAAAUGGUUUC6984GAAACCATAGCTCTTGA5236444 527 6445 CUUCUCAA CUGAUGAG X CGAA AGCUAUGG 6985 CCATAGCT C TTGAGAAG 529 6446 UCCUUCUC CUGAUGAG X CGAA AGAGCUAU 6986 ATAGCTCT T GAGAAGGA 546 6447 CAUUCUGU CUGAUGAG X CGAA ACUUCUGU 6987 ACAGAAGT T ACAGAATG 547 6448 UCAUUCUG CUGAUGAG X CGAA AACUUCUG 6988 CAGAAGTT A CAGAATGA 558 6449 UUUCUGCA CUGAUGAG X CGAA AGUCAUUC 6989 GAATGACT T TGCAGAAA 559 6450 UUUUCUGC CUGAUGAG X CGAA AAGUCADU 6990 AATGACTT T GCAGAAAA 597 6451 AGGUGGUG CUGAUGAG X CGAA ACAUCUGU 6991 ACAGATGT C CACCACCT 606 6452 CCAGCUUU CUGAUGAG X CGAA AGGUGGUG 6992 CACCACCT C AAAGCTGG 629 6453 CUGAACCU CUGAUGAG X CGAA AUGCUCAG 6993 CTGAGCAT A AGGTTCAG 634 6454 AGGCUCUG CUGAUGAG X CGAA ACCUUAUG 6994 CATAAGGT T CAGAGCCT 635 6455 UAGGCUCU CUGAUGAG X CGAA AACCUUAU 6995 ATAAGGTT C AGAGCCTA GCUGUUUGCUGAUGAGXCGAAAGGCUCUG6996CAGAGCCTACAAACAGC6436456 UUCUGUUCCUGAUGAGXCGAAAGUUUUUU6997AAAAAACTCGAACAGAA6656457 675 6458 XCGAAAUUCUGUU6998AACAGAATTATTTGACCCUGAUGAG AGGUCAAACUGAUGAGXCGAAAAUUCUGU6999ACAGAATTATTTGACCT6766459 678 6460 XCGAAAUAAUUCU7000AGAATTATTTGACCTGACUGAUGAG UUCAGGUCCUGAUGAGXCGAAAAUAAUUC7001GAATTATTTGACCTGAA6796461 CUUCAUCGCUGAUGAGXCGAAAUUUGGUU7002AACCAAATACGATGAAG6966462 710 6463 CUUUGCAG CUGAUGAG X CGAA AGUUUCUU 7003 AAGAAACT A CTGCAAAG 730 6464 AUCAUUUC CUGAUGAG X CGAA AUCUCGUC 7004 GACGAGAT T GAAATGAT 739 6465 UCCGUCAU CUGAUGAG X CGAA AUCAUUUC 7005 GAAATGAT C ATGACGGA 751 6466 GCCCUUUC CUGAUGAG X CGAA AGGUCCGU 7006 ACGGACCT T GAAAGGGC 782 6467 CUCUCUCU CUGAUGAG X CGAA AGCCACCU 7007 AGGIGGCT C AGAGAGAG 801 6467 GUUCCCCU CUGAUGAG X CGAA AGGUCUCC 7008 GGAGACCT T AAGGGAAC 802 6469 UGUUCCCU CUGAUGAG X CGAA AAGGUCUC 7009 GAGACCTT A AGGGAACA 814 6470 GCCGAUGA CUGAUGAG X CGAA AGCUGUUC 7010 GAACAGCT C TCATCGGC 816 6471 UGGCCGAU CUGAUGAG X CGAA AGAGCUGU 7011 ACAGCTCT C ATCGGCCA 819 6472 GAUUGGCC CUGAUGAG X CGAA AUGAGAGC 7012 GCTCTCAT C GGCCAATC 827 6473 GAGGGAGU CUGAUGAG X CGAA AUUGGCCG 7013 CGGCCAAT C ACTCCCTC 831 6474 GCUGGAGG CUGAUGAG X CGAA AGUGAUUG 7014 CAATCACT C CCTCCAGC 835 6475 GCCAGCUG CUGAUGAG X CGAA AGGGAGUG 7015 CACTCCCT C CAGCTGGC 846 6476 GGAUCUGU CUGAUGAG X CGAA AGGCCAGC 7016 GCTGGCCT C ACAGATCC 853 6477 GCCUUCUG CUGAUGAG X CGAA AUCUGUGA 7017 TCACAGAT C CAGAAGGC 883 6478 AGCACCUC CUGAUGAG X CGAA AUGGCCUG 7018 CAGGCCAT A GAGGTGCT 900 6479 CUAGGCUG CUGAUGAG X CGAA AGCGGGUC 7019 GACCCGCT C CAGCCTAG 907 6480 UCAACUUC CUGAUGAG X CGAA AGGCUGGA 7020 TCCAGCCT A GAAGTTGA Table VII. Hammert, ibozymes to CDP GCCAACUCCUGAUGAGXCGAAACUUCUAG7021CTAGAAGTTGAGTTGGC9136481 918 6482 XCGAAACUCAACU7022AGTTGAGTTCGCCGCCACUGAUGAG AGCUGUGCCUGAUGAGXCGAAAUCUCCCG7023CGGGAGATCGCACAGCT9406483 CUGGCCUGCUGAUGAGXCGAAAGUCUCUG7024CAGAGACTCCAGGCCAG9706484 AGCUUGGUCUGAUGAGXCGAAAGGCUGGC7025GCCAGCCTCACCAAGCT9826485 GCUGGCCGCUGAUGAGXCGAAAUUCUCCC7026GGGAGAATTCGGCCAGC10016486 GGCUGGCCCUGAUGAGXCGAAAAUUCUCC7027GGAGAATTCGGCCAGCC10026487 AGCUGAGACUGAUGAGXCGAAAUCUGGCU7028AGCCAGATCTCACAGCT10156488 CAAGCUGUCUGAUGAGXCGAAAGAUCUGG7029CCAGATCTCACAGCTTG10176489 UGCUGCUCCUGAUGAGXCGAAAGCUGUGA7030TCACAGCTTGAGCAGCA10246490 AGUUGUUUCUGAUGAGXCGAAAGUGUGCU7031AGCACACTCAAACAACT10576491 1078 6492 UGGCCUUU CUGAUGAG X CGAA AGUUUUUC 7032 GAAAAACT C AAAGGCCA CCUCUUCACUGAUGAGXCGAAAGUCAGCC7033GGCTGACTATGAAGAGG10956493 GACUUCAGCUGAUGAGXCGAAAUGUUCAG7034CTGAACATTCTGAAGTC11236494 GGACUUCACUGAUGAGXCGAAAAUGUUCA7035TGAACATTCTGAAGTCC11246495 ACUCCAUGCUGAUGAGXCGAAACUUCAGA7036TCTGAAGTCCATGGAGT11316496 ACGGUGCACUGAUGAGXCGAAACUCCAUG7037CATGGAGTTTGCACCGT11406497 GACGGUGCCUGAUGAGXCGAAAACUCCAU7038ATGGAGTTTGCACCGTC11416498 CGCCCUCGCUGAUGAGXCGAAACGGUGCA7039TGCACCGTCCGAGGGCG11496499 UCUCCAGCCUGAUGAGXCGAAACAGCACC7040GGTGCTGTTGCTGGAGA11976500 ACUGCAGCCUGAUGAGXCGAAAGCGGUUC7041GAACCGCTCGCTGCAGT12156501 CGUUCUCGCUGAUGAGXCGAAACUGCAGC7042GCTGCAGTCCGAGAACG12246502 CUGUUGGACUGAUGAGXCGAAAUGCGCAG7043CTGCGCATCTCCAACAG12466503 CGCUGUUGCUGAUGAGXCGAAAGAUGCGC7044GCGCATCTCCAACAGCG12486504 UCCUGGCUCUGAUGAGXCGAAACCCGCUC7045GAGCGGGTCAGCCAGGA12696505 CGGGCGCCCUGAUGAGXCGAAACUUUCAG7046CTGAAAGTCGGCGCCCG13046506 CCGGCAAACUGAUGAGXCGAAAUCCCGGG7047CCCGGGATCTTTGCCGG13176507 GGCCGGCACUGAUGAGXCGAAAGAUCCCG7048CGGGATCTTTGCCGGCC13196508 GGGCCGGCCUGAUGAGXCGAAAAGAUCCC7049GGGATCTTTGCCGGCCC13206509 1334 6510 CUGAGAAG CUGAUGAG X CGAA AGGGGGGG 7050 CCCCCCCT C CTTCTCAG CAACUGAGCUGAUGAGXCGAAAGGAGGGG7051CCCCTCCTTCTCAGTTG13376511 1338 6512 GCAACUGA CUGAUGAG X CGAA AAGGAGGG 7052 CCCTCCTT C TCAGTTGC GGGCAACUCUGAUGAGXCGAAAGAAGGAG7053CTCCTTCTCAGTTGCCC13406513 UGCGGGGCCUGAUGAGXCGAAACUGAGAA7054TTCTCAGTTGCCCCGCA13446514 AGUAUUGGCUGAUGAGXCGAAAGCCUGCU7055AGCAGGCTTCCAATACT13706515 UAGUAUUGCUGAUGAGXCGAAAAGCCUGC7056GCAGGCTTCCAATACTA13716516 ACCAUUAGCUGAUGAGXCGAAAUUGGAAG7057CTTCCAATACTAATGGT13766517 UGUACCAUCUGAUGAGXCGAAAGUAUUGG7058CCAATACTAATGGTACA13796518 CUGGUGUGCUGAUGAGXCGAAACCAUUAG7059CTAATGGTACACACCAG13856519 CUGGUGAGCUGAUGAGXCGAAACUGGUGU7060ACACCAGTTCTCACCAG13956520 GCUGGUGACUGAUGAGXCGAAAACUGGUG7061CACCAGTTCTCACCAGC13966521 CCGCUGGUCUGAUGAGXCGAAAGAACUGG7062CCAGTTCTCACCAGCGG13986522 CUUGACUUCUGAUGAGXCGAAACCCCGCU7063AGCGGGGTTAAGTCAAG14106523 UCUUGACUCUGAUGAGXCGAAAACCCCGC7064GCGGGGTTAAGTCAAGA14116524 AAAGUCUUCUGAUGAGXCGAAACUUAACC7065GGTTAAGTCAAGACTTT14156525 AGCUGAAACUGAUGAGXCGAAAGUCUUGA7066TCAAGACTTTTTCAGCT14226526 