Method and reagent for the induction of graft tolerance and reversal of immune responses

Abstract

The present invention relates to nucleic acid molecules which block synthesis and/or expression of an mRNA encoding B7-1, B7-2, B7-3 and/or CD40.

Description

BACKGROUND OF THE INVENTION

[0002] This invention relates to methods for the induction of graft tolerance, treatment of autoimmune diseases, inflammatory disorders and allergies in particular, by inhibition of B7-1, B7-2, B7-3 and CD40.

[0003] The following is a discussion of relevant art, none of which is admitted to be prior art to the present invention.

[0004] An adaptive immune response requires activation, clonal expansion, and differentiation of a class of cells termed T lymphocytes (T cells). T cell activation is a multi-step process requiring several signalling events between the T cell and an antigen presenting cell. The ensuing discussion details signals that are exchanged between T cells and antigen presenting B cells. Similar pathways are thought to occur between T cells and other antigen presenting cells such as monocytes or follicular dendritic cells.

[0005] T cell activation is initiated when the T-cell receptor (TCR) binds to a specific antigen that is associated with the MHC proteins on the surface of an antigen presenting cell. This primary stimulus activates the T cell and induces expression of CD40 ligand (CD40L) on the surface of the T cell. CD40L then interacts with its cognate receptor, CD40, which is constitutively expressed on the surface of B cells; CD40 transduces the signal leading to B cell activation. B cell activations result in the expression of B7-1, B7-2 and/or B7-3, which in turn interacts with constitutively expressed CD28 on the surface of T cells. The interaction generates a secondary co-stimulatory signal that is required to fully activate the T cell. Complete T cell activation via the T cell receptor and CD28 leads to cytokine secretion, clonal expansion, and differentiation. If the T cell receptor is engaged, absence of this secondary co-stimulus mediated by CD28, then the T cell is inactivated, either by clonal anergy (non-responsiveness or reduced reactivity of the immune system to specific antigen(s)) or clonal deletion (Jenkins et al., 1987 Proc. Natl. Acad. Sci. USA 84, 5409). Thus, engagement of the TCR without a concommitant costimulatory signal results in a state of tolerance toward the specific antigen recognized by the T cell. This co-stimulatory signal can be mediated by the binding of B7-1 or B7-2 or B7-3, present on activated antigen-presenting cells, to CD28, a receptor that is constitutively expressed on the surface of the T cell (Marshall et al., 1993 J Clin Immun 13, 165-174; Linsley, et al., 1991 J Exp Med 173, 721; Koulova et al., 1991 J Exp Med 173, 759; Harding et al., 1992 Nature 356, 607).

[0006] Several homologs of B7 (now known as B7-1; Cohen, 1993 Science 262, 844) are expressed in activated B cells (Freeman et al., 1993 Science 262, 907; Lenschow et al., 1993 Proc Natl Acad Sci USA 90, 11054; Azuma et al., 1993 Nature 366, 76; Hathcock et al., 1993 Science 262, 905; Freeman et al., 1993 Science 262, 909). B7-1 and B7-3 are only expressed on the surface of a subset of B cells after 48 hours of contact with T cells. In contrast, B7-2 mRNA is constitutively expressed by unstimulated B cells and increases 4-fold within 4 hours of activation (Freeman et al., 1993 Science 262, 909; Boussiotis et al., 1993 Proc Natl Acad Sci USA 90, 11059). Since T cells commit to either the anergy or the activation pathway within 12-24 hours of the initial TCR signal, it is thought that B7-2 is the molecule responsible for the primary costimulatory signal. B7-1 and B7-3 may provide a subsequent signal necessary for clonal expansion. Antibodies to B7-2 completely block T cell proliferation in a mixed lymphocyte reaction (Azuma et al., 1993 supra), supporting the central role of B7-2 in T cell activation. These experiments indicate that inhibition of B7-2 expression (for example with a ribozyme) would likely induce anergy. Similarly, inhibition of CD40 expression by a ribozyme would prevent B7-2 upregulation and could induce tolerance to specific antigens.

[0007] B7 (B7-1) is a 60 KD modified trans-membrane glycoprotein usually present on the surface of antigen presenting cells (APC). B7 has two ligands—CD28 and CTLA4. Interaction of B7-1 with CD28 and/or CTLA4 causes activation of T cell responses (Janeway and Bottomly, 1994 Cell 76, 275).

[0008] B7-2 is a 70 KD (34 KD unmodified) trans-membrane glycoprotein found on the surface of APCs. B7-2 encodes a 323 amino-acid protein which is 26% identical to human B7-1 protein. Like B7-1, CD28 and CTLA4 are selectively bound by B7-2. B7-2, unlike B7-1, is expressed on the surface of unstimulated B cells (Freeman et al., 1993 supra).

[0009] CD40 is a 45-50 KD surface glycoprotein found on the surface of late pre-B cells in bone marrow, mature B cells, bone marrow-derived dendritic cells and follicular dendritic cells (Clark and Ledbetter, 1994 Nature 367, 425).

[0010] Successful organ transplantation currently requires suppression of the recipient's immune system in order to prevent graft rejection and maintain good graft function. The available therapies, including cyclosporin A, FK506 and various monoclonal antibodies, all have serious side effects (Caine, 1992 Transplantation Proceedings 24, 1260; Fuleihan et al., 1994 J. Clin. Invest. 93, 1315; Van Gool et al., 1994 Blood 83, 176). In addition, existing therapies result in general immune suppression, leaving the patient susceptible to a variety of opportunistic infections. The ability to induce a state of long-term, antigen-specific tolerance to the donor tissue would revolutionize the field of organ and tissue transplantation. Since organ graft rejection is mediated by T cell effector function, the goal is to block specifically the activation of the subset of T cells that recognize donor antigens. A limitation in the field of transplantation is the supply of donor organs (Nowak 1994 Science 266, 1148). The ability to induce donor-specific tolerance would substantially increase the chances of successful allographs, xenographs, thereby greatly increasing the donor pool.

[0011] Such transplantation includes grafting of tissues and/or organ ie., implantation or transplantation of tissue and/or organs, from the body of an individual to a different place within the same or different individual. Transplantation also involve grafting of tissues and/or organs from one area of the body to another. Transplantation of tissues and/or organs between genetically dissimilar animals of the same species is termed as allogeneic transplantation. Transplantation of animal organs into humans is termed xenotransplants (for a review see Nowak, 1994 Science 266, 1148).

[0012] One therapy currently being developed that has similar potential to induce antigen-specific tolerance is treatment with a CTLA4-Ig fusion protein. “CTLA4” is a homologue of CD28 that binds B7-1 and B7-2 with high affinity. The engineered, soluble fusion protein, CTLA4-Ig, binds B7-1, thereby blocking its interaction with CD28. The results of CTLA4-Ig treatment in animal studies are mixed. CTLA4-Ig treatment significantly enhanced survival rates and ameliorated the symptoms of graft-versus host disease in a murine bone marrow tranplant model (Blazer et al., 1994 Blood 83, 3815). CTLA4-Ig induced long-term (>110 days) donor-specific tolerance in pancreatic islet xenographs (Lenschow et al., 1992 Science 257, 789). Conversely, in another study CTLA4-Ig treatment delayed but did not ultimately prevent cardiac allograft rejection (Turka, et al., 1992 Proc Natl Acad Sci U S A 89, 11102). Mice immunized with sheep erythrocytes in the presence of CTLA4-Ig failed to mount a primary immune response (Linsley, et al., 1992 Science 257, 792). A secondary immunization did elicit some response, however, indicating incomplete tolerance. Interestingly, identical results were obtained when CTLA4-Ig was administered 2 days after primary immunization, leading the authors to conclude that CTLA4-Ig blocked amplification rather than initiation of the immune response. Since CTLA4-Ig has been shown to dissociate more rapidly from B7-2 compared with B7-1, this may explain the failure to induce long term tolerance in this model (Linsley et al., 1994 Immunity 1, 793).

[0013] CTLA4:Ig has recently been shown to ameliorate symptoms of spontaneous autoimmune disease in lupus-prone mice (Finck et al., 1994 Science 265, 1225).

[0014] Linsley et al., WO 92/00092 describe B7 antigen as a ligand for CD28 receptor on T cells. The application states that-

[0015] “The B7 antigen, or its fragments or derivatives are reacted with CD28 positive T cells to regulate T cell interactions with other cells . . . B7 antigen or CD28 receptor may be used to inhibit interaction of cells associated with these molecules, thereby regulating T cell responses.”

[0016] De Boer and Conroy, WO 94/01547 describe the use of anti-B7 and anti-CD40 antibodies to treat allograft transplant rejection, graft versus host disease and rhematoid arthritis. The application states that-

[0017] “ . . . anti-B7 and anti-CD40 antibodies . . . can be used to prevent or treat an antibody-mediated or immune system disease in a patient.”

[0018] Since signalling via CD40 precedes induction of B-7, blocking the CD40-CD40L interaction would also have the potential to produce tolerance. According to one report, simultaneous treatment of mice with antibodies to CD40L and sheep red blood cells produced antigen-specific tolerance for up to 3 weeks following cessation of treatment (Foy et al., 1993 J Exp Med 178, 1567). Anti-CD40L also produces antigen specific tolerance in a pancreatic islet transplant model (R. Noelle, personal communication). Targeted inhibition of CD40 expression in B cells in addition to B7 would therefore afford double protection against activation of T cells.

[0019] Therapeutic agents used to prevent rejection of a transplanted organ are all cytotoxic compounds or antibodies designed to suppress the cell-mediated immune system. The side effects of these agents are those of immunosuppression and infections. The primary approved agents are azathioprine, corticosteroids, cyclosporine; the antibodies are antilymphocyte or antithymocyte globulins. All of these are given to individuals who have been as closely matched as possible to their donors by both major and minor histocompatibility typing. Since the principal problem in transplantation is an antigenic mismatch and the resulting need for cytotoxic therapy, any therapeutic improvement which decreases the local immune response without general immunosuppression should capture the transplant market.

[0020] Cyclosporine: At the end of the 1970's and early 1980's the introduction of cyclosporine revolutionized the transplantation field. It is a potent immunosuppressant which can inhibit immunocompetent lymphocytes specifically and reversibly. Its primary mechanism of action appears to be inhibition of the production and release of interleukin-2 by T helper cells. In addition it also interferes with the release of interleukin-1 by macrophages, as well as proliferation of B lymphocytes. It was approved by the FDA in 1983 and by 1989 was almost universally given to transplant recipients. At first it was believed that the toxicity and side effects from cyclosporine were minimal and it was hailed as a “wonder drug.” Numerous side effects have been progressively cited, including the appearance of lymphomas, especially in the gastrointestinal tract; acute and chronic nephrotoxicity; hypertension; hepatotoxicity; hirsutism; anemia; neurotoxicity; endocrine and neurological complications; and gastrointestinal distress. It is now widely acknowledged that the non-specific side effects of the drug demand caution and close monitoring of its use. One-year survival rates for cadaver kidney transplants treated with cyclosporine is 80%, much better than the 50-60% rates without the drug. The one-year survival is almost 90% for transplants with related donors and the use of cyclosporine.

[0021] Azathioprine: In addition to cyclosporine, azathioprine is used for transplant patients. Azathioprine is one of the mercaptopurine class of drugs and inhibits nucleic acid synthesis. Patients are maintained indefinitely on daily doses of 1 mg/kg or less, with a dosage adjusted in accordance with the white cell count. The drug may cause depression of bone marrow elements and may cause jaundice.

[0022] Corticosteroids: Prednisone, used in almost all transplant recipients, is usually given in association with azathioprine and cyclosporine. The dosage must be regulated carefully so as so prevent complications such as infection, development of cushingoid features, and hypertension. Usually the initial maintenance prednisone dosage is 0.5 mg/kg/d. This dosage is usually further decreased in the outpatient clinic until maintenance levels of about 10 mg/d for adults are obtained. The exact site of action of corticosteroids on the immune response is not known.