GAGCUGAACUGAUGAGXCGAAAAGUCUUG7067CAAGACTTTTTCAGCTC14236527 Table VII. Hammerh, Cbozymes to CDP UGAGCUGACUGAUGAGXCGAAAAAGUCUU7068AAGACTTTTTCAGCTCA14246528 AUGAGCUGCUGAUGAGXCGAAAAAAGUCU7069AGACTTTTTCAGCTCAT14256529 GAUGAGCUCUGAUGAGXCGAAAAAAAGUC7070GACTTTTTCAGCTCATC14266530 CCAGGGAUCUGAUGAGXCGAAAGCUGAAA7071TTTCAGCTCATCCCTGG14316531 UUGCCAGGCUGAUGAGXCGAAAUGAGCUG7072CAGCTCATCCCTGGCAA14346532 GCCAGGGGCUGAUGAGXCGAAAGGCUGGG7073CCCAGCCTACCCCTGGC14536533 UCCUGUAGCUGAUGAGXCGAAAGCCAGGG7074CCCTGGCTTCTACAGGA14636534 UUCCUGUACUGAUGAGXCGAAAAGCCAGG7075CCTGGCTTCTACAGGAA14646535 UUUUCCUGCUGAUGAGXCGAAAGAAGCCA7076TGGCTTCTACAGGAAAA14666536 UUAGUGCACUGAUGAGXCGAAAUUUUCCU7077AGGAAAATTTGCACTAA14766537 1477 6538 UUUAGUGC CUGAUGAG X CGAA AAUUUUCC 7078 GGAAAATT T GCACTAAA 1483 6539 AGAGAGUU CUGAUGAG X CGAA AGUGCAAA 7079 TTTGCACT A AACTCTCT 1488 6540 GGAGAAGA CUGAUGAG X CGAA AGUUUAGJ 7080 ACTAAACT C TCTTCTCC 1490 6541 XCGAACUGAUGAG AGAGUUUA CTTCTCCAGTAAACTCT CGCUGGAGCUGAUGAGXCGAAAGAGAGUU7082AACTCTCTTCTCCAGCG14926542 CCGCUGGACUGAUGAGXCGAAAAGAGAGU7083ACTCTCTTCTCCAGCGG19436543 UGCCGCUGCUGAUGAGXCGAAAGAAGAGA7084TCTCTTCTCCAGCGGCA14956544 1507 6545 GACUGCAU CUGAUGAG X CGAA AGCUGCCG 7085 CGGCAGCT A ATGCAGTC 1515 6546 AGUAGAAG CUGAUGAG X CGAA ACUGCAUU 7086 AATGCAGT C CTTCTACT 1518 6547 UGGAGUAG CUGAUGAG X CGAA AGGACUGC 7087 GCAGTCCT T CTACTCCA 1519 6548 UUGGAGUA CUGAUGAG X CGAA AAGGACUG 7088 CAGTCCTT C TACTCCAA 1521 6549 CCUUGGAG CUGAUGAG X CGAA AGAAGGAC 7089 GTCCTTCT A CTCCAAGG 1524 6550 UAGCCUUG CUGAUGAG X CGAA AGUAGAAG 7090 CTTCTACT C CAAGGCTA 1532 6551 UUCCUGCA CUGAUGAG X CGAA AGCCUUGG 7091 CCAAGGCT A TGCAGGAA 1561 6552 GUUGAAAA CUGAUGAG X CGAA AUCAUGCU 7092 AGCATGAT T TTTTCAAC 1562 6553 UGUUGAAA CUGAUGAG X CGAA AAUCAUGC 7093 GCATGATT T TTTCAACA 1563 6554 CUGUUGAA CUGAUGAG X CGAA AAAUCAUG 7094 CATGATTT T TTCAACAG 1654 6555 CCUGUUGA CUGAUGAG X CGAA AAAAUCAU 7095 ATGATTTT T TCAACAGG 1565 6556 ACCUGUUG CUGAUGAG X CGAA AAAAAUCA 7096 TGATTTTT T CAACAGGT 1566 6557 GACCUGUU CUGAUGAG X CGAA AAAAAAUC 7097 GATTTTTT C AACAGGTC 1574 6558 GCUGUAUG CUGAUGAG X CGAA ACCUGUUG 7098 CAACAGGT C CATACAGC 1578 6559 UUGUGCUG CUGAUGAG X CGAA AUGGACCU 7099 AGGTCCAT A CAGCACAA 1590 6560 AAGAUAUG CUGAUGAG X CGAA AGUUUGUG 7100 CACAAACT C CATATCTT 1594 6561 UGGGAAGA CUGAUGAG X CGAA AUGGAGUU 7101 AACTCCAT A TCTTCCCA 1596 6562 UUUGGGAA CUGAUGAG X CGAA AUAUGGAG 7102 CTCCATAT C TTCCCAAA 1598 6563 ACUUUGGG CUGAUGAG X CGAA AGAUAUGG 7103 CCATATCT T CCCAAAGT 1599 6564 GACUUUGG CUGAUGAG X CGAA AAGAUAUG 7104 CATATCTT C CCAAAGTC 1607 6565 UUGUAAUG CUGAUGAG X CGAA ACUUUGGG 7105 CCCAAAGT C CATTACAA 1611 6566 UUUGUUGU CUGAUGAG X CGAA AUGGACUU 7106 AAGTCCAT T ACAACAAA 1612 6567 CUUUGUUG CUGAUGAG X CGAA AAUGGACU 7107 AGTCCATT A CAACAAAG 1630 6568 AUGCCAUU CUGAUGAG X CGAA ACAUCUGG 7108 CCAGATGT C AATGGCAT 1647 6569 GGCUGGGG CUGAUGAG X CGAA AUGGGGCC 7109 GGCCCCAT C CCCCAGCC 1659 6570 CACUUUCU CUGAUGAG X CGAA ACUGGCUG 7110 CAGCCAGT C AGAAAGTG 1678 6571 CCCUCGGA CUGAUGAG X CGAA ACGCUCCC 7111 GGGAGCGT C TCCGAGGG 1680 6572 CUCCCUCG CUGAUGAG X CGAA AGACGCUC 7112 GAGCGTCT C CGAGGGAG 1711 6573 UGCCGGGC CUGAUGAG X CGAA AUUUCUGC 7113 GCAGAAAT C GCCCGGCA 1738 6574 UUGUGCUU CUGAUGAG X CGAA AUCAGCUG 7114 CAGCTGAT T AAGCACAA Table VII. Hammerh tibozymes to CDP 1739 6575 AUUGUGCU CUGAUGAG X CGAA AAUCAGCU 7115 AGCTGATT A AGCACAAT 1748 6576 UUGUCCGA CUGAUGAG X CGAA AUUGUGCU 7116 AGCACAAT A TCGGACAA CGUUGUCCCUGAUGAGXCGAAAUAUUGUG7117CACAATATCGGACAACG17506577 1760 6578 XCGAAACGUUCUG7118GACAACGTATTTTCGGACUGAUGAG 1762 6579 XCGAAAUACGUUG7119CAACGTATTTTCGGACACUGAUGAG 1763 6580 AUGUCCGA CUGAUGAG X CGAA AAUACGUU 7120 AACGTATT T TCGGACAT 1764 6581 AAUGUCCG CUGAUGAG X CGAA AAAUACGU 7121 ACGTATTT T CGGACATT UAAUGUCCCUGAUGAGXCGAAAAAAUACG7122CGTATTTTCGGACATTA17656582 CAACACAUCUGAUGAGXCGAAAUGUCCGA7123TCGGACATTATGTGTTG17726583 CCAACACACUGAUGAGXCGAAAAUGUCCG7124CGGACATTATGTGTTGG17736584 ACAGUCCCCUGAUGAGXCGAAACACAUAA7125TTATGTGTTGGGACTGT17796585 ACCCUUGACUGAUGAGXCGAAACAGUCCC7126GGGACTGTCTCAAGGGT17886586 GGACCCUUCUGAUGAGXCGAAAGACAGUC7127GACTGTCTCAAGGGTCC17906587 1797 6588 CGCUCACG CUGAUGAG X CGAA ACCCUUGA 7128 TCAAGGGT C CGTGAGCG 1810 6589 CGGGCCAG CUGAUGAG X CGAA AUCUCGCU 7129 AGCGAGAT T CTGGCCCG 1811 6590 CCGGGCCA CUGAUGAG X CGAA AAUCUCGC 7130 GCGAGATT C TGGCCCGG 1835 6591 AGUCAGUU CUGAUGAG X CGAA AUUCCAUG 7131 CATGGAAT A AACTGACT 1846 6592 UUGCCACG CUGAUGAG X CGAA ACAGUCAG 7132 CTGACTGT T CGTGGCAA 1847 6593 CUUGCCAC CUGAUGAG X CGAA AACAGUCA 7133 TGACTGTT GTGGCAAG 1863 6594 UCUUGUGA CUGAUGAG X CGAA AUGGCUCC 7134 GGAGCCAT T TCACAAGA AUCUUGUGCUGAUGAGXCGAAAAUGGCUC7135GAGCCATTTCACAAGAT18646595 1865 6596 CAUCUUGU CUGAUGAG X CGAA AAAUGGCU 7136 AGCCATTT C ACAAGATG CGGAGAGGCUGAUGAGXCGAAACUGUUUC7137GAAACAGTTCCTCTCCG18816597 1882 6598 UCGGAGAG CUGAUGAG X CGAA AACUGUUU 7138 AAACAGTT C CTCTCCGA 1885 6599 UCAUCGGA CUGAUGAG X CGAA AGGAACUG 7139 CAGTTCCT C TCCGATGA 1887 6600 GCUCAUCG CUGAUGAG X CGAA AGAGGAAC 7140 GTTCCTCT C CGATGAGC 1903 6601 AGGGCCAG CUGAUGAG X CGAA AUGUUCUG 7141 CAGAACAT C CTGGCCCT 1912 6602 AUGCUACG CUGAUGAG X CGAA AGGGCCAG 7142 CTGGCCCT C CGTAGCAT 1916 6603 UUGGAUGC CUGAUGAG X CGAA ACGGAGGG 7143 CCCTCCGT A GCATCCAA 1921 6604 CUGCCUUG