[0023] Antithymoblast or Antilymphocyte Globulin (ALG) and Antithymocyte Globulin (ATG): These are important adjunctive immunosuppressants. They are effective, particularly in induction of immunosuppressive therapy and in the treatment of corticosteroid-resistant rejection. Both ALG and ATG can be made by immunizing horses, rabbits, or sheep; the main source is horses. Lymphocytes from human peripheral blood, spleen, lymph nodes, or thymus serve as the immunogen.

[0024] Tacrolimus: On Apr. 13, 1994 the Food and Drug Administration approved another drug to help prevent the rejection of organ transplants. The drug, tacrolimus, was approved only for use in liver transplant patients. An alternative to cyclosporine, the macrolide immunosuppressant tacrolimus is a powerful and selective anti-T-lymphocyte agent that was discovered in 1984. Tacrolimus, isolated from the fungus Streptomyces tsukubaensis, possesses immunodepressant properties similar to but more potent than cyclosporine. It inhibits both cell-mediated and humoral immune responses. Like cyclosporine, tacrolimus demonstrates considerable interindividual variation in its pharmacokinetic profile. Most clinical studies with tacrolimus have neither been published in their entirety nor subjected to extensive peer review; there is also a paucity of published randomized investigations of tacrolimus vs. cyclosporine, particularly in renal transplantation. Despite these drawbacks, tacrolimus has shown notable efficacy as a rescue or primary immunosuppressant therapy when combined with corticosteroids. The potential for reductional withdrawal of corticosteroid therapy with tacrolimus appears to be a distinct advantage compared with the cyclosporine. This benefit may be enhanced by reduced incidence of infectious complications, hypertension and hypercholesterolemia reported by some investigators. In other respects, the tolerability profile of tacrolimus appears to be broadly similar to that of cyclosporine.

[0025] In addition to induction of graft tolerance, T cell anergy can be used to reverse autoimmune diseases. Autoimmune diseases represent a broad category of conditions. A few examples include insulin-dependent diabetes mellitus (IDDM), multiple schlerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myasthenia gravis (MG), and psoriasis. These seemingly disparate diseases all share the common feature of inappropriate immune response to specific self-antigens. Finck et al. supra have reported that CTLA4Ig treatment of mice blocked auto-antibody production in a mice model of SLE. In fact, this effect was observed even when the CTLA4Ig treatment was initiated during the advanced stages of the disease, suggesting that the autoimmune response was a reversible process.

[0026] Chappel., WO 94/11011 describes methods to treat autoimmune diseases by inducing tolerance to cells, tissues and organs. The application states that-

[0027] “Cells genetically engineered with DNA encoding a plurality of antigens of a cell, tissue, or organ to which tolerance is to be induced. The cells are free of co-stimulatory antigens, such as B7 antigen,. Such cells induce T-cell anergy against the proteins encoded by the DNA, and may be administered to a patient in order to prevent the onset of or to treat an autoimmune disease, or to induce tolerance to a tissue or organ prior to transplantation.”

[0028] Allergic reactions represent an immediate hypersensitivity response to environmental antigens, typically mediated by IgE antibodies. The ability to induce antigen-specific tolerance provides a powerful avenue to alleviate allergies by exposure to the antigen in conjunction with down-regulation of B7-1, B7-2, B7-3 or CD40.

[0029] The specific roles of B7-1, B7-2 and B7-3 in T cell activation remains to be determined. Some studies suggest that their functions are essentially redundant (Hathcock et al 1994 J Exp. Med. 180, 631), or that the differences observed in the kinetics of expression might simply indicate that B7-2 is important in the initiation of the co-stimulatory signal, while B7-1 plays a role in the amplification of that signal. Other studies point to more specific functions. For example, Kuchroo et al., 1995 Cell 80, 707, have reported that blocking B7-1 expression may favor a Th2 response, while blocking B7-2 expression favors a Th1 response. These two helper T cell subpopulations play distinct roles in the immune response and inflammatory disease. Th1 cells are strongly correlated with auto-immune disease. Allergic responses are typically triggered by Th2 response. Therefore, the decision to target B7-1, B7-2, CD40 or a combination of the above will depend to the particular disease application.

SUMMARY OF THE INVENTION

[0030] The invention features novel nucleic acid-based techniques [e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, 2-5 A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups (Cook et al., U.S. Pat. No. 5,359,051)] and methods for their use to induce graft tolerance, to treat autoimmune diseases such as lupus, rheumatoid arthritis, multiple sclerosis and to treatment of allergies.

[0031] In a preferred embodiment, the invention features use of one or more of the nucleic acid-based techniques to induce graft tolerance by inhibiting the synthesis of B7-1, B7-2, B7-3 and CD40 proteins.

[0032] Those in the art will recognize the other potential targets, for e.g., ICAM-1, VCAM-1, β1 integrin (VLA4) are also suitable for treatment with the nucleic acid-based techniques described in the present invention.

[0033] By “inhibit” is meant that the activity of B7-1, B7-2, B7-3 and/or CD40 or level of mRNAs encoded by B7-1, B7-2, B7-3 and/or CD40 is reduced below that observed in the absence of the nucleic acid. In one embodiment, inhibition with ribozymes preferably is below that level observed in the presence of an enzymatically inactive RNA molecule able to bind to the same site on the mRNA, but unable to cleave that RNA.

[0034] By “enzymatic RNA molecule” it is meant an RNA molecule which has complementarity in a substrate binding region to a specified gene target, and also has an enzymatic activity which is active to specifically cleave RNA in that target. That is, the enzymatic RNA molecule is able to intermolecularly cleave RNA and thereby inactivate a target RNA molecule. This complementarity functions to allow sufficient hybridization of the enzymatic RNA molecule to the target RNA to allow the cleavage to occur. One hundred percent complementarity is preferred, but complementarity as low as 50-75% may also be useful in this invention. By “equivalent” RNA to B7-1, B7-2, B7-3 and/or CD40 is meant to include those naturally occurring RNA molecules associated with graft rejection in various animals, including human, mice, rats, rabbits, primates and pigs.

[0035] By “antisense nucleic acid” is meant a non-enzymatic nucleic acid molecule that binds to another RNA (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).

[0036] By “2-5 A antisense chimera” 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 2-5 A-dependent ribonuclease which in turn cleaves the target RNA (Torrence et al., 1993 Proc. Natl. Acad. Sci. USA 90, 1300).

[0037] By “triplex DNA” is meant an oligonucleotide that can bind to a double-stranded DNA in a sequence-specific manner to form a triple-strand helix. Triple-helix formation has been shown to inhibit transcription of the targeted gene (Duval-Valentin et al., 1992 Proc. Natl. Acad. Sci. USA 89, 504).

[0038] By “gene” is meant a nucleic acid that encodes an RNA.

[0039] By “complementarity” is meant a nucleic acid that can form hydrogen bond(s) with other RNA sequence by either traditional Watson-Crick or other non-traditional types (for example, Hoogsteen type) of base-paired interactions.

[0040] Six basic varieties of naturally-occurring enzymatic RNAs are known presently. Each can catalyze the hydrolysis of RNA phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions. Table I summarizes some of the characteristics 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 a 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.

[0041] The enzymatic nature of a ribozyme is advantageous over other technologies, since the concentration of ribozyme necessary to affect a therapeutic treatment is lower. This advantage reflects the ability of the 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 completely eliminate catalytic activity of a ribozyme.

[0042] Ribozymes that cleave the specified sites in B7-1, B7-2, B7-3 and/or CD40 mRNAs represent a novel therapeutic approach to induce graft tolerance and treat autoimmune diseases, allergies and other inflammatory conditions. Applicant indicates that ribozymes are able to inhibit the activity of B7-1, B7-2, B7-3 and/or CD40 and that the catalytic activity of the ribozymes is required for their inhibitory effect. Those of ordinary skill in the art, will find that it is clear from the examples described that other ribozymes that cleave these sites in B7-1, B7-2, B7-3 and/or CD40 mRNAs may be readily designed and are within the invention.

[0043] In preferred embodiments of this invention, the enzymatic nucleic acid molecule is formed in a hammerhead or hairpin motif, but may also be formed in the motif of a hepatitis delta virus, group I intron or RNaseP RNA (in association with an RNA guide sequence) or Neurospora VS RNA. Examples of such hammerhead motifs are described by 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, and Hampel et al., 1990 Nucleic Acids Res. 18, 299, and an example of the hepatitis delta virus motif is described by Perrotta and Been, 1992 Biochemistry 31, 16; of the RNaseP motif by Guerrier-Takada et al., 1983 Cell 35, 849, 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) and of the Group I intron by Cech et al., U.S. Pat. No. 4,987,071. 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.

[0044] In a preferred embodiment the invention provides a method for producing a class of enzymatic cleaving agents which exhibit a high degree of specificity for the RNA of a desired target. The enzymatic nucleic acid molecule is preferably targeted to a highly conserved sequence region of a target mRNAs encoding B7-1, B7-2, B7-3 and/or CD40 proteins such that specific treatment of a disease or condition can be provided with either one or several enzymatic nucleic acids. Such enzymatic nucleic acid molecules can be delivered exogenously to specific cells as required. Alternatively, the ribozymes can be expressed from DNA/RNA vectors that are delivered to specific cells.

[0045] 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 enzymatic nucleic acid motifs (e.g., of the hammerhead or the hairpin structure) are used for exogenous delivery. The simple structure of these molecules increases the ability of the enzymatic nucleic acid to invade targeted regions of the mRNA structure. However, these catalytic RNA molecules can also be expressed within cells from eukaryotic promoters (e.g., 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). Those skilled in the art realize that any ribozyme can be expressed in eukaryotic cells from the appropriate DNA/RNA vector. The activity of such ribozymes can be augmented by their release from the primary transcript by a second ribozyme (Draper et al., PCT WO93/23569, and Sullivan et al., PCT WO94/02595, both hereby incorporated in their totality by reference herein; Ohkawa et al., 1992 Nucleic Acids Symp. Ser., 27, 15-6; Taira et al., 1991, Nucleic Acids Res., 19, 5125-30; Ventura et al., 1993 Nucleic Acids Res.. 21, 3249-55; Chowrira et al., 1994 J. Biol. Chem. 269, 25856).

[0046] Such ribozymes are useful for the prevention of the diseases and conditions discussed above, and any other diseases or conditions that are related to the levels of B7-1, B7-2, B7-3 and/or CD40 activity in a cell or tissue. By “related” is meant that the inhibition of B7-1, B7-2, B7-3 and/or CD40 mRNAs and thus reduction in the level respective protein activity will relieve to some extent the symptoms of the disease or condition.

[0047] 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 preferred embodiments, the ribozymes have binding arms which are complementary to the sequences in Tables II, IV, VI, VIII, X, XII, XIV, XV, XVI, XVII, XVIII and XIX. Examples of such ribozymes are shown in Tables III, V, VI, VII, IX, XI, XIII, XIV, XV, XVI, XVII, XVIII and XIX. Examples of such ribozymes consist essentially of sequences defined in these Tables. By “consists essentially of” is meant that the active ribozyme contains an enzymatic center equivalent to those in the examples, and binding arms able to bind mRNA such that cleavage at the target site occurs. Other sequences may be present which do not interfere with such cleavage.

[0048] In another aspect of the invention, ribozymes that cleave target molecules and inhibit B7-1, B7-2, B7-3 and/or CD40 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 mRNA. 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.

[0049] By “vectors” is meant any nucleic acid- and/or viral-based technique used to deliver a desired nucleic acid.

[0050] 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

[0051] The drawings will first briefly be described.

[0052] Drawings

[0053] FIG. 1 is a diagrammatic representation of the hammerhead ribozyme domain known in the art. Stem II can be ≧2 base-pair long.

[0054] FIG. 2 a is a diagrammatic representation of the hammerhead ribozyme domain known in the art; FIG. 2b is a diagrammatic representation of the hammerhead ribozyme as divided by Uhlenbeck (1987, Nature, 327, 596-600) into a substrate and enzyme portion; FIG. 2c is a similar diagram showing the hammerhead divided by Haseloff and Gerlach (1988, Nature, 334, 585-591) into two portions; and FIG. 2d is a similar diagram showing the hammerhead divided by Jeffries and Symons (1989, Nucl. Acids. Res., 17, 1371-1371) into two portions.

[0055] FIG. 3 is a diagramatic representation of the general structure of a hairpin ribozyme. 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 ≧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.

[0056] FIG. 4 is a representation of the general structure of the hepatitis delta virus ribozyme domain known in the art.

[0057] FIG. 5 is a representation of the general structure of the self-cleaving VS RNA ribozyme domain.

[0058] FIG. 6 is a schematic representation of an RNAseH accessibility assay. Specifically, the left side of FIG. 6 is a diagram of complementary DNA oligonucleotides bound to accessible sites on the target RNA. Complementary DNA oligonucleotides are represented by broad lines labeled A, B, and C. Target RNA is represented by the thin, twisted line. The right side of FIG. 6 is a schematic of a gel separation of uncut target RNA from a cleaved target RNA. Detection of target RNA is by autoradiography of body-labeled, T7 transcript. The bands common to each lane represent uncleaved target RNA; the bands unique to each lane represent the cleaved products.

[0059] Ribozymes

[0060] Ribozymes of this invention block to some extent B7-1, B7-2, B7-3 and/or CD40 production and can be used to treat disease or diagnose such disease. Ribozymes will be delivered to cells in culture, to cells or tissues in animal models of transplantation, autoimmune diseases and/or allergies and to human cells or tissues ex vivo or in viva. Ribozyme cleavage of B7-1, B7-2 and/or CD40 encoded mRNAs in these systems may alleviate disease symptoms.

[0061] Target Sites

[0062] Targets for useful ribozymes can be determined as disclosed in Draper et al., “Method and reagent for treatment of arthritic conditions U.S. Ser. No. 08/152,487, filed Nov. 12, 1993, and hereby incorporated by reference herein in totality. Rather than repeat the guidance provided in those documents here, below are provided specific examples of such methods, not limiting to those in the art. Ribozymes to such targets are designed as described in those applications and synthesized to be tested in vitro and in vivo, as also described.

[0063] The sequence of human and mouse B7-1, B7-2, B7-3 and/or CD40 mRNAs were screened for optimal ribozyme target sites using a computer folding algorithm. Hammerhead or hairpin ribozyme cleavage sites were identified. These sites are shown in Tables II, IV, VII, VII, X, XII, XIV, XV, XVI, XVII, XVIII and XIX (All sequences are 5′ to 3′ in the tables) The nucleotide base position is noted in the Tables as that site to be cleaved by the designated type of ribozyme. While mouse and human sequences can be screened and ribozymes thereafter designed, the human targeted sequences are of most utility. However, as discussed in Stinchcomb et al., “Method and Composition for Treatment of Restenosis and Cancer Using Ribozymes,” filed May 18, 1994, U.S. Ser. No. 08/245,466, mouse targeted ribozymes may be useful to test efficacy of action of the ribozyme prior to testing in humans. The nucleotide base position is noted in the Tables as that site to be cleaved by the designated type of ribozyme.

[0064] Hammerhead or hairpin ribozymes were designed that could bind and were individually analyzed by computer folding (Jaeger et al., 1989 Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.

[0065] Referring to FIG. 6, mRNA is screened for accessible cleavage sites by the method described generally in McSwiggen, U.S. patent application Ser. No. 07/883,849 filed on May 1, 1992, entitled “Assay for ribozyme target site”, hereby incorporated by reference herein. Briefly, DNA oligonucleotides representing potential hammerhead or hairpin ribozyme cleavage sites were synthesized. A polymerase chain reaction is used to generate substrates for T7 RNA polymerase transcription from human and mouse B7-1, B7-2 and CD40 cDNA clones. Labeled RNA transcripts are synthesized in vitro from the templates. The oligonucleotides and the labeled transcripts were annealed, RNAseH was added and the mixtures were incubated for the designated times at 37° C. Reactions are stopped and RNA separated on sequencing polyacrylamide gels. The percentage of the substrate cleaved is determined by autoradiographic quantitation using a Phosphorimaging system. From these data, hammerhead or hairpin ribozyme sites are chosen as the most accessible.

[0066] Ribozymes of the hammerhead or hairpin motif are designed to anneal to various sites in the mRNA message. The binding arms are complementary to the target site sequences described above. The ribozymes are chemically synthesized. The method of synthesis used follows the procedure for normal RNA synthesis as described in Usman et al., 1987 J. Am. Chem. Soc., 109, 7845 and in Scaringe et al., 1990 Nucleic Acids Res., 18, 5433 and makes 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 were synthesized in two parts and annealed to reconstruct the active ribozyme (Chowrira and Burke, 1992 Nucleic Acids Res., 20, 2835-2840). Ribozymes were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). All ribozymes are modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-O-methyl, 2′-H (for a review see Usman and Cedergren, 1992 TIBS 17, 34). Ribozymes are purified by gel electrophoresis using general methods or are purified by high pressure liquid chromatography (HPLC; See Usman et al., Synthesis, deprotection, analysis and purification of RNA and ribozymes, filed May, 18, 1994, U.S. Ser. No. 08/245,736 the totality of which is hereby incorporated herein by reference) and are resuspended in water.

[0067] The sequences of the ribozymes that are chemically synthesized, useful in this study, are shown in Tables III, V, VI, VII, IX, XI, XIII, XIV, XV, XVI, XVII, XVIII and XIX. Those in the art will recognize that these sequences are representative only of many more such sequences where the enzymatic portion of the ribozyme (all but the binding arms) is altered to affect activity. For example, stem-loop II sequence of hammerhead ribozymes listed in Tables III and V (5′-GGCCGAAAGGCC-3′) can be altered (substitution, deletion, and/or insertion) to contain any sequences provided a minimum of two base-paired stem structure can form. Similarly, stem-loop IV sequence of hairpin ribozymes listed in Tables VI and VII (5′-CACGUUGUG-3′) can be altered (substitution, deletion, and/or insertion) to contain any sequence, provided a minimum of two base-paired stem structure can form. The sequences listed in Tables III, V, VI, VII, IX, XI, XII, XIV, XV, XVI, XVII, XVIII and XIX may be formed of ribonucleotides or other nucleotides or non-nucleotides. Such ribozymes are equivalent to the ribozymes described specifically in the Tables.

[0068] Optimizing Ribozyme Activity

[0069] Ribozyme activity can be optimized as described by Stinchcomb et al., supra. The details will not be repeated here, but include altering the length of the ribozyme binding arms (stems I and III, see FIG. 2c), or chemically synthesizing ribozymes with modifications that prevent their degradation by serum ribonucleases (see e.g., Eckstein et al, International Publication No. WO 92/07065; Perrault et al., 1990 Nature 344, 565; Pieken et al., 1991 Science 253, 314; Usman and Cedergren, 1992 Trends in Biochem. Sci. 17, 334; Usman et al., International Publication No. WO 93/15187; and Rossi et al., International Publication No. WO 91/03162, as well as Usman, N. et al. U.S. patent application Ser. No. 07/829,729, and Sproat, European Patent Application 92110298.4 which describe various chemical modifications that can be made to the sugar moieties of enzymatic RNA molecules). Modifications which enhance their efficacy in cells, and removal of stem II bases to shorten RNA synthesis times and reduce chemical requirements are desired. (All these publications are hereby incorporated by reference herein.),

[0070] Sullivan, et al., supra, describes the general methods for delivery of enzymatic RNA molecules. Ribozymes may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres. For some indications, ribozymes may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the RNA/vehicle combination is locally delivered by direct injection or by use of a 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 ribozyme delivery and administration are provided in Sullivan et al., supra and Draper et al., supra which have been incorporated by reference herein.

[0071] In another preferred embodiment, the ribozyme is administered to the site of B7-1, B7-2, B7-3 and/or CD40 expression (APC) in an appropriate liposomal vesicle. APCs isolated from donor (for example) are treated with the ribozyme preparation (or other nucleic acid therapeutics) ex vivo and the treated cells are infused into recipient. Alternatively, cells, tissues or organs are directly treated with nucleic acids of the present invention prior to transplantation into a recipient.

[0072] Another means of accumulating high concentrations of a ribozyme(s) within cells is to incorporate the ribozyme-encoding sequences into a DNA or RNA expression vector. Transcription of the ribozyme sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol III promoters will be expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers, 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). The above ribozyme transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated virus vectors), or viral RNA vectors (such as retroviral or alphavirus vectors).

[0073] In a preferred embodiment of the invention, a transcription unit expressing a ribozyme that cleaves mRNAs encoded by B7-1, B7-2, B7-3 and/or CD40 are inserted into a plasmid DNA vector or an adenovirus or adeno-associated virus DNA viral vector or a retroviral RNA vector. Viral vectors have been used to transfer genes and lead to either transient or long term gene expression (Zabner et al., 1993 Cell 75, 207; Carter, 1992 Curr. Opi. Biotech. 3, 533). The adenovirus vector is delivered as recombinant adenoviral particles. The DNA may be delivered alone or complexed with vehicles (as described for RNA above). The recombinant adenovirus or AAV particles are locally administered to the site of treatment, e.g. through incubation or inhalation in vivo or by direct application to cells or tissues ex vivo.

[0074] B7-1, B7-2, B7-3 and CD40 are attractive ribozyme targets by several criteria. The molecular mechanism of T cell activation is well-established. Efficacy can be tested in well-defined and predictive animal models. The clinical end-point of graft rejection is clear. Since delivery would be ex vivo, treatment of the correct cell population would be assured. Finally, the disease condition is serious and current therapies are inadequate. Whereas protein-based therapies would induce anergy against all antigens encountered during the several week treatment period, ex vivo ribozyme therapy provides a direct and elegant approach to truly donor-specific anergy.

[0075] Similarly, autoimmune diseases and allergies can be prevented or treated by reversing the devastating course of immune response to self-antigens. Specifically, nucleic acids of this inventions can dampen the response to naturally occuring antigens.

EXAMPLE 1

B7-1, B7-2, B7-3 and/or CD40 Hammerhead Ribozymes

[0076] By engineering ribozyme motifs we have designed several ribozymes directed against B7-1, B7-2, B7-3 and/or CD40 encoded mRNA sequences. These ribozymes were synthesized with modifications that improve their nuclease resistance. The ability of ribozymes to cleave target sequences in vitro was evaluated.

[0077] Several common human cell lines are available that can be induced to express endogenous B7-1, B7-2, B7-3 and/or CD40. Alternatively, murine splenic cells can be isolated and induced, to express B7-1 or B7-2, with IL-4 or recombinant CD40 ligand. B7-1 and B7-2 can be detected easily with monoclonal antibodies. Use of appropriate flourescent reagents and flourescence-activated cell-sorting (FACS) will permit direct quantitation of surface B7-1 and B7-2 on a cell-by-cell basis. Active ribozymes are expected to directly reduce B7-1 or B7-2 expression. Ribozymes targeted to CD40 would prevent induction of B7-2 by CD40 ligand.