CUGAUGAG X CGAA AUGCUACG 7144 CGTAGCAT C CAAGGCAG 1943 6605 CUGGCCUG CUGAUGAG X CGAA AUUCUCUC 7145 GAGAGAAT C CAGGCCAG 1966 6606 UCCUGAAA CUGAUGAG X CGAA AGUCUGUU 7146 AACAGACT A TTTCAGGA 1968 6607 CUUCCUGA CUGAUGAG X CGAA AUAGUCUG 7147 CAGACTAT T TCAGGAAG 1969 6608 ACUUCCUG CUGAUGAG X CGAA AAUAGUCU 7148 AGACTATT T CAGGAAGT UACUUCCUCUGAUGAGXCGAAAAAUAGUC7149GACTATTTCAGGAAGTA19706609 CGUUUCGGCUGAUGAGXCGAAACUUCCUG7150CAGGAAGTACCGAAACG19786610 UACCUUCACUGAUGAGXCGAAACCCAUUU7151AAATGGGTCTGAAGGTA19986611 GGUGAUGUCUGAUGAGXCGAAACCUUCAG7152CTGAAGGTAACATCACC20066612 CGGGUGGUCUGAUGAGXCGAAAUGUUACC7153GGTAACATCACCACCCG20116613 GAGGCUCGCUGAUGAGXCGAAAUCCGGGU7154ACCCGGATCCGAGCCTC20236614 2031 6615 CAGUCUCC CUGAUGAG X CGAA AGGCUCGG 7155 CCGAGCCT C GGAGACTG CUUCAUCACUGAUGAGXCGAAAGCCAGUC7156GACTGGCTCTGATGAAG20436616 2056 6617 AUGGACUU CUGAUGAG X CGAA AUGGCUUC 7157 GAAGCCAT C AAGTCCAT 2061 6618 CUAGGAUG CUGAUGAG X CGAA ACUUGAUG 7158 CATCAAGT C CATCCTAG 2065 6619 UGCUCUAG CUGAUGAG X CGAA AUGGACUU 7159 AAGTCCAT C CTAGAGCA 2068 6620 GCUUGCUC CUGAUGAG X CGAA AGGAUGGA 7160 TCCATCCT A GAGCAAGC 2089 6621 UGCACUUG CUGAUGAG X CGAA AGCUCCCU 7161 AGGGAGCT C CAAGTGCA Table VII. Hammerh. Gbozymes to CDP UGCGGAGGCUGAUGAGXCGAAAGGCUGGG7162CCCAGCCTTCCTCCGCA21236622 2124 6623 AUGCGGAG CUGAUGAG X CGAA AAGGCUGG 7163 CCAGCCTT C CTCCGCAT CGGAUGCGCUGAUGAGXCGAAAGGAAGGC7164GCCTTCCTCCGCATCCG21276624 2133 6625 CGCUGCCGCUGAUGAG X 7165CTCCGCATCCGGCAGCGAUGCGGAG GCUCAUCACUGAUGAGXCGAAAGUUCCCG7166CGGGAACTCTGATGAGC21486626 AUGGAGCGCUGAUGAGXCGAAAUGGGCUC7167GAGCCCATCCGCTCCAT21616627 GCAGGAUGCUGAUGAGXCGAAAGCGGAUG7168CATCCGCTCCATCCTGC21666628 2170 6629 UGCUGCAG CUGAUGAG X CGAA AUGGAGCG 7169 CGCTCCAT C CTGCAGCA 2215 6630 GCAGGGUC CUGAUGAG X CGAA AGGGCAGC 7170 GCTGCCCT C GACCCTGC CCUGCUUUCUGAUGAGXCGAAAGGCAGGG7171CCCTGCCTTAAAGCAGG22266631 2227 6632 GCCUGCUU CUGAUGAG X CGAA AAGGCAGG 7172 CCTGCCTT A AAGCAGGC CACUCUGGCUGAUGAGXCGAAACAGUGGU7173ACCACTGTCCCAGAGTG22446633 2257 6634 AGGAUGGU CUGAUGAG X CGAA AUGUCACU 7174 AGTGACAT C ACCATCCT 2263 6635 GGGGUGAG CUGAUGAG X CGAA AUGGUGAU 7175 ATCACCAT C CTCACCCC UUGGGGGUCUGAUGAGXCGAAAGGAUGGU7176ACCATCCTCACCCCCAA22666636 2278 6637 GUGGACAG CUGAUGAG X CGAA AGCUUGGG 7177 CCCAAGCT T CTGTCCAC 2279 6638 GGUGGACA CUGAUGAG X CGAA AAGCUUGG 7178 CCAAGCTT C TGTCCACC GCGAGGUGCUGAUGAGXCGAAACAGAAGG7179GCTTCTGTCCACCTCGC22836639 2289 6640 GCAUGGGC CUGAUGAG X CGAA AGGUGGAC 7180 GTCCACCT C GCCCATGC 2307 6641 GGUAGCUG CUGAUGAG X CGAA ACACGGUG 7181 CACCGTGT C CAGCTACC 2313 6642 GAGGUGGG CUGAUGAG X CGAA AGCUGGAC 7182 GTCCAGCT A CCCACCTC GAUGGCGACUGAUGAGXCGAAAGGUGGGU7183ACCCACCTCTCGCCATC23216643 2323 6644 GAGAUGGC CUGAUGAG X CGAA AGAGGUGG 7184 CCACCTCT C GCCATCTC 2329 6645 UUCAGGGA CUGAUGAG X CGAA AUGGCGAG 7185 CTCGCCAT C TCCCTGAA 2331 6646 UCUUCAGG CUGAUGAG X CGAA AGAUGGCG 7186 CGCCATCT C CCTGAAGA 2346 6647 GAGCUGCG CUGAUGAG X CGAA AGGGCUUC 7187 GAAGCCCT C CGCAGCTC 2354 6648 GGCCUCAG CUGAUGAG X CGAA AGCUGCGG 7188 CCGCAGCT C CTGAGGCC 2370 6649 XCGAAAGGCACCG7189CGGTGCCTCTGCTCTGCCUGAUGAG 2375 6650 GUUCGGCA CUGAUGAG X CGAA AGCAGAGG 7190 CCTCTGCT C TGCCGAAC 2395 6651 UCCUUUUU CUGAUGAG X CGAA AGGGCCGG 7191 CCGGCCCT C AAAAAGGA 2447 6652 UUGUGCAC CUGAUGAG X CGAA AUCGGCUG 7192 CAGCCGAT T GTGCACAA 2461 6653 UGUCUCAG CUGAUGAG X CGAA ACCCCUUG 7193 CAAGGGGT C CTGAGACA 2553 6654 CCUCGGAG CUGAUGAG X CGAA AGGCGGCA 7194 TGCCGCCT C CTCCGAGG 2556 6655 CCUCCUCG CUGAUGAG X CGAA AGGAGGCG 7195 CGCCTCCT C CGAGGAGG CUCGGCCCCUGAUGAGXCGAAAGGCUGGC7196GCCAGCCTCGGGCCGAG26336656 CUGGAGCUCUGAUGAGXCGAAACUGCGCU7197AGCGCAGTCAGCTCCAG26486657 GGUCCCUGCUGAUGAGXCGAAAGCUGACU7198AGTCAGCTCCAGGGACC26536658 CUGACGACCUGAUGAGXCGAAAGGGUCCC7199GGGACCCTCGTCGTCAG26646659 2667 6660 ACUCUGAC CUGAUGAG X CGAA ACGAGGGU 7200 ACCCTCGT C GTCAGAGT 2670 6661 AGUACUCU CUGAUGAG X CGAA ACGACGAG 7201 CTCGTCGT C AGAGTACT 2676 6662 CCUUCCAG CUGAUGAG X CGAA ACUCUGAC 7202 GTCAGAGT A CTGGAAGG 2703 6663 AGUAUGGG CUGAUGAG X CGGA ACUCAGCG 7203 CGCTGAGT C CCCATACT 2709 6664 UCUGGGAG CUGAUGAG X CGAA AUGGGGAC 7204 GTCCCCAT A CTCCCAGA 2712 6665 AGCUCUGG CUGAUGAG X CGAA AGUAUGGG 7205 CCCATACT C CCAGAGCT 2721 6666 UCAGCUCU CUGAUGAG X CGAA AGCUCUGG 7206 CCAGAGCT C AGAGCTGA 2732 6667 CCCGGUCA CUGAUGAG X CGAA ACUCAGCU 7207 AGCTGAGT C TGACCGGG 2781 6668 UCGGGGAG CUGAUGAG X CGAA AUGGCAGG 7208 CCTGCCAT C CTCCCCGA Table VII. Hammerh.. tibozymes to CDP CGAUCGGGCUGAUGAGXCGAAAGGAUGGC7209GCCATCCTCCCCGATCG27846669 AUGGGCACCUGAUGAGXCGAAAUCGGGGA7210TCCCCGATCGTGCCCAT27916670 UGGGCUUGCUGAUGAGXCGAAACAUGGGC7211GCCCATGTCCAAGCCCA28026671 GGGGGACCCUGAUGAGXCGAAAGGGCUUG7212CAAGCCCTCGGTCCCCC28206672 AGCGGGGGCUGAUGAGXCGAAACCGAGGG7213CCCTCGGTCCCCCCGCT28246673 AGACCUCGCUGAUGAGXCGAAACUGCUCG7214CGAGCAGTACGAGGTCT28476674 UACAUGUACUGAUGAGXCGAAACCUCCUA7215TACGAGGTCTACATGTA28546675 GGUACAUGCUGAUGAGCCGAAAGACCUCG7216CGAGGTCTACATGTACC28566676 CCUCCUGGCUGAUGAGXCGAAACAUGUAG7217CTACATGTACCAGGAGG28626677 GUGAGCUCCUGAUGAGXCGAAAUGGUGUC7218GACACCATCGAGCTCAC28816678 UGCCGGGUCUGAUGAGXCGAAAGCUCGAU7219ATCGAGCTCACCCGGCA28876679 2899 6680 XCGAAACCUGCCG7220CGGCAGGTTAAGGAAAACUGAUGAG 2900 6681 XCGAAAACCUGCC7221GGCAGGTTAAGGAAAAGCUGAUGAG CUCUGGCACUGAUGAGXCGAAAUGCCGUU7222AACGGCATCTGCCAGAG29266682 2938 6683 UCCCCGAA CUGAUGAG X CGAA