[0078] Several animal models of transplantation are available -Mouse, rat, Porcine model (Fodor et al., 1994, Proc. Natl. Acad. Sci. USA 91, 11153); or Baboon (reviewed by Nowak, 1994 Science 266, 1148). B7-1, B7-2, B7-3 and/or CD40 protein levels can be measured clinically or experimentally by FACS analysis. B7-1, B7-2, B7-3 and/or CD40 encoded mRNA levels will be assessed by Northern analysis, RNase-protection, primer extension analysis and/or quantitative RT-PCR. Ribozymes that block the induction of B7-1, B7-2, B7-3 and/or CD40 activity and/or B7-1, B7-2, B7-3 and/or CD40 protein encoding mRNAs by more than 20% in vitro will be identified.

[0079] Several animals models of autoimmune disorders are available—allergic encephalomyelitis (EAE) in Lewis rats (Carlson et al., 1993 Ann. N.Y. Acad. Sci. 685, 86); animal models of multiple sclerosis (Wekerle et al., 1994 Ann. Neurol. 36, s47) and rheumatoid arthritis (van Laar et al., 1994 Chem. Immunol. 58, 206).

[0080] Several animal models of allergy are available and are reviewed by Kemeny and Diaz-Sanchez, 1990, Clin. Exp. Immunol. 82, 423 and Pretolani et al., 1994 Ann. N.Y. Acad. Sci. 725, 247).

[0081] RNA ribozymes and/or genes encoding them will be delivered by either free delivery, liposome delivery, cationic lipid delivery, adeno-associated virus vector delivery, adenovirus vector delivery, retrovirus vector delivery or plasmid vector delivery in these animal model experiments (see above). One dose of a ribozyme vector that constitutively expresses the ribozyme or one or more doses of a stable anti-B7-1, B7-2, B7-3 and/or CD40 ribozymes or a transiently expressing ribozyme vector to donor APC, followed by infusion into the recipient may reduce the incidence of graft rejection. Alternatively, graft tissues may be treated as described above prior to transplantation.

[0082] Diagnostic Uses

[0083] Ribozymes of this invention may be used as diagnostic tools to examine genetic drift and mutations within diseased cells or to detect the presence of B7-1, B7-2, B7-3 and/or CD40 RNA in a cell. The close relationship between ribozyme activity and the structure of the target RNA allows the detection of mutations in any region of the molecule which alters the base-pairing and three-dimensional structure of the target RNA. By using multiple ribozymes described in this invention, one may map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with ribozymes may be used to inhibit gene expression and define the role (essentially) of specified gene products in the progression of disease. In this manner, other genetic targets may be defined as important mediators of the disease. These experiments will lead to better treatment of the disease progression by affording the possibility of combinational therapies (e.g., multiple ribozymes targeted to different genes, ribozymes coupled with known small molecule inhibitors, or intermittent treatment with combinations of ribozymes and/or other chemical or biological molecules). Other in vitro uses of ribozymes of this invention are well known in the art, and include detection of the presence of mRNAs associated with B7-1, B7-2, B7-3 and/or CD40 related condition. Such RNA is detected by determining the presence of a cleavage product after treatment with a ribozyme using standard methodology.

[0084] 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 (i.e., B7-1, B7-2, B7-3 and/or CD40) 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.

[0085] Other embodiments are within the following claims.

TABLE I
Characteristics of Ribozymes
Group I Introns
Size: ˜200 to >1000 nucleotides.
Requires a U in the target sequence immediately 5′ of the cleavage
site.
Binds 4-6 nucleotides at 5′ side of cleavage site.
Over 75 known members of this class. Found in Tetrahymena
thermophila rRNA, fungal mitochondria, chloroplasts, phage T4,
blue-green algae, and others.
RNAseP RNA (M1 RNA)
Size: ˜290 to 400 nucleotides.
RNA portion of a ribonucleoprotein enzyme. Cleaves tRNA
precursors to form mature tRNA.
Roughly 10 known members of this group all are bacterial in origin.
Hammerhead Ribozyme
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.
14 known members of this class. Found in a number of plant
pathogens (virusoids) that use RNA as the infectious agent (FIG. 1)
Hairpin Ribozyme
Size: ˜50 nucleotides.
Requires the target sequence GUC immediately 3′ of the cleavage
site.
Binds 4-6 nucleotides at 5′ side of the cleavage site and a variable
number to the 3′ side of the cleavage site.
Only 3 known member 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 (FIG. 3).
Hepatitis Delta Virus (HDV) Ribozyme
Size: 50-60 nucleotides (at present).
Cleavage of target RNAs recently demonstrated.
Sequence requirements not fully determined.
Binding sites and structural requirements not fully determined,
although no sequences 5′ of cleavage site are required.
Only 1 known member of this class. Found in human HDV (FIG. 4).
Neurospora VS RNA Ribozyme
Size: ˜144 nucleotides (at present)
Cleavage of target RNAs recently demonstrated.
Sequence requirements not fully determined.
Binding sites and structural requirements not fully determined. Only
1 known member of this class. Found in Neurospora VS RNA
(FIG. 5).

[0086]