AUUCUCUG 7223 CAGACAAT C TTCGGGGA 2940 6684 UCUCCCCG CUGAUGAG X CGAA AGAUUCUC 7224 GAGAATCT T CGGGGAGA 2941 6685 UUCUCCCC CUGAUGAG X CGAA AAGAUUCU 7225 AGAATCTT C GGGGAGAA 2964 6686 UGCCCUGG CUGAUGAG X CGAA ACAGGCCC 7226 GGGCCTGT C CCAGGGCA 2977 6687 AUGUCGCU CUGAUGAG X CGAA ACGCUGCC 7227 GGCAGCGT C AGCGACAT UCGGUCGGCUGAUGAGXCGAAACAGCAUG7228CATGCTGTCCCGACCGA29916688 3039 6689 UCCGGAUG CUGAUGAG X CGAA AGGGUUCU 7229 AGAACCCT T CATCCGGA 3040 6690 AUCCGGAU CUGAUGAG X CGAA AAGGGUUC 7230 GAACCCTT C ATCCGGAT 3043 6691 UGCAUCCG CUGAUGAG X CGAA AUGAAGGG 7231 CCCTTCAT C CGGATGCA 3055 6692 UUCAGCCA CUGAUGAG X CGAA AGCUGCAU 7232 ATGCAGCT C TGGCTGAA 3073 6693 CCCUGGCC CUGAUGAG X CGAA AGCUCGCC 7233 GGCGAGCT A GGCCAGGG 3085 6694 ACGGGUAG CUGAUGAG X CGAA ACACCCUG 7234 CAGGGTGT T CTACCCGT 3086 6695 GACGGGUA CUGAUGAG X CGAA AACACCCU 7235 AGGGTGTT C TACCCGTC 3088 6696 XCGAAAGAACACC7236GGTGTTCTACCCGTCCACUGAUGAG UGGCCCUGCUGAUGAGXCGAAACGGGUAG7237CTACCCGTCCAGGGCCA30946697 3118 6698 GAGUGGAG CUGAUGAG X CGAA ACUGGCCC 7238 GGGCCAGT C CTCCACTC 3121 6699 ACGGAGUG CUGAUGAG X CGAA AGCACUGG 7239 CCAGTCCT C CACTCCGT 3126 6700 AUGUCACG CUGAUGAG X CGAA AGUGGAGG 7240 CCTCCACT C CGTGACAT 3135 6701 CCUGGAGC CUGAUGAG X CGAA AUGUCACG 7241 CTGGACAT C GCTCCAGG 3139 6702 GGGUCCUG CUGAUGAG X CGAA AGCGAUGU 7242 ACATCGCT C CAGGACCC 3171 6703 UGCUUUCU CUGAUGAG X CGAA AGCUCACA 7243 TGTGAGCT C AGAAAGCA 3182 6704 GGUCUUUG CUGAUGAG X CGAA AGUGCUUU 7244 AAAGCACT C CAAAGACC 3192 6705 AGCUGGCG CUGAUGAG X CGAA AGGUCUUU 7245 AAAGACCT C CGCCAGCT 3219 6706 UCAUCGGG CUGAUGAG X CGAA ACUCAGGG 7246 CCCTGAGT C CCCGATGA 3230 6707 CUCACUGG CUGAUGAG X CGAA ACUCAUCG 7247 CGATGAGT T CCAGTGAG 3231 6708 ACUCACUG CUGAUGAG X CGAA AACUCAUC 7248 GATGAGTT C CAGTGAGT 3240 6709 UCUUCACC CUGAUGAG X CGAA ACUCACUG 7249 CAGTGAGT C GGTGAAGA 3265 6710 GGCUGCUG CUGAUGAG X CGAA ACCAGCUC 7250 GAGCTGGT C CAGCAGCC 3278 6711 GAUGGGGG CUGAUGAG X CGAA ACAGGGCU 7251 AGCCCTGT C CCCCCATC 3286 6712 CUCGCCUC CUGAUGAG X CGAA AUGGGGGG 7252 CCCCCCAT C GAGGCGAG 3336 6713 GGGAGUCG CUGAUGAG X CGAA AUGCUGGC 7253 GCCAGCAT C CGACTCCC 3342 6714 UGGGCUGG CUGAUGAG X CGAA AGUCGGAU 7254 ATCCGACT C CCAGCCCA 3365 6715 UCCGGAGA CUGAUGAG X CGAA AGGCAGCG 7255 CGCTGCCT C TCTCCGGA Table VII. Hammerh. wibozymes to CDP UGUCCGGACUGAUGAGXCGAAAGAGGCAG7256CTGCCTCTCTCCGGACA33876761 3369 6717 XCGAAAGAGAGGC7257GCCTCTCTCCGGACACTCUGAUGAG UGAGGGCCCUGAUGAGXCGAAAGUGUCCG7258CGGACACTCGGCCCTCA33786718 UGGAUGCUCUGAUGAGXCGAAAGGGCCGA7259TCGGCCCTCAGCATCCA33856719 AAUUCUUGCUGAUGAGXCGAAAUGCUGAG7260CTCAGCATCCAAGAATT33916720 UGGCUACUCUGAUGAGXCGAAAUUCUUGG7261CCAAGAATTAGTAGCCA33996721 AUGGCUACCUGAUGAGXCGAAAAUUCUUG7262CAAGAATTAGTAGCCAT34006722 GACAUGGCCUGAUGAGXCGAAACUAAUUC7263GAATTAGTAGCCATGTC34036723 GCUCCGGGCUGAUGAGXCGAAACAUGGCU7264AGCCATGTCCCCGGAGC34116724 UUAUGCCGCUGAUGAGXCGAAAGGUGUCC7265GGACACCTACGGCATAA34296725 CGCUUGGUCUGAUGAGXCGAAAUGCCGUA7266TACGGCATAACCAAGCG34366726 3475 6727 CGCUGGCC CUGAUGAG X CGAA AGGUUGUU 7267 AACAACCT A GGCCAGCG 3486 6728 CCCCAAAU CUGAUGAG X CGAA AGCGCUGG 7268 CCAGCGCT T ATTTGGGG 3487 6729 UCCCCAAA CUGAUGAG X CGAA AAGCGCUG 7269 CAGCGCTT A TTTGGGGA UCUCCCCACUGAUGAGXCGAAAUAAGCGC7270GCTCTTATTTGGGGAGA34896730 GUCUCCCCCUGAUGAGXCGAAAAUAAGCG7271CGCTTATTTGGGGAGAC34906731 AGCCCUAACUGAUGAGXCGAAAUGGUCUC7272GAGACCATCTTAGGGCT35026732 UGAGCCCUCUGAUGAGXCGAAAGAUGGUC7273GACCATCTTAGGGCTCA35046733 GUGAGCCCCUGAUGAGXCGAAAAGAUGGU7274ACCATCTTAGGGCTCAC35056734 3511 6735 CCUUGGGU CUGAUGAG X CGAA AGCCCUAA 7275 TTAGGGCT C ACCCAAGG 3522 6736 CAGAGACA CUGAUGAG X CGAA AGCCUUGG 7276 CCAAGGCT C TGTCTCTG 3326 6737 AGGUCAGA CUGAUGAG X CGAA ACAGAGCC 7277 GGCTCTGT C TCTGACCT 3528 6738 GGAGGUCA CUGAUGAG X CGAA AGACAGAG 7278 CTCTGTCT C TGACCTCC 3535 6739 CGGGCAAG CUGAUGAG X CGAA AGGUCAGA 7279 TCTGACCT C CTTGCCCG 3538 6740 GGGCGGGC CUGAUGAG X CGAA AGGAGGUC 7280 GACCTCCT T GCCCGCCC 3560 6741 ACUGAGCU CUGAUGAG X CGAA AUGCCAGG 7281 CCTGGCAT A AGCTCAGT 3565 6742 UUCAGACU CUGAUGAG X CGAA AGCUUAUG 7282 CATAAGCT C AGTCTGAA 3569 6743 UCCUUUCA CUGAUGAG X CGAA ACUGAGCU 7283 AGCTCAGT C TGAAAGGA 3388 6744 UCCGGACG CUGAUGAG X CGAA AGGGCUCU 7284 AGAGCCCT T CTTCCGGA 3589 6745 AUCCGGAC CUGAUGAG X CGAA AAGGGCUC 7285 GAGCCCTT C GTCCGGAT 3592 6746 UGCAUCCG CUGAUGAG X CGAA ACGAAGGG 7286 CCCTTCGT C CGGATGCA 3669 6747 GCUUCAUG CUGAUGAG X CGAA AGGCUUUC 7287 GAAAGCCT A CATGAAGC 3690 6748 CACUGACU CUGAUGAG X CGAA AGCUGUGC 7288 GCACAGCT A AGTCAGTG 3694 6749 CUGUCACU CUGAUGAG X CGAA ACUGAGCU 7289 AGCTCAGT C AGTGACAG 3723 6750 UGCCGACA CUGAUGAG X CGAA AGGGCGGU 7290 ACCGCCCT C TGTCGGCA 3727 6751 UCGGUGCC CUGAUGAG X CGAA ACAGAGGG 7291 CCCTCTGT C GGCACCGA 3738 6752 CCUGGCUG CUGAUGAG X CGAA ACUCGGUG 7292 CACCGAGT A CAGCCAGG 3800 6753 CUCCUCCG CUGAUGAG X CGAA AGCCAGCA 7293 TGCTGGCT C CGGAGGAG 3831 6754 UUUGCUGA CUGAUGAG X CGAA ACGCUCGU 7294 ACGAGCGT A TCAGCAAA 3833 6755 CUUUUGCU CUGAUGAG X CGAA AUACGCUC 7295 GAGCGTAT C AGCAAAAG 3846 6756 GUGACGGG CUGAUGAG X CGAA AUGGCUUU 7296 AAAGCCAT A CCCGTCAC 3852 6757 UUUUUGGU CUGAUGAG X CGAA ACGGGUAU 7297 ATACCCGT A ACCAAAAA 3865 6758 AGGUCUUC CUGAUGAG X CGAA AUGGUUUU 7298 AAAACCAT C GAAGACCT UGGGUGGCCUGAUGAGXCGAAAGGUCUUC7299GAAGACCTCGCCACCCA38746759 UUCAGGUUCUGAUGAGXCGAAAGCUGGGU7300ACCCAGCTCAACCTGAA38866760 CAGUUGAUCUGAUGAGXCGAAACGGUGCU7301AGCACCGTCATCAACTG39076761 3910 6762 AACCAGUU CUGAUGAG X CGAA AUGACGGU 7302 ACCGTCAT C AACTGGTT Table VII. HammerLRibozymes to CDP 3918 6763 AGUUGUGG CUGAUGAG X CGAA ACCAGUUG 7303 CAACTGGT T CCACAACT UAGUUGUGCUGAUGAGXCGAAAACCAGUU7304AACTGGTTCCACAACTA39196864 3927 6865 XCGAAAGUUGUGG7305CCACAACTACAGGTCTCCUGAUGAG 3933 6766 XCGAAACCUGUAG7306CTACAGGTCTCGGATCCCUGAUGAG 3935 6767 GCGGAUCC CUGAUGAG X CGAA AGACCUGU 7307 ACAGGTCT C GGATCCGC 3940 6768 XCGAAAUCCGAGA7308TCTCGGATCCGCAGAGACUGAUGAG CCUCAAUGCUGAUGAGXCGAAACAGUUCU7309AGAACTGTTCATTGAGG39546769 UCCUCAAUCUGAUGAGXCGAAAACAGUUC7310GAACTGTTCATTGAGGA39556770 AUUUCCUCCUGAUGAGXCGAAAUGAACAG7311CTGTTCATTGAGGAAAT39586771 CCGGCCUGCUGAUGAGXCGAAAUUUCCUC7312GAGGAAATTCAGGCCGG39676772 CCCGGCCUCUGAUGAGXCGAAAAUUUCCU7313AGGAAATTCAGGCCGGG39686773 CUGGCCCUCUGAUGAGXCGAAACUCCCGG7314CCGGGAGTCAGGGCCAG39806774 4005 6775 CCGAGGGU CUGAUGAG X CGAA AGUCGCUG 7315 CAGCGACT C ACCCTCGG UGCGGGCCCUGAUGAGXCGAAAGGGUGAG7316CTCACCCTCGGCCCGCA40116776 4041 6777 CGCCCUCC CUGAUGAG X CGAA AGCUGGGC 7317 GCCCAGCT C GGAGGGCG 4113 6778 CUCCCUGA CUGAUGAG X CGAA ACUUGGGC 7318 GCCCAAGT C TCAGGGAG 4115 6779 CUCUCCCU CUGAUGAG X CGAA AGACUUGG 7319 CCAAGTCT C AGGGAGAG 4176 6780 GGGUCCCC CUGAUGAG X CGAA AGGGCGGC 7320 GCCGCCCT C GGGGACCC 4263 6781 CGGUCGCG CUGAUGAG X CGAA AGGCGGGG 7321 CCCCGCCT C CGCGACCG 4307 6782 GGCUGAGG CUGAUGAG X CGAA AGCGGCGU 7322 ACGCCGCT A CCTCAGCC CGGCGGCUCUGAUGAGXCGAAAGGUAGCG7323CGCTACCTCAGCCGCCG43116783 4353 6784 GUGGCGCG CUGAUGAG X CGAA ACGUCGGG 7324 CCCGACGT C CGCGCCAC UCUGCAGCCUGAUGAGXCGAAAGCUGGGC7325GCCCAGCTCGCTGCAGA44076785 AGGCCGAACUGAUGAGXCGAAAGGCUCUG7326CAGAGCCTTTTCGGCCT44206786 GAGGCCGACUGAUGAGXCGAAAAGGCUCU7327AGACGGTTTTCGGCCTC44216787 GGAGGCCGCUGAUGAGXCGAAAAAGGCUC7328GAGCCTTTTCGGCCTCC44226788 GGGAGGCCCUGAUGAGXCGAAAAAAGGCU7329AGCCTTTTCGGCCTCCC44236789 GCCUCGGGCUGAUGAGXCGAAAGGCCGAA7330TTCGGCCTCCCCGAGGC44296790 UGUCGCGCCUGAUGAGXCGAAAGUCCCGG7331CCGGGACTCGCGCGACA44556791 UGCUGUUCCUGAUGAGXCGAAAGUUCGCG7332CGCGAACTTGAACAGCA44946792 4504 6793 CGGUGGAU CUGAUGAG X CGAA AUGCUGUU 7333 AACAGCAT C ATCCACCG 4507 6794 AGGCGGUG CUGAUGAG X CGAA AUGAUGCU 7334 AGCATCAT C CACCGCCT CCAUUCGACUGAUGAGXCGAAAGGUUCCU7335AGGAACCTATCGAATGG45446795 4546 6796 UCCCAUUC CUGAUGAG X CGAA AUAGGUUC 7336 GAACCTAT C GAATGGGA 4557 6797 CCCCUCAG CUGAUGAG X CGAA ACUCCCAU 7337 ATGGGAGT T CTGAGGGG 4558 6798 GCCCCUCA CUGAUGAG X CGAA AACUCCCA 7338 TGGGAGTT C TGAGGGGC 4618 6799 CCCCGUCC CUGAUGAG X CGAA ACCCCGUC 7339 GACGGGGT C GGACGGGG 4656 6800 CGCGGGCC CUGAUGAG X CGAA AGCCCAGG 7340 CCTGGGCT T GGCCCGCG 4713 6801 GGACCGUG CUGAUGAG X CGAA AGGGGGUC 7341 GACCCCCT C CACGGTCC 4720 6802 AGGCCGCG CUGAUGAG X CGAA ACCGUGGA 7342 TCCACGGT C CGCGGCCT 4750 6803 CGGCCUUG CUGAUGAG X CGAA AUCUGGGC 7343 GCCCAGAT C CAAGGCCG 4774 6804 GGGCCGCA CUGAUGAG X CGAA AGUGGGUC 7344 GACCCACT C TGCGGCCC 4801 6805 GGUUGGUG CUGAUGAG X CGAA AGGCCGCA 7345 TGCGGCCT T CACCAACC 4853 6806 AGUGCGCA CUGAUGAG X CGAA AGCGGUCC 7346 GGACCGCT T TGCGCACT 4854 6807 AAGUGCGC CUGAUGAG X CGAA AAGCGGUC 7347 GACCGCTT T GCGCACTT 4862 6808 AGGGCGGU CUGAUGAG X CGAA AGUGCGCA 7348 TGCGCACT T ACCGCCCT 4863 6809 CAGGGCGG CUGAUGAG X CGAA AAGUGCCC 7439 GCGCACTT A CCGCCCTG Table VII. Hammert. ibozymes to CDP 4889 6810 CCUAUGGC CUGAUGAG X CGAA AUUUUGCC 7350 GGCAAAAT C GCCATAGG 4895 6811 CCUUGGCC CUGAUGAG X CGAA AUGGCGAU 7351 ATCGCCAT A GGCCAAGG 4909 6812 XCGAAAUGCACCU7352AGGTGCATATAGAAAACCUGAUGAG 4911 6813 XCGAAAUAUGCAC7353GTGCATATAGAAAACAACUGAUGAG UUGGGCUUCUGAUGAGXCGAAAUGCUCCU7354AGGAGCATTAAGCCCAA49286814 4929 6815 AUUGGGCU CUGAUGAG X CGAA AAUGCUCC 7355 GGAGCATT A AGCCCAAT ACGACAUACUGAUGAGXCGAAAUUGGGCU7356AGCCCAATCTATGTCGT49386816 ACACGACACUGAUGAGXCGAAAGAUUGGG7357CCCAATCTATGTCGTGT49406817 GAAAACACCUGAUGAGXCGAAACAUAGAU7358ATCTATGTCGTGTTTTC49446818 UCCUUGAACUGAUGAGXCGAAACACGACA7359TGTCGTGTTTTCAAGGA49496819 UUCCUUGACUGAUGAGXCGAAAACACGAC7360GTCGTGTTTTCAAGGAA49506820 CUUCCUUGCUGAUGAGXCGAAAAACACGA7361TCGTGTTTTCAAGGAAG49516821 4952 6822 UCUUCCUU CUGAUGAG X CGAA AAAACACG 7362 CGTGTTTT C AAGGAAGA 4978 6823 AAAAGCUC CUGAUGAG X CGAA ACCACACA 7363 TGTGTGGT C GAGCTTTT GUACAAAACUGAUGAGXCGAAAGCUCGAC7364GTCGAGCTTTTTTGTAC49846824 4985 6825 GGUACAAA CUGAUGAG X CGAA AAGCUCGA 7365 TCGAGCTT T TTTGTACC 4986 6826 GGGUACAA CUGAUGAG X CGAA AAAGCUCG 7366 CGAGCTTT T TTGTACCC AGGGUACACUGAUGAGXCGAAAAAAGCUC7367GAGCTTTTTTGTACCCT49876827 CAGGGUACCUGAUGAGXCGAAAAAAAGCU7368AGCTTTTTTGTACCCTG49886828 4991 6829 CUUCAGGG CUGAUGAG X CGAA ACAAAAAA 7369 TTTTTTGT A CCCTGAAG 5003 6830 AUAAAAAA CUGAUGAG X CGAA ACACUUCA 7370 TGAAGTGT T TTTTTTAT 5004 6831 AAUAAAAA CUGAUGAG X CGAA AACACUUC 7371 GAAGTGTT T TTTTTATT 5005 6832 CAAUAAAA CUGAUGAG X CGAA AAACACUU 7372 AAGTGTTT T TTTTATTG 5006 6833 GCAAUAAA CUGAUGAG X CGAA AAAACACU 7373 AGTGTTTT T TTTATTGC 5007 6834 GGCAAUAA CUGAUGAG X CGAA AAAAACAC 7374 GTGTTTTT T TTATTGCC 5008 6835 GGGCAAUA CUGAUGAG X CGAA AAAAAACA 7375 TGTTTTTT T TATTGCCC 5009 6836 AGGGCAAU CUGAUGAG X CGAA AAAAAAAC 7376 GTTTTTTT T ATTGCCCT 5010 6837 UAGGGCAA CUGAUGAG X CGAA AAAAAAAA 7377 TTTTTTTT A TTGCCCTA 5012 6838 CUUAGGGC CUGAUGAG X CGAA AUAAAAAA 7378 TTTTTTAT T GCCCTAAG AAAUCACUCUGAUGAGXCGAAAGGGCAAU7379ATTGCCCTAAGTGATTT50186839 