TABLE II
Human B7-1 Hammerhead Ribozyme Sequences
	SEQ
nt. ID	HH Target
Position	NO	Sequence
8	1	AAACCCU C UGUAAAG
12	2	CCUCUGU A AAGUAAC
17	3	GUAAAGU A ACAGAAG
26	4	CAGAAGU U AGAAGGG
27	5	AGAAGUU A GAAGGGG
41	6	GAAAUGU C GCCUCUC
46	7	GUCGCCU C UCUGAAG
48	8	CGCCUCU C UGAAGAU
56	9	UGAAGAU U ACCCAAA
57	10	GAAGAUU A CCCAAAG
75	11	AAGUGAU U UGUCAUU
76	12	AGUGAUU U GUCAUUG
79	13	GAUUUGU C AUUGCUU
82	14	UUGUCAU U GCUUUAU
86	15	CAUUGCU U UAUAGAC
87	16	AUUGCUU U AUAGACU
88	17	UUGCUUU A UAGACUG
90	18	GCUUUAU A GACUGUA
97	19	AGACUGU A AGAAGAG
110	20	AGAACAU C UCAGAAG
112	21	AACAUCU C AGAAGUG
124	22	GUGGAGU C UUACCCU
126	23	GGAGUCU U ACCCUGA
127	24	GAGUCUU A CCCUGAA
137	25	CUGAAAU C AAAGGAU
145	26	AAAGGAU U UAAAGAA
146	27	AAGGAUU U AAAGAAA
147	28	AGGAUUU A AAGAAAA
163	29	GUGGAAU U UUUCUUC
164	30	UGGAAUU U UUCUUCA
165	31	GGAAUUU U UCUUCAG
166	32	GAAUUUU U CUUCAGC
167	33	AAUUUUU C UUCAGCA
169	34	UUUUUCU U CAGCAAG
170	35	UUUUCUU C AGCAAGC
187	36	UGAAACU A AAUCCAC
191	37	ACUAAAU C CACAACC
200	38	ACAACCU U UGGAGAC
201	39	CAACCUU U GGAGACC
221	40	ACACCCU C CAAUCUC
226	41	CUCCAAU C UCUGUGU
228	42	CCAAUCU C UGUGUGU
441	43	UUCAGCU C UUGGUGC
443	44	CAGCUCU U GGUGCUG
457	45	GGCUGGU C UUUCUCA
459	46	CUGGUCU U UCUCACU
460	47	UGGUCUU U CUCACUU
461	48	GGUCUUU C UCACUUC
463	49	UCUUUCU C ACUUCUG
467	50	UCUCACU U CUGUUCA
468	51	CUCACUU C UGUUCAG
472	52	CUUCUGU U CAGGUGU
473	53	UUCUGUU C AGGUGUU
480	54	CAGGUGU U AUCCACG
481	55	AGGUGUU A UCCACGU
483	56	GUGUUAU C CACGUGA
521	57	ACGCUGU C CUGUGGU
529	58	CUGUGGU C ACAAUGU
537	59	ACAAUGU U UCUGUUG
538	60	CAAUGUU U CUGUUGA
539	61	AAUGUUU C UGUUGAA
543	62	UUUCUGU U GAAGAGC
562	63	ACAAACU C GCAUCUA
567	64	CUCGCAU C UACUGGC
569	65	CGCAUCU A CUGGCAA
601	66	GCUGACU A UGAUGUC
608	67	AUGAUGU C UGGGGAC
622	68	CAUGAAU A UAUGGCC
624	69	UGAAUAU A UGGCCCG
635	70	CCCGAGU A CAAGAAC
651	71	GGACCAU C UUUGAUA
653	72	ACCAUCU U UGAUAUC
654	73	CCAUCUU U GAUAUCA
658	74	CUUUGAU A UCACUAA
660	75	UUGAUAU C ACUAAUA
664	76	UAUCACU A AUAACCU
667	77	CACUAAU A ACCUCUC
672	78	AUAACCU C UCCAUUG
674	79	AACCUCU C CAUUGUG
678	80	UCUCCAU U GUGAUCC
684	81	UUGUGAU C CUGGCUC
691	82	CCUGGCU C UGCGCCC
701	83	CGCCCAU C UGACGAG
716	84	GGCACAU A CGAGUGU
726	85	AGUGUGU U GUUCUGA
729	86	GUGUUGU U CUGAAGU
730	87	UGUUGUU C UGAAGUA
737	86	CUGAAGU A UGAAAAA
751	89	AGACGCU U UCAAGCG
752	90	GACGCUU U CAAGCGG
753	91	ACGCUUU C AAGCGGG
1016	92	CACAGCU U CAUGUGU
1017	93	ACAGCUU C AUGUGUC
1024	94	CAUGUGU C UCAUCAA
1026	95	UGUGUCU C AUCAAGU
1029	96	GUCUCAU C AAGUAUG
1034	97	AUCAAGU A UGGACAU
1042	98	UGGACAU U UAAGAGU
1043	99	GGACAUU U AAGAGUG
1044	100	GACAUUU A AGAGUGA
1054	101	AGUGAAU C AGACCUU
1061	102	CAGACCU U CAACUGG
1062	103	AGACCUU C AACUGGA
1072	104	CUGGAAU A CAACCAA
1090	105	AGAGCAU U UUCCUGA
1091	106	GAGCAUU U UCCUGAU
1092	107	AGCAUUU U CCUGAUA
1093	108	GCAUUUU C CUGAUAA
1099	109	UCCUGAU A ACCUGCU
1107	110	ACCUGCU C CCAUCCU
1112	111	CUCCCAU C CUGGGCC
1122	112	GGGCCAU U ACCUUAA
1123	113	GGCCAUU A CCUUAAU
1127	114	AUUACCU U AAUCUCA
1128	115	UUACCUU A AUCUCAG
1131	116	CCUUAAU C UCAGUAA
1133	117	UUAAUCU C AGUAAAU
1137	118	UCUCAGU A AAUGGAA
1146	119	AUGGAAU U UUUGUGA
1147	120	UGGAAUU U UUGUGAU
1148	121	GGAAUUU U UGUGAUA
1149	122	GAAUUUU U GUGAUAU
1155	123	UUGUGAU A UGCUGCC
1169	124	CUGACCU A CUGCUUU
1175	125	UACUGCU U UGCCCCA
1176	126	ACUGCUU U GCCCCAA
1214	127	GAGAGAU U GAGAAGG
1230	128	AAAGUGU A CGCCCUG
1239	129	GCCCUGU A UAACAGU
1241	130	CCUGUAU A ACAGUGU
1249	131	ACAGUGU C CGCAGAA
1275	132	AAAAGAU C UGAAGGU
1283	133	UGAAGGU A GCCUCCG
1288	134	GUAGCCU C CGUCAUC
1292	135	CCUCCGU C AUCUCUU
1295	136	CCGUCAU C UCUUCUG
1297	137	GUCAUCU C UUCUGGG
1299	138	CAUCUCU U CUGGGAU
1300	139	AUCUCUU C UGGGAUA
1307	140	CUGGGAU A CAUGGAU
1487	141	CCAUGUU U CCAUUCU
1488	142	CAUGUUU C CAUUCUG
1492	143	UUUCCAU U CUGCCAU
1493	144	UUCCAUU C UGCCAUC
1500	145	CUGCCAU C UUGAAUU
1502	146	GCCAUCU U GAAUUGU
1507	147	CUUGAAU U GUCUUGU
1510	148	GAAUUGU C UUGUCAG
1512	149	AUUGUCU U GUCAGCC
1515	150	GUCUUGU C AGCCAAU
1523	151	AGCCAAU U CAUUAUC
1524	152	GCCAAUU C AUUAUCU
1527	153	AAUUCAU U AUCUAUU
1528	154	AUUCAUU A UCUAUUA
1530	155	UCAUUAU C UAUUAAA
1532	156	AUUAUCU A UUAAACA
1534	157	UAUCUAU U AAACACU
1535	158	AUCUAUU A AACACUA
1542	159	AAACACU A AUUUGAG
236	160	UGUGUGU U UUGUAAA
237	161	GUGUGUU U UGUAAAC
238	162	UGUGUUU U GUAAACA
241	163	GUUUUGU A AACAUCA
247	164	UAAACAU C ACUGGAG
258	165	GGAGGGU C UUCUACG
260	166	AGGGUCU U CUAGGUG
261	167	GGGUCUU C UACGUGA
263	168	GUCUUCU A CGUGAGC
274	169	GAGCAAU U GGAUUGU
279	170	AUUGGAU U GUCAUCA
282	171	GGAUUGU C AUCAGCC
285	172	UUGUCAU C AGCCCUG
298	173	UGCCUGU U UUGCACC
299	174	GCCUGUU U UGCACCU
300	175	CCUGUUU U GCACCUG
322	176	CCCUGGU C UUACUUG
324	177	CUGGUCU U ACUUGGG
325	178	UGGUCUU A CUUGGGU
328	179	UCUUACU U GGGUCCA
333	180	CUUGGGU C CAAAUUG
339	181	UCCAAAU U GUUGGCU
342	182	AAAUUGU U GGCUUUC
347	183	GUUGGCU U UCACUUU
348	184	UUGGCUU U CACUUUU
349	185	UGGCUUU C ACUUUUG
353	186	UUUCACU U UUGACCC
354	187	UUCACUU U UGACCCU
355	188	UCACUUU U GACCCUA
362	189	UGACCCU A AGCAUCU
368	190	UAAGCAU C UGAAGCC
404	191	GGAACAU C ACCAUCC
410	192	UCACCAU C CAAGUGU
418	193	CAAGUGU C CAUACCU
422	194	UGUCCAU A CCUCAAU
426	195	CAUACCU C AAUUUCU
430	196	CCUCAAU U UCUUUCA
431	197	CUCAAUU U CUUUCAG
432	198	UCAAUUU C UUUCAGC
434	199	AAUUUCU U UCAGCUC
435	200	AUUUCUU U CAGCUCU
436	201	UUUCUUU C AGCUCUU
782	202	GUGACGU U AUCAGUC
783	203	UGACGUU A UCAGUCA
785	204	ACGUUAU C AGUCAAA
789	205	UAUCAGU C AAAGCUG
800	206	GCUGACU U CCCUACA
801	207	CUGACUU C CCUACAC
805	208	CUUCCCU A CACCUAG
811	209	UACACCU A GUAUAUC
814	210	ACCUAGU A UAUCUGA
816	211	CUAGUAU A UCUGACU
818	212	AGUAUAU C UGACUUU
824	213	UCUGACU U UGAAAUU
825	214	CUGACUU U GAAAUUC
831	215	UUGAAAU U CCAACUU
832	216	UGAAAUU C CAACUUC
838	217	UCCAACU U CUAAUAU
839	218	CCAACUU C UAAUAUU
841	219	AACUUCU A AUAUUAG
844	220	UUCUAAU A UUAGAAG
846	221	CUAAUAU U AGAAGGA
847	222	UAAUAUU A GAAGGAU
855	223	GAAGGAU A AUUUGCU
858	224	GGAUAAU U UGCUCAA
859	225	GAUAAUU U GCUCAAC
863	226	AUUUGCU C AACCUCU
869	227	UCAACCU C UGGAGGU
877	228	UGGAGGU U UUCCAGA
878	229	GGAGGUU U UCCAGAG
879	230	GAGGUUU U CCAGAGC
880	231	AGGUUUU C CAGAGCC
889	232	AGAGCCU C ACCUCUC
894	233	CUCACCU C UCCUGGU
896	234	CACCUCU C CUGGUUG
902	235	UCCUGGU U GGAAAAU
920	236	GAAGAAU U AAAUGCC
921	237	AAGAAUU A AAUGCCA
930	238	AUGCCAU C AACACAA
942	239	CAACAGU U UCCCAAG
943	240	AACAGUU U CCCAAGA
944	241	ACAGUUU C CCAAGAU
952	242	CCAAGAU C CUGAAAC
966	243	CUGAGCU C UAUGCUG
968	244	GAGCUCU A UGCUGUU
975	245	AUGCUGU U AGCAGCA
976	246	UGCUGUU A GCAGCAA
991	247	ACUGGAU U UCAAUAU
992	248	CUGGAUU U CAAUAUG
993	249	UGGAUUU C AAUAUGA
997	250	UUUCAAU A UGACAAC
1315	251	CAUGGAU C GUGGGGA
1324	252	UGGGGAU C AUGAGGC
1334	253	GAGGCAU U CUUCCCU
1335	254	AGGCAUU C UUCCCUU
1337	255	GCAUUCU U CCCUUAA
1338	256	CAUUCUU C CCUUAAC
1342	257	CUUCCCU U AACAAAU
1343	258	UUCCCUU A ACAAAUU
1350	259	AACAAAU U UAAGCUG
1351	260	ACAAAUU U AAGCUGU
1352	261	CAAAUUU A AGCUGUU
1359	262	AAGCUGU U UUACCCA
1360	263	AGCUGUU U UACCCAC
1361	264	GCUGUUU U ACCCACU
1362	265	CUGUUUU A CCCACUA
1369	266	ACCCACU A CCUCACC
1373	267	ACUACCU C ACCUUCU
1378	268	CUCACCU U CUUAAAA
1379	269	UCACCUU C UUAAAAA
1381	270	ACCUUCU U AAAAACC
1382	271	CCUUCUU A AAAACCU
1390	272	AAAACCU C UUUCAGA
1392	273	AACCUCU U UCAGAUU
1393	274	ACCUCUU U CAGAUUA
1394	275	CCUCUUU C AGAUUAA
1399	276	UUCAGAU U AAGCUGA
1400	277	UCAGAUU A AGCUGAA
1412	278	GAACAGU U ACAAGAU
1413	279	AACAGUU A CAAGAUG
1429	280	CUGGCAU C CCUCUCC
1433	281	CAUCCCU C UCCUUUC
1435	282	UCCCUCU C CUUUCUC
1438	283	CUCUCCU U UCUCCCC
1439	284	UCUCCUU U CUCCCCA
1440	285	CUCCUUU C UCCCCAU
1442	286	CCUUUCU C CCCAUAU
1448	287	UCCCCAU A UGCAAUU
1455	288	AUGCAAU U UGCUUAA
1456	289	UGCAAUU U GCUUAAU
1460	290	AUUUGCU U AAUGUAA
1461	291	UUUGCUU A AUGUAAC
1466	292	UUAAUGU A ACCUCUU
1471	293	GUAACCU C UUCUUUU
1473	294	AACCUCU U CUUUUGC
1474	295	ACCUCUU C UUUUGCC
1476	296	CUCUUCU U UUGCCAU
1477	297	UCUUCUU U UGCCAUG
1478	298	CUUCUUU U GCCAUGU
1486	299	GCCAUGU U UCCAUUC

[0087]