CCUGUGGACUGAUGAGXCGAAAUCACUUA7380TAAGTGATTTCCACAGG50256840 ACCUGUGGCUGAUGAGXCGAAAAUCACUU7381AAGTGATTTCCACAGGT50266841 AACCUGUGCUGAUGAGXCGAAAAAUCACU7382AGTGATTTCCACAGGTT50276842 5035 6843 UAUUCCAG CUGAUGAG X CGAA ACCUGUGG 7383 CCACAGGT T CTGGAATA 5036 6844 UUAUUCCA CUGAUGAG X CGAA AACCUGUG 7384 CACAGGTT C TGGAATAA GUAAGAGUCUGAUGAGXCGAAAUUCCAGA7385TCTGGAATAACTCTTAC50436845 5047 6846 AGCUGUAA CUGAUGAG X CGAA AGUUAUUC 7386 GAATAACT C TTACAGCT 5049 6847 AAAGCUGU CUGAUGAG X CGAA AGAGUUAU 7387 ATAACTCT A ACAGCTTT 5050 6848 CAAAGCUG CUGAUGAG X CGAA AAGAGUUA 7388 TAACTCTT A CAGCTTTG 5056 6849 ACAAGGCA CUGAUGAG X CGAA AGCUGUAA 7389 TTACAGCT T TGCCTTGT 5057 6850 CACAAGGC CUGAUGAG X CGAA AAGCUGUA 7390 TACAGCTT T GCCTTGTG 5062 6851 GAGGACAC CUGAUGAG X CGAA AGGCAAAG 7391 CTTTGCCT T GTGTCCTC 5067 6852 AACAAGAG CUGAUGAG X CGAA ACACAAGG 7392 CCTTGTGT C CTCTTGTT 5070 6853 CGGAACAA CUGAUGAG X CGAA AGGACACA 7393 TGTGTCCT C TTGTTCCG 5072 6854 CACGGAAC CUGAUGAG X CGAA AGAGGACA 7394 TGTCCTCT T GTTCCGTG 5075 6855 CCACACGG CUGAUGAG X CGAA ACAAGAGG 7395 CCTCTTGT T CCGTGTGG 5076 6856 CCCACACG CUGAUGAG X CGAA AACAAGAG 7396 CTCTTGTT C CGTGTGGG Table VII. Hammer. Ribozymes to CDP UUCUUUUACUGAUGAGXCGAAAGCCCACA7397TGTGGGCTTTAAAAGAA50876857 UUUCUUUUCUGAUGAGXCGAAAAGCCCAC7398GTGGGCTTTAAAAGAAA50886858 UUUUCUUUCUGAUGAGXCGAAAAAGCCCA7399TGGGCTTTAAAAGAAAA50896859 GUGGGUUUCUGAUGAGXCGAAAUUUUUUU7400AAAAAAATCAAACCCAC51036860 CCUUUUAACUGAUGAGXCGAAAUGUGGGU7401ACCCACATATTAAAAGG51146861 CCCCUUUUCUGAUGAGXCGAAAUAUGUGG7402CCACATATTAAAAGGGG51166862 CCCCCUUUCUGAUGAGXCGAAAAUAUGUG7403CACATATTAAAAGGGGG51176863 CAGAUAAACUGAUGAGXCGAAAGCCCCCU7404AGGGGGCTTTTTATCTG51286864 GCAGAUAACUGAUGAGXCGAAAAAGCCCC7406GGGGCTTTTTATCTGCC51296865 5130 6866 GGCAGAUA CUGAUGAG X CGAA AAAGCCCC 7406 GGGGCTTT T TATCTGCC UGGCAGAUCUGAUGAG51316867 X CGAA AAAAGCCC AATCTGCCAGGGCTTTT 5132 6868 AUGGCAGA CUGAUGAG X CGAA AAAAAGCC 7408 GGCTTTTT A TCTGCCAT 5134 6869 AGAUGGCA CUGAUGAG X CGAA AUAAAAAG 7409 CTTTTTAT C TGCCATCT 5141 6870 AGCCAUUA CUGAUGAG X CGAA AUGGCAGA 7410 TCTGCCAT C TAATGGCT 5143 6871 GAAGCCAU CUGAUGAG X CGAA AGAUGGCA 7411 TGCCATCT A ATGGCTTC 5150 6872 UCGCUCUG CUGAUGAG X CGAA AGCCAUUA 7412 TAATGGCT T CAGAGCGA 5151 6873 AUCGCUCU CUGAUGAG X CGAA AAGCCAUU 7413 AATGGCTT C AGAGCGAT 5160 6874 UAGUGUAU CUGAUGAG X CGAA AUCGCUCU 7414 AGAGCGAT A ATACACTA 5163 6875 UAAUAGUG CUGAUGAG X CGAA AUUAUCGC 7415 GCGATAAT A CACTATTA 5168 6876 GAAGAUAA CUGAUGAG X CGAA AGUGUAUU 7416 AATACACT A TTATCTTC 5170 6877 AAGAAGAU CUGAUGAG X CGAA AUAGUGUA 7417 TACACTAT A ATCTTCTT 5171 6878 UAAGAAGA CUGAUGAG X CGAA AAUAGUGU 7418 ACACTATT A TCTTCTTA 5173 6879 UUUAAGAA CUGAUGAG X CGAA AUAAUAGU 7419 ACTATTAT C TTCTTAAA 5175 6880 GGUUUAAG CUGAUGAG X CGAA AGAUAAUA 7420 TATTATCT T CTTAAACC 5176 6881 UGGUUUAA CUGAUGAG X CGAA AAGAUAAU 7421 ATTATCTT C TTAAACCA CCUGGUUUCUGAUGAGXCGAAAGAAGAUA7422TATCTTCTTAAACCAGG51786882 UCCUGGUUCUGAUGAGXCGAAAAGAAGAU7423ATCTTCTTAAACCAGGA51796883 CCCCCUUUCUGAUGAGXCGAAAUUUUUUC7424GAAAAAATAAAAGGGGG51946884 UUCUGAAACUGAUGAGXCGAAAUCCCACC7425GGTGGGATTTTTCAGAA52116885 5212 6886 UUUCUGAA CUGAUGAG X CGAA AAUCCCAC 7426 GTGGGATT T TTCAGAAA 5213 6887 UUUUCUGA CUGAUGAG X CGAA AAAUCCCA 7427 TGGGATTT T TCAGAAAA 5214 6888 UUUUUCUG CUGAUGAG X CGAA AAAAUCCC 7428 GGGATTTT T CAGAAAAA 5215 6889 AUUUUUCU CUGAUGAG X CGAA AAAAAUCC 7429 GGATTTTT A AGAAAAAT 5224 6890 UCUUUUUU CUGAUGAG X CGAA AUUUUUCU 7430 AGAAAAAT A AAAAAAGA 5237 6891 GCUACAAA CUGAUGAG X CGAA ACUUUCUU 7431 AAGAAAGT T TTTGTAGC 5238 6892 AGCUACAA CUGAUGAG X CGAA AACUUUCU 7432 AGAAAGTT T TTGTAGCT 5239 6893 CAGCUACA CUGAUGAG X CGAA AAACUUUC 7433 GAAAGTTT T TGTAGCTG 5240 6894 ACAGCUAC CUGAUGAG X CGAA AAAACUUU 7434 AAAGTTTT T GTAGCTGT 5243 6895 UGAACAGC CUGAUGAG X CGAA ACAAAAAC 7435 GTTTTTGT A GCTGTTCA 5249 6896 GGCAACUG CUGAUGAG X CGAA ACAGCUAC 7436 GTAGCTGT T CAGTTGCC 5250 6897 UGGCAACU CUGAUGAG X CGAA AACAGCUA 7437 TAGCTGTT C AGTTGCCA 5254 6898 UUAGUGGC CUGAUGAG X CGAA ACUGAACA 7438 TGTTCAGT T GCCACTAA 5261 6899 CAAUCUCU CUGAUGAG X CGAA AGUGGCAA 7439 TTGCCACT T AGAGATTG 5268 6900 GACUGUGC CUGAUGAG X CGAA AUCUCUUA 7440 TAAGAGAT T GCACAGTC 5276 6901 GAGUUUUU CUGAUGAG X CGAA ACUGUGCA 7441 TGCACAGT C AAAAACTC 5284 6902 UGUGUUUA CUGAUGAG X CGAA AGUUUUUG 7442 CAAAAACT C TAAACACA 5286 6903 AGUGUGUU CUGAUGAG X CGAA AGAGUUUU 7443 AAAACTCT A AACACACT Table VII. Hammerl. Ribozymes to CDP AUCCAAACCUGAUGAGXOGAAAGUGUGUU7444AACACACTAGTTTGGAT52956904 GGAAUCCACUGAUGAGXCGAAACUAGUGU7445ACACTAGTTTGGATTCC52986905 AGGAAUCCCUGAUGAGXCGAAAACUAGUG7446CACTAGTTTGGATTCCT52996906 UAUUUAGGCUGAUGAGXCGAAAUCCAAAC7447GTTTGGATTCCTAAATA53046907 AUAUUUAGCUGAUGAGXCGAAAAUCCAAA7448TTTGGATTCCTAAATAT53056908 AAAAUAUUCUGAUGAGXCGAAAGGAAUCC7449GGATTCCTAAATATTTT53086909 CUUGAAAACUGAUGAGXCGAAAUUUAGGA7450TCCTAAATATTTTCAAG53126910 UUCUUGAACUGAUGAGXCGAAAUAUUUAG7451CTAAATATTTTCAAGAA53146911 UUUCUUGACUGAUGAGXCGAAAAUAUUUA7452TAAATATTTTCAAGAAA53156912 UUUUCUUGCUGAUGAGXCGAAAAAUAUUU7453AAATATTTTCAAGAAAA53166913 CUUUUCUUCUGAUGAGXCGAAAAAAUAUU7454AATATTTTCAAGAAAAG53176914 AACGAGAACUGAUGAGXCGAAAUUCUUUU7455AAAAGAATCTTCTCGTT53296915 CAAACGAGCUGAUGAG53316916 X CGAA AAGAATCTTCTOGTTTG7456 5332 6917 XCGAAAAGAUUCU7457AGAATCTTCTCGTTTGACUGAUGAG UUUCAAACCUGAUGAGXCGAAAGAAGAUU7458AATCTTCTCGTTTGAAA53346918 AAGUUUCACUGAUGAGXCGAAACGAGAAG7459CTTCTCGTTTGAAACTT53376919 AAAGUUUCCUGAUGAGXCGAAAACGAGAA7460TTCTCGTTTGAAACTTT53386920 UUAAUUCACUGAUGAGXCGAAAGUUUCAA7461TTGAAACTTTGAATTAA53456921 UUUAAUUCCUGAUGAGXCGAAAAGUUUCA7462TGAAACTTTGAATTAAA53466922 UUUAUUUUCUGAUGAGXCGAAAUUCAAAG7463CTTTGAATTAAAATAAA53516923 UUUUAUUUCUGAUGAGXCGAAAAUUCAAA7464TTTGAATTAAAATAAAA53526924 AUGUGUUUCUGAUGAGXCGAAAUUUUAAU7465ATTAAAATAAAACACAT53576925 5366 6926 GUGGAGUA CUGAUGAG X CGAA AUGUGUUU 7466 AAACACAT T TACTCCAC 5367 6927 XCGAAAAUGUGUU7467AACACATTTACTCCACACUGAUGAG CUGUGGAGCUGAUGAGXCGAAAAAUGUGU7468ACACATTTACTCCACAG53686928 Where"Xt'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.