TABLE III
Human B7-1 Hammerhead Ribozyme Sequences
nt.	SEQ
Posi-	ID
tion	NO	HH Ribozyme Sequence
8	1057	CUUUACA CUGAUGAGGCCGAAAGGCCGAA AGGGUUU
12	1058	GUUACUU CUGAUGAGGCCGAAAGGCCGAA ACAGAGG
17	1059	CUUCUGU CUGAUGAGGCCGAAAGGCCGAA ACUUUAC
26	1060	CCCUUCU CUGAUGAGGCCGAAAGGCCGAA ACUUCUG
27	1061	CCCCUUC CUGAUGAGGCCGAAAGGCCGAA AACUUCU
41	1062	GAGAGGC CUGAUGAGGCCGAAAGGCCGAA ACAUUUC
46	1063	CUUCAGA CUGAUGAGGCCGAAAGGCCGAA AGGCGAC
48	1064	AUCUUCA CUGAUGAGGCCGAAAGGCCGAA AGAGGCG
56	1065	UUUGGGU CUGAUGAGGCCGAAAGGCCGAA AUCUUCA
57	1066	CUUUGGG CUGAUGAGGCCGAAAGGCCGAA AAUCUUC
75	1067	AAUGACA CUGAUGAGGCCGAAAGGCCGAA AUCACUU
76	1068	CAAUGAC CUGAUGAGGCCGAAAGGCCGAA AAUCACU
79	1069	AAGCAAU CUGAUGAGGCCGAAAGGCCGAA ACAAAUC
82	1070	AUAAAGC CUGAUGAGGCCGAAAGGCCGAA AUGACAA
86	1071	GUCUAUA CUGAUGAGGCCGAAAGGCCGAA AGCAAUG
87	1072	AGUCUAU CUGAUGAGGCCGAAAGGCCGAA AAGCAAU
88	1073	CAGUCUA CUGAUGAGGCCGAAAGGCCGAA AAAGCAA
90	1074	UACAGUC CUGAUGAGGCCGAAAGGCCGAA AUAAAGC
97	1075	CUCUUCU CUGAUGAGGCCGAAAGGCCGAA ACAGUCU
110	1076	CUUCUGA CUGAUGAGGCCGAAAGGCCGAA AUGUUCU
112	1077	CACUUCU CUGAUGAGGCCGAAAGGCCGAA AGAUGUU
124	1078	AGGGUAA CUGAUGAGGCCGAAAGGCCGAA ACUCCAC
126	1079	UCAGGGU CUGAUGAGGCCGAAAGGCCGAA AGACUCC
127	1080	UUCAGGG CUGAUGAGGCCGAAAGGCCGAA AAGACUC
137	1081	AUCCUUU CUGAUGAGGCCGAAAGGCCGAA AUUUCAG
145	1082	UUCUUUA CUGAUGAGGCCGAAAGGCCGAA AUCCUUU
146	1083	UUUCUUU CUGAUGAGGCCGAAAGGCCGAA AAUCCUU
147	1084	UUUUCUU CUGAUGAGGCCGAAAGGCCGAA AAAUCCU
163	1085	GAAGAAA CUGAUGAGGCCGAAAGGCCGAA AUUCCAC
164	1086	UGAAGAA CUGAUGAGGCCGAAAGGCCGAA AAUUCCA
165	1087	CUGAAGA CUGAUGAGGCCGAAAGGCCGAA AAAUUCC
166	1088	GCUGAAG CUGAUGAGGCCGAAAGGCCGAA AAAAUUC
167	1089	UGCUGAA CUGAUGAGGCCGAAAGGCCGAA AAAAAUU
169	1090	CUUGCUG CUGAUGAGGCCGAAAGGCCGAA AGAAAAA
170	1091	GCUUGCU CUGAUGAGGCCGAAAGGCCGAA AAGAAAA
187	1092	GUGGAUU CUGAUGAGGCCGAAAGGCCGAA AGUUUCA
191	1093	GGUUGUG CUGAUGAGGCCGAAAGGCCGAA AUUUAGU
200	1094	GUCUCCA CUGAUGAGGCCGAAAGGCCGAA AGGUUGU
201	1095	GGUCUCC CUGAUGAGGCCGAAAGGCCGAA AAGGUUG
221	1096	GAGAUUG CUGAUGAGGCCGAAAGGCCGAA AGGGUGU
226	1097	ACACAGA CUGAUGAGGCCGAAAGGCCGAA AUUGGAG
228	1098	ACACACA CUGAUGAGGCCGAAAGGCCGAA AGAUUGG
236	1099	UUUACAA CUGAUGAGGCCGAAAGGCCGAA ACACACA
237	1100	GUUUACA CUGAUGAGGCCGAAAGGCCGAA AACACAC
238	1101	UGUUUAC CUGAUGAGGCCGAAAGGCCGAA AAACACA
241	1102	UGAUGUU CUGAUGAGGCCGAAAGGCCGAA ACAAAAC
247	1103	CUCCAGU CUGAUGAGGCCGAAAGGCCGAA AUGUUUA
258	1104	CGUAGAA CUGAUGAGGCCGAAAGGCCGAA ACCCUCC
260	1105	CACGUAG CUGAUGAGGCCGAAAGGCCGAA AGACCCU
261	1106	UCACGUA CUGAUGAGGCCGAAAGGCCGAA AAGACCC
263	1107	GCUCACG CUGAUGAGGCCGAAAGGCCGAA AGAAGAC
274	1108	ACAAUCC CUGAUGAGGCCGAAAGGCCGAA AUUGCUC
279	1109	UGAUGAC CUGAUGAGGCCGAAAGGCCGAA AUCCAAU
282	1110	GGCUGAU CUGAUGAGGCCGAAAGGCCGAA ACAAUCC
285	1111	CAGGGCU CUGAUGAGGCCGAAAGGCCGAA AUGACAA
298	1112	GGUGCAA CUGAUGAGGCCGAAAGGCCGAA ACAGGCA
299	1113	AGGUGCA CUGAUGAGGCCGAAAGGCCGAA AACAGGC
300	1114	CAGGUGC CUGAUGAGGCCGAAAGGCCGAA AAACAGG
322	1115	CAAGUAA CUGAUGAGGCCGAAAGGCCGAA ACCAGGG
324	1116	CCCAAGU CUGAUGAGGCCGAAAGGCCGAA AGACCAG
325	1117	ACCCAAG CUGAUGAGGCCGAAAGGCCGAA AAGACCA
328	1118	UGGACCC CUGAUGAGGCCGAAAGGCCGAA AGUAAGA
333	1119	CAAUUUG CUGAUGAGGCCGAAAGGCCGAA ACCCAAG
339	1120	AGCCAAC CUGAUGAGGCCGAAAGGCCGAA AUUUGGA
342	1121	GAAAGCC CUGAUGAGGCCGAAAGGCCGAA ACAAUUU
347	1122	AAAGUGA CUGAUGAGGCCGAAAGGCCGAA AGCCAAC
348	1123	AAAAGUG CUGAUGAGGCCGAAAGGCCGAA AAGCCAA
349	1124	CAAAAGU CUGAUGAGGCCGAAAGGCCGAA AAAGCCA
353	1125	GGGUCAA CUGAUGAGGCCGAAAGGCCGAA AGUGAAA
354	1126	AGGGUCA CUGAUGAGGCCGAAAGGCCGAA AAGUGAA
355	1127	UAGGGUC CUGAUGAGGCCGAAAGGCCGAA AAAGUGA
362	1128	AGAUGCU CUGAUGAGGCCGAAAGGCCGAA AGGGUCA
368	1129	GGCUUCA CUGAUGAGGCCGAAAGGCCGAA AUGCUUA
404	1130	GGAUGGU CUGAUGAGGCCGAAAGGCCGAA AUGUUCC
410	1131	ACACUUG CUGAUGAGGCCGAAAGGCCGAA AUGGUGA
418	1132	AGGUAUG CUGAUGAGGCCGAAAGGCCGAA ACACUUG
422	1133	AUUGAGG CUGAUGAGGCCGAAAGGCCGAA AUGGACA
426	1134	AGAAAUU CUGAUGAGGCCGAAAGGCCGAA AGGUAUG
430	1135	UGAAAGA CUGAUGAGGCCGAAAGGCCGAA AUUGAGG
431	1136	CUGAAAG CUGAUGAGGCCGAAAGGCCGAA AAUUGAG
432	1137	GCUGAAA CUGAUGAGGCCGAAAGGCCGAA AAAUUGA
434	1138	GAGCUGA CUGAUGAGGCCGAAAGGCCGAA AGAAAUU
435	1139	AGAGCUG CUGAUGAGGCCGAAAGGCCGAA AAGAAAU
436	1140	AAGAGCU CUGAUGAGGCCGAAAGGCCGAA AAAGAAA
441	1141	GCACCAA CUGAUGAGGCCGAAAGGCCGAA AGCUGAA
443	1142	CAGCACC CUGAUGAGGCCGAAAGGCCGAA AGAGCUG
457	1143	UGAGAAA CUGAUGAGGCCGAAAGGCCGAA ACCAGCC
459	1144	AGUGAGA CUGAUGAGGCCGAAAGGCCGAA AGACCAG
460	1145	AAGUGAG CUGAUGAGGCCGAAAGGCCGAA AAGACCA
461	1146	GAAGUGA CUGAUGAGGCCGAAAGGCCGAA AAAGACC
463	1147	CAGAAGU CUGAUGAGGCCGAAAGGCCGAA AGAAAGA
467	1148	UGAACAG CUGAUGAGGCCGAAAGGCCGAA AGUGAGA
468	1149	CUGAACA CUGAUGAGGCCGAAAGGCCGAA AAGUGAG
472	1150	ACACCUG CUGAUGAGGCCGAAAGGCCGAA ACAGAAG
473	1151	AACACCU CUGAUGAGGCCGAAAGGCCGAA AACAGAA
480	1152	CGUGGAU CUGAUGAGGCCGAAAGGCCGAA ACACCUG
481	1153	ACGUGGA CUGAUGAGGCCGAAAGGCCGAA AACACCU
483	1154	UCAGGUG CUGAUGAGGCCGAAAGGCCGAA AUAACAC
521	1155	ACCACAG CUGAUGAGGCCGAAAGGCCGAA ACAGCGU
529	1156	ACAUUGU CUGAUGAGGCCGAAAGGCCGAA ACCACAG
537	1157	CAACAGA CUGAUGAGGCCGAAAGGCCGAA ACAUUGU
538	1158	UCAACAG CUGAUGAGGCCGAAAGGCCGAA AACAUUG
539	1159	UUCAACA CUGAUGAGGCCGAAAGGCCGAA AAACAUU
543	1160	GCUCUUC CUGAUGAGGCCGAAAGGCCGAA ACAGAAA
562	1161	UAGAUGC CUGAUGAGGCCGAAAGGCCGAA AGUUUGU
567	1162	GCCAGUA CUGAUGAGGCCGAAAGGCCGAA AUGCGAG
569	1163	UUGCCAG CUGAUGAGGCCGAAAGGCCGAA AGAUGCG
601	1164	GACAUCA CUGAUGAGGCCGAAAGGCCGAA AGUCAGC
608	1165	GUCCCCA CUGAUGAGGCCGAAAGGCCGAA ACAUCAU
622	1166	GGCCAUA CUGAUGAGGCCGAAAGGCCGAA AUUCAUG
624	1167	CGGGCCA CUGAUGAGGCCGAAAGGCCGAA AUAUUCA
635	1168	GUUCUUG CUGAUGAGGCCGAAAGGCCGAA ACUCGGG
651	1169	UAUCAAA CUGAUGAGGCCGAAAGGCCGAA AUGGUCC
653	1170	GAUAUCA CUGAUGAGGCCGAAAGGCCGAA AGAUGGU
654	1171	UGAUAUC CUGAUGAGGCCGAAAGGCCGAA AAGAUGG
658	1172	UUAGUGA CUGAUGAGGCCGAAAGGCCGAA AUCAAAG
660	1173	UAUUAGU CUGAUGAGGCCGAAAGGCCGAA AUAUCAA
664	1174	AGGUUAU CUGAUGAGGCCGAAAGGCCGAA AGUGAUA
667	1175	GAGAGGU CUGAUGAGGCCGAAAGGCCGAA AUUAGUG
672	1176	CAAUGGA CUGAUGAGGCCGAAAGGCCGAA AGGUUAU
674	1177	CACAAUG CUGAUGAGGCCGAAAGGCCGAA AGAGGUU
678	1178	GGAUCAC CUGAUGAGGCCGAAAGGCCGAA AUGGAGA
684	1179	GAGCCAG CUGAUGAGGCCGAAAGGCCGAA AUCACAA
691	1180	GGGCGCA CUGAUGAGGCCGAAAGGCCGAA AGCCAGG
701	1181	CUCGUCA CUGAUGAGGCCGAAAGGCCGAA AUGGGCG
716	1182	ACACUCG CUGAUGAGGCCGAAAGGCCGAA AUGUGCC
726	1183	UCAGAAC CUGAUGAGGCCGAAAGGCCGAA ACACACU
729	1184	ACUUCAG CUGAUGAGGCCGAAAGGCCGAA ACAACAC
730	1185	UACUUCA CUGAUGAGGCCGAAAGGCCGAA AACAACA
737	1186	UUUUUCA CUGAUGAGGCCGAAAGGCCGAA ACUUCAG
751	1187	CGCUUGA CUGAUGAGGCCGAAAGGCCGAA AGCGUCU
752	1188	CCGCUUG CUGAUGAGGCCGAAAGGCCGAA AAGCGUC
753	1189	CCCGCUU CUGAUGAGGCCGAAAGGCCGAA AAAGCGU
782	1190	GACUGAU CUGAUGAGGCCGAAAGGCCGAA ACGUCAC
783	1191	UGACUGA CUGAUGAGGCCGAAAGGCCGAA AACGUCA
785	1192	UUUGACU CUGAUGAGCCCGAAAGGCCGAA AUAACGU
789	1193	CAGCUUU CUGAUGAGGCCGAAAGGCCGAA ACUGAUA
800	1194	UGUAGGG CUGAUGAGGCCGAAAGGCCGAA AGUCAGC
801	1195	GUGUAGG CUGAUGAGGCCGAAAGGCCGAA AAGUCAG
805	1196	CUAGGUG CUGAUGAGGCCGAAAGGCCGAA AGGGAAG
811	1197	GAUAUAC CUGAUGAGGCCGAAAGGCCGAA AGGUGUA
814	1198	UCAGAUA CUGAUGAGGCCGAAAGGCCGAA ACUAGGU
816	1199	AGUCAGA CUGAUGAGGCCGAAAGGCCGAA AUACUAG
818	1200	AAAGUCA CUGAUGAGGCCGAAAGGCCGAA AUAUACU
824	1201	AAUUUCA CUGAUGAGGCCGAAAGGCCGAA AGUCAGA
825	1202	GAAUUUC CUGAUGAGGCCGAAAGGCCGAA AAGUCAG
831	1203	AAGUUGG CUGAUGAGGCCGAAAGGCCGAA AUUUCAA
832	1204	GAAGUUG CUGAUGAGGCCGAAAGGCCGAA AAUUUCA
838	1205	AUAUUAG CUGAUGAGGCCGAAAGGCCGAA AGUUGGA
839	1206	AAUAUUA CUGAUGAGGCCGAAAGGCCGAA AAGUUGG