Table VIII. Sequences for controls & Hammerhead and Hammerhead-like Ribozymes SEQ. I. D. RPI Sequence ND. Mmher gscscscsugccUGAuGaggccguuaggccGaaAgucgagB19614240 gsuscsusgaccUGAuGaggccguuaggccGaaAuuugcaB27814244 gscsusgsugccUGAuGaggccguuaggccGaaAcaagugB20414252 gsgscsgsccacUGAuGaggccguuaggccGaaAagguggB28114260 gsasusgsugccUGAuGaggccguuaggccGaaAuuucuuB358114336 gsususgsgaacUGAuGaggccguuaggccGaaAuuuuucB350414341 csususgsaagcUGAuGaggccguuaggccGaaAacuuuuB499314437 csgsgsasugacUGAuGaggccguuaggccGaaAguuucgB509014452 csascsgsguccUGAuGaggccguuaggccGaaAcgagacBIR113196 cscsasgsgcucUGAuGaggccguuaggccGauAaugcgcBIR213201 6929 c ucu ctGAuGa c ccGaa Icucuuc B 6930 IccuucuBcUGAuGaggccguuaggccGaa 6931 IgguggaBcUGAuGaggccguuaggccGaa 6932 IuaguagBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcacaacB6933gsascsasauu cUGAuGaggccguuaggccGaaIugacccB6934uscscsusucc cUGAuGaggccguuaggccGaaIgugaagB6935usgscsusuag 6936 cau cUGAuGaggccguuaggccGaa Iugcagc B 6937 IuagaggBcUGAuGaggccguuaggccGaa 6938 a5c5g5g5gug cUGAuGaggccguuaggccGaa Igguggc B 6939 u5a5g5u5aga cUGAuGaggccguuaggccGaa Iccacag B 6940 IggugaacUGAuGaggccguuaggccGaa B cUGAuGaggccguuaggccGaaIcuggagB6941gsgsgsgsuga 69426942gsasgsgsggu BIcugugg 6943 IcacaggBcUGAuGaggccguuaggccGaa 6944 IugggggBcUGAuGaggccguuaggccGaa 6945 ccc cDGaggccguuaggccGaa Icgaguc B 6946 IcccuggBcUGAuGaggccguuaggccGaa 6947 IacccagBcUGAuGaggccguuaggccGaa 69486948asususgsugc BIcuugua 69496949gsgsgsgsuga BIgaggcc 69506950gsascsgsggu BIgggugg 6951 c c eGaa I B 6952 c c cGaa 2 B 6953 c, cL7GAuGaggccguuaggccGaa Iacgggu B 6954 IuuaacaBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIuugucgB6955asgsgsusggu 6956 IagggguBcUGAuGaggccguuaggccGaa 6957 g5g5a5c5ggg cUGAuGaggccguuaggccGaa Iggggug B 6958 g5u5c5a5cca cUGAuGaggccguuaggccGaa Icuggac B 6959 IgcguggBcUGAuGaggccguuaggccGaa 6960 IggugcaBcUGAuGaggccguuaggccGaa 6961 c c c cGaa Iacacac B 6962 IucgucuBcUGAuGaggccguuaggccGaa 6963 c c cguuaggccGaa Igggugc B Table VIII. Sequences for controls & Hammerhead and Hammerhead-like Ribozymes cUGAuGaggccguuaggccGaaIcugcuuB6964csasgsasgag 69656965asasususuga BIugcaau cUGAuGaggccguuaggccGaaIuaacaaB6966gscsusgscuc 69676967asasusgsaac BIcuugcc 6968 IcagccuBcUGAuGaggccguuaggccGaa 6969 IcuucauBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIuuuucuB6970ususcsasaug 6971 IguuuucBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIgguuuuB6972ascsususcaa 69736973asgsususgga BIauuuuu 6974 IaagauuBcUGAuGaggccguuaggccGaa 6975 IgaagauBcUGAuGaggccguuaggccGaa 6976 IcacaguBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIuugaagB6977ususususuuc 6978 IaaacauBcUGAuGaggccguuaggccGaa 6979 c c c ccGaa I caa B 69806980asgsgsasgaa BIcauggu 6981 c cUGRuGaggccguuaggccGaa Igcaugg B 6982 cuc c ccGaa Igcauag B 6983 IcagucuBcUGAuGaggccguuaggccGaa 6984 IuaaaaaBcUGAuGaggccguuaggccGaa 6985 c acu c c ccGaa I B cUGAuGaggccguuaggccGaaIcacuggB6986ascsususgcc 6987 c c ccGaa I 8 6988 IccuuuuBcUGAuGaggccguuaggccGaa 6989 IgaauucBcUGAuGaggccguuaggccGaa 6990 IaccuuuBcUGAuGaggccguuaggccGaa 6991 c caa cUGAuGa cguuaggccGaa Iagaccu B 6992 cOGAuGa cGaa Icuccau B 6993 IccauauBcUGAuGaggccguuaggccGaa 6994 IcugcugBcUGAuGaggccguuaggccGaa 6995 c c cGaa I B 6996 acu cguuaggccGaa Iucc B 6997 IccguagBcUGAuGaggccguuaggccGaa 6998 IaauuggBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcccucgB6999csusususugc 7000 IaaacuuBcUGAuGaggccguuaggccGaa 7001 u5a5a5g5uua cUGAuGaggccguuaggccGaa Iuuccug B 7002 IuuaaguBcUGAuGaggccguuaggccGaa 7003 IuaaguuBcUGAuGaggccguuaggccGaa 7004 u5c5c5u5guu cUGAuGaggccguuaggccGaa Icacggc B cUGAuGaggccguuaggccGaaIuuggcaB7005csasgsusucc 70067006usgsgsusgcu BIucgaug 7007 u5u5c5u5uga cUGAuGaggccguuaggccGaa Icggcag B 7008 IcacuucBcUGAuGaggccguuaggccGaa 7009 g5g5u5u5gga cUGAuGaggccguuaggccGaa Icauucu B 7010 IcaguggBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIgcugcaB7011usgsususguu 7012 a5c5u5c5gac cUGAuGaggccguuaggccGaa Icgcuga B 7013 IgaagaaBcUGAuGaggccguuaggccGaa Table VIII. Sequences for controls & Hammerhead and Hammerhead-like Ribozymes cUGAuGaggccguuaggccGaaIauguggB7014asasgsasugc 7015 IcuuugaBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIgcuuugB7016asgscsascga 70177017usgsgsusugg BIuacugg cUGAuGaggccguuaggccGaaIguacugB7018csusgsgsuug cUGAuGaggccguuaggccGaaIaggaggB7019csgsasusgac 7020 IuuucgaBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIuaaggcB7021asusgsgsaca 7022 a5c5u5g5gau cUGAuGaggccguuaggccGaa Iacaugu B cUGAuGaggccguuaggccGaaIgacaug7023csascsusgga B 7024 c aaa