841	1207	CUAAUAU CUGAUGAGGCCGAAAGGCCGAA AGAAGUU
844	1208	CUUCUAA CUGAUGAGGCCGAAAGGCCGAA AUUAGAA
846	1209	UCCUUCU CUGAUGAGGCCGAAAGGCCGAA AUAUUAG
847	1210	AUCCUUC CUGAUGAGGCCGAAAGGCCGAA AAUAUUA
855	1211	AGCAAAU CUGAUGAGGCCGAAAGGCCGAA AUCCUUC
858	1212	UUGAGCA CUGAUGAGGCCGAAAGGCCGAA AUUAUCC
859	1213	GUUGAGC CUGAUGAGGCCGAAAGGCCGAA AAUUAUC
863	1214	AGAGGUU CUGAUGAGGCCGAAAGGCCGAA AGCAAAU
869	1215	ACCUCCA CUGAUGAGGCCGAAAGGCCGAA AGGUUGA
877	1216	UCUGGAA CUGAUGAGGCCGAAAGGCCGAA ACCUCCA
878	1217	CUCUGGA CUGAUGAGGCCGAAAGGCCGAA AACCUCC
879	1218	GCUCUGG CUGAUGAGGCCGAAAGGCCGAA AAACCUC
880	1219	GGCUCUG CUGAUGAGGCCGAAAGGCCGAA AAAACCU
889	1220	GAGAGGU CUGAUGAGGCCGAAAGGCCGAA AGGCUCU
894	1221	ACCAGGA CUGAUGAGGCCGAAAGGCCGAA AGGUGAG
896	1222	CAACCAG CUGAUGAGGCCGAAAGGCCGAA AGAGGUG
902	1223	AUUUUCC CUGAUGAGGCCGAAAGGCCGAA ACCAGGA
920	1224	GGCAUUU CUGAUGAGGCCGAAAGGCCGAA AUUCUUC
921	1225	UGGCAUU CUGAUGAGGCCGAAAGGCCGAA AAUUCUU
930	1226	UUGUGUU CUGAUGAGGCCGAAAGGCCGAA AUGGCAU
942	1227	CUUGGGA CUGAUGAGGCCGAAAGGCCGAA ACUGUUG
943	1228	UCUUGGG CUGAUGAGGCCGAAAGGCCGAA AACUGUU
944	1229	AUCUUGG CUGAUGAGGCCGAAAGGCCGAA AAACUGU
952	1230	GUUUCAG CUGAUGAGGCCGAAAGGCCGAA AUCUUGG
966	1231	CAGCAUA CUGAUGAGGCCGAAAGGCCGAA AGCUCAG
968	1232	AACAGCA CUGAUGAGGCCGAAAGGCCGAA AGAGCUC
975	1233	UGCUGCU CUGAUGAGGCCGAAAGGCCGAA ACAGCAU
976	1234	UUGCUGC CUGAUGAGGCCGAAAGGCCGAA AACAGCA
991	1235	AUAUUGA CUGAUGAGGCCGAAAGGCCGAA AUCCAGU
992	1236	CAUAUUG CUGAUGAGGCCGAAAGGCCGAA AAUCCAG
993	1237	UCAUAUU CUGAUGAGGCCGAAAGGCCGAA AAAUCCA
997	1238	GUUGUCA CUGAUGAGGCCGAAAGGCCGAA AUUGAAA
1016	1239	ACACAUG CUGAUGAGGCCGAAAGGCCGAA AGCUGUG
1017	1240	GACACAU CUGAUGAGGCCGAAAGGCCGAA AAGCUGU
1024	1241	UUGAUGA CUGAUGAGGCCGAAAGGCCGAA ACACAUG
1026	1242	ACUUGAU CUGAUGAGGCCGAAAGGCCGAA AGACACA
1029	1243	CAUACUU CUGAUGAGGCCGAAAGGCCGAA AUGAGAC
1034	1244	AUGUCCA CUGAUGAGGCCGAAAGGCCGAA ACUUGAU
1042	1245	ACUCUUA CUGAUGAGGCCGAAAGGCCGAA AUGUCCA
1043	1246	CACUCUU CUGAUGAGGCCGAAAGGCCGAA AAUGUCC
1044	1247	UCACUCU CUGAUGAGGCCGAAAGGCCGAA AAAUGUC
1054	1248	AAGGUCU CUGAUGAGGCCGAAAGGCCGAA AUUCACU
1061	1249	CCAGUUG CUGAUGAGGCCGAAAGGCCGAA AGGUCUG
1062	1250	UCCAGUU CUGAUGAGGCCGAAAGGCCGAA AAGGUCU
1072	1251	UUGGUUG CUGAUGAGGCCGAAAGGCCGAA AUUCCAG
1090	1252	UCAGGAA CUGAUGAGGCCGAAAGGCCGAA AUGCUCU
1091	1253	AUCAGGA CUGAUGAGGCCGAAAGGCCGAA AAUGCUC
1092	1254	UAUCAGG CUGAUGAGGCCGAAAGGCCGAA AAAUGCU
1093	1255	UUAUCAG CUGAUGAGGCCGAAAGGCCGAA AAAAUGC
1099	1256	AGCAGGU CUGAUGAGGCCGAAAGGCCGAA AUCAGGA
1107	1257	AGGAUGG CUGAUGAGGCCGAAAGGCCGAA AGCAGGU
1112	1258	GGCCCAG CUGAUGAGGCCGAAAGGCCGAA AUGGGAG
1122	1259	UUAAGGU CUGAUGAGGCCGAAAGGCCGAA AUGGCCC
1123	1260	AUUAAGG CUGAUGAGGCCGAAAGGCCGAA AAUGGCC
1127	1261	UGAGAUU CUGAUGAGGCCGAAAGGCCGAA AGGUAAU
1128	1262	CUGAGAU CUGAUGAGGCCGAAAGGCCGAA AAGGUAA
1131	1263	UUACUGA CUGAUGAGGCCGAAAGGCCGAA AUUAAGG
1133	1264	AUUUACU CUGAUGAGGCCGAAAGGCCGAA AGAUUAA
1137	1265	UUCCAUU CUGAUGAGGCCGAAAGGCCGAA ACUGAGA
1146	1266	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AUUCCAU
1147	1267	AUCACAA CUGAUGAGGCCGAAAGGCCGAA AAUUCCA
1148	1268	UAUCACA CUGAUGAGGCCGAAAGGCCGAA AAAUUCC
1149	1269	AUAUCAC CUGAUGAGGCCGAAAGGCCGAA AAAAUUC
1155	1270	GGCAGCA CUGAUGAGGCCGAAAGGCCGAA AUCACAA
1169	1271	AAAGCAG CUGAUGAGGCCGAAAGGCCGAA AGGUCAG
1175	1272	UGGGGCA CUGAUGAGGCCGAAAGGCCGAA AGCAGUA
1176	1273	UUGGGGC CUGAUGAGGCCGAAAGGCCGAA AAGCAGU
1214	1274	CCUUCUC CUGAUGAGGCCGAAAGGCCGAA AUCUCUC
1230	1275	CAGGGCG CUGAUGAGGCCGAAAGGCCGAA ACACUUU
1239	1276	ACUGUUA CUGAUGAGGCCGAAAGGCCGAA ACAGGGC
1241	1277	ACACUGU CUGAUGAGGCCGAAAGGCCGAA AUACAGG
1249	1278	UUCUGCG CUGAUGAGGCCGAAAGGCCGAA ACACUGU
1275	1279	ACCUUCA CUGAUGAGGCCGAAAGGCCGAA AUCUUUU
1283	1280	CGGAGGC CUGAUGAGGCCGAAAGGCCGAA ACCUUCA
1288	1281	GAUGACG CUGAUGAGGCCGAAAGGCCGAA AGGCUAC
1292	1282	AAGAGAU CUGAUGAGGCCGAAAGGCCGAA ACGGAGG
1295	1283	CAGAAGA CUGAUGAGGCCGAAAGGCCGAA AUGACGG
1297	1284	CCCAGAA CUGAUGAGGCCGAAAGGCCGAA AGAUGAC
1299	1285	AUCCCAG CUGAUGAGGCCGAAAGGCCGAA AGAGAUG
1300	1286	UAUCCCA CUGAUGAGGCCGAAAGGCCGAA AAGAGAU
1307	1287	AUCCAUG CUGAUGAGGCCGAAAGGCCGAA AUCCCAG
1315	1288	UCCCCAC CUGAUGAGGCCGAAAGGCCGAA AUCCAUG
1324	1289	GCCUCAU CUGAUGAGGCCGAAAGGCCGAA AUCCCCA
1334	1290	AGGGAAG CUGAUGAGGCCGAAAGGCCGAA AUGCCUC
1335	1291	AAGGGAA CUGAUGAGGCCGAAAGGCCGAA AAUGCCU
1337	1292	UUAAGGG CUGAUGAGGCCGAAAGGCCGAA AGAAUGC
1338	1293	GUUAAGG CUGAUGAGGCCGAAAGGCCGAA AAGAAUG
1342	1294	AUUUGUU CUGAUGAGGCCGAAAGGCCGAA AGGGAAG
1343	1295	AAUUUGU CUGAUGAGGCCGAAAGGCCGAA AAGGGAA
1350	1296	CAGCUUA CUGAUGAGGCCGAAAGGCCGAA AUUUGUU
1351	1297	ACAGCUU CUGAUGAGGCCGAAAGGCCGAA AAUUUGU
1352	1298	AACAGCU CUGAUGAGGCCGAAAGGCCGAA AAAUUUG
1359	1299	UGGGUAA CUGAUGAGGCCGAAAGGCCGAA ACAGCUU
1360	1300	GUGGGUA CUGAUGAGGCCGAAAGGCCGAA AACAGCU
1361	1301	AGUGGGU CUGAUGAGGCCGAAAGGCCGAA AAACAGC
1362	1302	UAGUGGG CUGAUGAGGCCGAAAGGCCGAA AAAACAG
1369	1303	GGUGAGG CUGAUGAGGCCGAAAGGCCGAA AGUGGGU
1373	1304	AGAAGGU CUGAUGAGGCCGAAAGGCCGAA AGGUAGU
1378	1305	UUUUAAG CUGAUGAGGCCGAAAGGCCGAA AGGUGAG
1379	1306	UUUUUAA CUGAUGAGGCCGAAAGGCCGAA AAGGUGA
1381	1307	GGUUUUU CUGAUGAGGCCGAAAGGCCGAA AGAAGGU
1382	1308	AGGUUUU CUGAUGAGGCCGAAAGGCCGAA AAGAAGG
1390	1309	UCUGAAA CUGAUGAGGCCGAAAGGCCGAA AGGUUUU
1392	1310	AAUCUGA CUGAUGAGGCCGAAAGGCCGAA AGAGGUU
1393	1311	UAAUCUG CUGAUGAGGCCGAAAGGCCGAA AAGAGGU
1394	1312	UUAAUCU CUGAUGAGGCCGAAAGGCCGAA AAAGAGG
1399	1313	UCAGCUU CUGAUGAGGCCGAAAGGCCGAA AUCUGAA
1400	1314	UUCAGCU CUGAUGAGGCCGAAAGGCCGAA AAUCUGA
1412	1315	AUCUUGU CUGAUGAGGCCGAAAGGCCGAA ACUGUUC
1413	1316	CAUCUUG CUGAUGAGGCCGAAAGGCCGAA AACUGUU
1429	1317	GGAGAGG CUGAUGAGGCCGAAAGGCCGAA AUGCCAG
1433	1318	GAAAGGA CUGAUGAGGCCGAAAGGCCGAA AGGGAUG
1435	1319	GAGAAAG CUGAUGAGGCCGAAAGGCCGAA AGAGGGA
1438	1320	GGGGAGA CUGAUGAGGCCGAAAGGCCGAA AGGAGAG
1439	1321	UGGGGAG CUGAUGAGGCCGAAAGGCCGAA AAGGAGA
1440	1322	AUGGGGA CUGAUGAGGCCGAAAGGCCGAA AAAGGAG
1442	1323	AUAUGGG CUGAUGAGGCCGAAAGGCCGAA AGAAAGG
1448	1324	AAUUGCA CUGAUGAGGCCGAAAGGCCGAA AUGGGGA
1455	1325	UUAAGCA CUGAUGAGGCCGAAAGGCCGAA AUUGCAU
1456	1326	AUUAAGC CUGAUGAGGCCGAAAGGCCGAA AAUUGCA
1460	1327	UUACAUU CUGAUGAGGCCGAAAGGCCGAA AGCAAAU
1461	1328	GUUACAU CUGAUGAGGCCGAAAGGCCGAA AAGCAAA
1466	1329	AAGAGGU CUGAUGAGGCCGAAAGGCCGAA ACAUUAA
1471	1330	AAAAGAA CUGAUGAGGCCGAAAGGCCGAA AGGUUAC
1473	1331	GCAAAAG CUGAUGAGGCCGAAAGGCCGAA AGAGGUU
1474	1332	GGCAAAA CUGAUGAGGCCGAAAGGCCGAA AAGAGGU
1476	1333	AUGGCAA CUGAUGAGGCCGAAAGGCCGAA AGAAGAG
1477	1334	CAUGGCA CUGAUGAGGCCGAAAGGCCGAA AAGAAGA
1478	1335	ACAUGGC CUGAUGAGGCCGAAAGGCCGAA AAAGAAG
1486	1336	GAAUGGA CUGAUGAGGCCGAAAGGCCGAA ACAUGGC
1487	1337	AGAAUGG CUGAUGAGGCCGAAAGGCCGAA AACAUGG
1488	1338	CAGAAUG CUGAUGAGGCCGAAAGGCCGAA AAACAUG
1492	1339	AUGGCAG CUGAUGAGGCCGAAAGGCCGAA AUGGAAA
1493	1340	GAUGGCA CUGAUGAGGCCGAAAGGCCGAA AAUGGAA
1500	1341	AAUUCAA CUGAUGAGGCCGAAAGGCCGAA AUGGCAG
1502	1342	ACAAUUC CUGAUGAGGCCGAAAGGCCGAA AGAUGGC
1507	1343	ACAAGAC CUGAUGAGGCCGAAAGGCCGAA AUUCAAG
1510	1344	CUGACAA CUGAUGAGGCCGAAAGGCCGAA ACAAUUC
1512	1345	GGCUGAC CUGAUGAGGCCGAAAGGCCGAA AGACAAU
1515	1346	AUUGGCU CUGAUGAGGCCGAAAGGCCGAA ACAAGAC
1523	1347	GAUAAUG CUGAUGAGGCCGAAAGGCCGAA AUUGGCU
1524	1348	AGAUAAU CUGAUGAGGCCGAAAGGCCGAA AAUUGGC
1527	1349	AAUAGAU CUGAUGAGGCCGAAAGGCCGAA AUGAAUU
1528	1350	UAAUAGA CUGAUGAGGCCGAAAGGCCGAA AAUGAAU
1530	1351	UUUAAUA CUGAUGAGGCCGAAAGGCCGAA AUAAUGA
1532	1352	UGUUUAA CUGAUGAGGCCGAAAGGCCGAA AGAUAAU
1534	1353	AGUGUUU CUGAUGAGGCCGAAAGGCCGAA AUAGAUA
1535	1354	UAGUGUU CUGAUGAGGCCGAAAGGCCGAA AAUAGAU
1542	1355	CUCAAAU CUGAUGAGGCCGAAAGGCCGAA AGUGUUU