cUGAuGaggccguuaggccGaa Iucuc B 7025 IcucuucBcUGAuGaggccguuaggccGaa 7026 IccuucuBcUGAuGaggccguuaggccGaa 7027 c c cGaa I B 7028 IuaguagBcUGAuGaggccguuaggccGaa 7029 IcacaacBcUGAuGaggccguuaggccGaa 7030 IugacccBcUGAuGaggccguuaggccGaa 7031 IgugaagBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIugcagcB7032ususasascau 7033 asgscsusugu cUGAuGaggccguuaggccGaa Iuagagg B 7034 c c ccGaa Igguggc B 7035 IccacagBcUGAuGaggccguuaggccGaa 7036 IggugaaBcUGAuGaggccguuaggccGaa 7037 cccGaa Icuggag B 7038 IcuguggBcUGAuGaggccguuaggccGaa 7039 IcacaggBcUGAuGaggccguuaggccGaa 7040 c5u5g5g5acg cUGAuGaggccguuaggccGaa Iuggggg B 7041 g5u5u5g5ccc cUGAuGaggccguuaggccGaa Icgaguc B 7042 IcccuggBcUGAuGaggccguuaggccGaa 7043 IacccagBcUGAuGaggccguuaggccGaa 7044 a5u5u5g5ugc cUGAuGaggccguuaggccGaa Icuugua B 7045 g5g5g5g5uga cUGAuGaggccguuaggccGaa Igaggcc B 7046 IggguggBcUGAuGaggccguuaggccGaa 7047 c5a5u5a5agg cUGAuGaggccguuaggccGaa Igugguu B 7048 a5u5a5a5ggu cUGAuGaggccguuaggccGaa Iugguug B 7049 c5c5a5u5gcu cUGAuGaggccguuaggccGaa Iacgggu B 7050 IuuaacacUGAuGaggccguuaggccGaa B 7051 a5g5g5u5ggu cUGAuGaggccguuaggccGaa Iuugucg B cUGAuGaggccguuaggccGaaIagggguB7052csasgscsagc cUGAuGaggccguuaggccGaaIggggugB7053gsgsascsggg 7054 IcuggacBcUGAuGaggccguuaggccGaa 7055 IgcguggBcUGAuGaggccguuaggccGaa 70567056csasgscsuga BIggugca 7057 IacacacBcUGAuGaggccguuaggccGaa 7058 IucgucuBcUGAuGaggccguuaggccGaa 7059 IgggugcBcUGAuGaggccguuaggccGaa 7060 c5a5g5a5gag cUGAuGaggccguuaggccGaa Icugcuu B 7061 a5a5u5u5uga cUGAuGaggccguuaggccGaa Iugcaau B 7062 gscsusgscuc BIuaacaa 7063 a, atu, g, aac cUGkuGaggccguuaggccGaa Icuugcc B Table VIII. Sequences for controls & Hammerhead and Hammerhead-like Ribozymes cUGAuGaggccguuaggccGaaIcagccuB7064asasuscscuu 7065 asgsasgsucu Icuucau B 7066 IuuuucuBcUGAuGaggccguuaggccGaa 7067 IguuuuccUGAuGaggccguuaggccGaa B 7068 IgguuuuBcUGAuGaggccguuaggccGaa 70697069asgsususgga BIauuuuu 7070 IaagauuBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIgaagauB7071gscsascsagu 7072 IcacaguBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIuugaagB7073ususususuuc cUGAuGaggccguuaggccGaaIaaacauB7074asusgscsccu 7075 IugucaaBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcaugguB7076asgsgsasgaa cUGAuGaggccguuaggccGaaIgcauggB7077usasgsgsaga 7078 IgcauagBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcagucuB7079usasasgsaac 7080 g5a5c5c5aag cUGAuGaggccguuaggccGaa Iuaaaaa B cUGAuGaggccguuaggccGaaIgcaagaB7081csasgscsacu 7082 IcacuggBcUGAuGaggccguuaggccGaa 7083 IugcuccBcUGAuGaggccguuaggccGaa 7084 IccuuuuBcUGAuGaggccguuaggccGaa 7085 IgaauucBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIaccuuuB7086gscscsasaug 7087 IagaccuBcUGAuGaggccguuaggccGaa 70887088asuscsusgca Icuccau B 7089 IccauauBcUGAuGaggccguuaggccGaa 7090 c5u5c5g5aug cUGAuGaggccguuaggccGaa Icugcug B 7091 c5a5c5u5cga cUGAuGaggccguuaggccGaa Iugcugc B 70927092csuscsgsacu BIuccccg 7093 IccguagBcUGAuGaggccguuaggccGaa 7094 IaauuggBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcccucgB7095csusususugc cUGAuGaggccguuaggccGaaIaaacuuB7096csuscsusuga 7097 u5a5a5g5uua cUGAuGaggccguuaggccGaa Iuuccug B 7098 asusgsusgua cUGAuGaggccguuaggccGaa Iuuaagu B 7099 IuaaguuBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcacggcB7100uscscsusguu 7101 csasgsusucc BIuuggca 7102 IucgaugBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcggcagB7103ususcsusuga cUGAuGaggccguuaggccGaaIcacuucB7104ascsususuga 71057105gsgsususgga BIcauucu 7106 gsascsasggu cUGAuGaggccguuaggccGaa Icagugg B 71077107usgsususguu BIgcugca 71087108ascsuscsgac BIcgcuga 7109 IgaagaaBcUGAuGaggccguuaggccGaa 7110 IauguggBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIcuuugaB7111gscsascsgau 7112 a5g5c5a5cga cUGAuGaggccguuaggccGaa Igcuuug B cUGAuGaggccguuaggccGaaIuacuggB7113usgsgsusugg Table VIII. Sequences for controls & Hammerhead and Hammerhead-like Ribozymes 7114 IguacugBcUGAuGaggccguuaggccGaa 7115 c5g5a5u5gac cUGAuGaggccguuaggccGaa Iaggagg B 71167116gsgsasusgag BIuuucca 7117 aca cUGAuGaggccguuaggccGaa I B 7118 cUGAuGaggccguuaggccGaa IacauH 7119 c cguuaggccGaa I B 7120 IagucuccUGAuGaggccguuaggccGaa B 7121 a5g5c5u5ugu cUGAuGaggccguuaggccGaa Iuagagg B cUGAuGaggccguuaggccGaaIggugaaB7122csusgscsuua 7123 g5g5g5g5uga cUGAuGaggccguuaggccGaa Icuggag B 7124 IcuguggBcUGAuGaggccguuaggccGaa 7125 c5u5u5c5cug cUGAuGaggccguuaggccGaa Iacccag B 7126 IgaggccBcUGAuGaggccguuaggccGaa cUGAuGaggccguuaggccGaaIggguggB7127gsascsgsggu cUGAuGaggccguuaggccGaaIugguugB7128asusasasggu cUGAuGaggccguuaggccGaaIacggguB7129cscsasusgcu 7130 IgggugcBcUGAuGaggccguuaggccGaa 7131 a5g5u5u5gga cUGAuGaggccguuaggccGaa Iauuuuu B 71327132ususgsasagc BIcacagu cUGAuGaggccguuaggccGaaIccuuuuB7133cscsascsaua 7134 IaaacuuBcUGAuGaggccguuaggccGaa 7135 IcgcugaBcUGAuGaggccguuaggccGaa 7136 a5a5g5a5ugc cUGAuGaggccguuaggccGaa Iaugugg B 7137 IgcuuugBcUGAuGaggccguuaggccGaa 7L38 cgcGaa I B cUGAuGaggccguuaggccGaaIacauguB7139ascsusgsgau 7140 IagucucBcUGAuGaggccguuaggccGaa 7141 CUUCAAGGACAUCGUCCGGGaugguBGgaggaaacucC 7142 gcauGcacuaugcgcgaugaucuaccBuGAUs2g 7243 asususgc uGAUs2g gcaugcacuaugc gcg auaucuuugg B lower case = 2'OMe U = 2'-C-Allyl-U G, A, U= ribo G, A, U s = phosphorothioate linkages S2=dithioate-linkages B = inverted abasic I=ribo-Inosine