[0088]

TABLE IV
Mouse B7-1 Hammerhead Ribozyme Target Sequences
nt.	SEQ ID	HH Target
Position	NO	Sequence
8	300	GaGUuUU a UACcUcA
10	301	guUuuAU A CCUCAAU
10	301	GUuUUaU a CCUCAAU
14	302	uAUaCCU c aAUAGAC
18	303	CcucAAU A gaCUCUu
18	303	CCUCaaU a gaCUCUU
18	303	CcUcAAU a GaCUcuU
23	304	AuaGaCU c uUACuaG
25	305	AGACuCU U aCuAGuu
26	306	GACuCUU a CuAGuuu
29	307	UCUUACU a GuuUCuc
29	307	UcUuACU a gUuuCuC
29	307	UCUUaCU a guUUCUc
29	307	UCuuaCU a gUUUCUC
34	308	CUaGUuU c UCUuuuU
34	308	CUAGUuU c UCUuuuU
34	308	cUAgUuU c uCuUuUU
40	309	ucuCUuU U UCAGgUU
41	310	cUCUuUU u caGGuUg
41	310	cuCUuUU U CAGgUUg
42	311	uCUuUUU C AGgUUgu
56	312	UGAAACU c AAcCuuC
56	312	UGAAAcU C aAcCUUC
62	313	uCAACCU U caaAGAC
62	313	UCaAcCU U CaAAgAc
62	313	UCAACCU u caaAGac
63	314	CAACCUU c aaAGACa
73	315	aGAcAcU c UGuUCcA
77	316	acUCUgU u cCAuUUC
78	317	CUCUGUU C CauUUCU
83	318	UucCAuU U CUGUggA
93	319	GUggACU A AuAGgAu
93	319	gUgGacU a AUAGgaU
93	319	gUGgAcU a AuAGGAU
96	320	GAcuAAU a GGAUcaU
96	320	gacuAAU a gGAuCaU
101	321	AUaGGAU c aUCuUuA
104	322	GGAuCAU C uuuAgCa
104	322	GGAuCAU C UUUagcA
106	323	AuCAUCU U UagcAUC
107	324	UcAuCuU u AGCAUCU
107	324	uCaUCUU u AgcAuCU
241	325	AAAgcAU C UGAAGcU
249	326	UGAAgcU A UGGCuuG
264	327	CAAuUgU c AGuUGaU
287	328	CAcCaCU c CUcaagU
295	329	CUCaAgU u UCcaUGU
295	329	cuCAaGU U UCCAUgu
296	330	uCAAgUU u ccAUgUc
297	331	CAAGUuU C CAUguCc
297	331	CAaGuuU c cAUGuCC
314	332	GGCUcaU u cUUCUCu
314	332	GgcuCAU U CUUCuCU
315	333	GcuCAUU c UuCUcuU
315	333	gcuCAUU C UUCuCUU
317	334	uCAUUCU U CuCUUug
318	335	CAUUCUU C uCUUugu
318	335	CAUuCuU C UCuUUgu
320	336	uUCUUCU c uUUGuGC
320	336	UUCuuCU C UUuGUGC
322	337	CuuCUCU U uGUGCUG
322	337	CUucuCU u UgUGCUG
323	338	UUcuCUU u gUGcugC
336	339	gcUGAUU c GUCuUUC
341	340	uUCGuCU u UCacAAG
341	340	UUCgucU u UcAcAAG
342	341	UcGUCUU U CaCAagU
343	342	cgucUuU C AcAAGUG
343	342	cGuCuUU c AcaAGUG
352	343	caAGUGU C uuCAGAu
355	344	gUgUcUU C AGaUGUU
382	345	UCcaAGU c AgUGaAA
408	346	gCUGCcU U GCCguuA
414	347	UUGccgU U aCAACUc
414	347	UUgCCgU u ACAAcUc
421	348	UaCAAcU c uCcUcAU
426	349	CUCuCCU c aUgAAgA
439	350	GaUGAgU C UGAaGaC
452	351	acCGaAU C UACUGGC
454	352	CGaAUCU A CUGGCAA
484	353	GuGCUgU C UGucaUU
484	353	GUgCUGU c UguCAuU
488	354	ugUcUGU C AUUGCUg
503	355	gGAAacU A aAAGuGu
503	355	ggAAAcU a AAagUGU
520	356	CCCGAGU A uAAGAAC
535	357	cGGAcUU U aUaUGAc
536	358	GGAcUUU a UaUGAcA
538	359	AcUuUAU a UGACaac
553	360	acuACCU a cUCUcUU
553	360	AcUaCcU a cUCUcUU
760	361	gGGgGUU u cCCAaag
760	361	GGgGGUU U cCCAaAG
761	362	GgGGUUU c CCAaAGC
771	363	aAAgccU C GCuUCUC
771	363	AaAGCCU C gCuUCUC
776	364	CUCgCUU C UcUUggu
776	364	CUCgCuU C UCuUGGU
778	365	CgCuUCU C uUGGUUG
784	366	UCuUGGU U GGAAAAU
803	367	GAGaaUU A CCugGcA
803	367	gAGAAUU A ccUGgCA
803	367	gagAaUU a CCUGgcA
812	368	cUGgCAU c AAuACgA
812	368	CUGGCAU C aAuaCgA
816	369	caUCAAU A cGACAAu
816	369	cAUCaAU a cgACAaU
824	370	CgACAaU U UCCCAgG
825	371	gACAaUU U CCCAgGA
826	372	ACAaUUU C CCAgGAU
834	373	CCAgGAU C CUGAAuC
841	374	CcUGaaU C ugAAUUG
841	374	cCUGAaU c UGAAuUg
850	375	gAAuUGU A CaCCaUu
869	376	gccAaCU a gAUuUCA
869	376	GCCAaCU a GAuUUca
869	376	GCCAAcU a gaUuUCa
873	377	acUaGAU u UCAaUAc
873	377	ACUaGAU U UCAAUAc
874	378	CUaGAUU U CAAUAcG
875	379	UaGAUUU C AAUAcGA
885	380	UAcgACU C gcAACCa
899	381	ACACCaU u aAgUgUC
899	381	ACAcCaU u aAGUGUC
906	382	UaaGUGU c UcaUuAA
906	382	uAaGUGU C UCAUuAA
908	383	aGUGUCU C AUuAAaU
911	384	GUCUCAU u AAaUAUG
916	385	AUuAaaU a UGGaGAu
916	385	AUuAAaU A UGGAgAU
943	386	gAGgaCU U CAcCUGG
944	387	AGgaCUU C ACCUGGg
1001	388	UGCUcUU u GggGCAg
1034	389	CAGucGU c gUCauCG
1037	390	UcGUCgU C AuCguUG
1043	391	uCAUCgU U GucAUCA
1046	392	ucgUUGU c AuCAUCA
1049	393	uUguCaU c AuCAAAU
1060	394	aAAUGcU U CUGUaag
1060	394	AAaUgCU u cUgUaAG
1475	395	gCCUAGU c UuaCUGc
1477	396	CUaGUCU U ACUgcaa
1487	397	ugCAaCU U gAUaUGU
1491	398	ACuUGAU a UGUCAUg
1491	398	aCUUgaU a UGuCAUG
1505	399	gUUUGgU U ggUGUcu
1530	400	uGCCcUU U uCUgAAg
1531	401	GCccUUU u CUGAagA
1532	402	CcCuUuU C UGAAGAg
1532	402	CcCuuuU C UGAaGAG
1644	403	CUaUGGU u gggAUGU
1652	404	ggGAuGU a AaAAcGG
1652	404	GgGAugU a aAaAcGG
1670	405	aUaAUAU a AaUAuUA
1674	406	uAuAAAU a UuAaaUa
1676	407	UaAaUAU u aAaUAAA
1677	408	AAauAUU a AAuaAAA
1677	408	AaaUAUU A AAuAaaA
1694	409	AGagUaU u gAGcAAA
108	410	CaUcUUU a GCAuCUG
108	410	CAUcUUU a gcaUCUG
131	411	aUGCCAU C caGgcUU
142	412	gCUuCUU u uUCuaCA
142	412	gCuUCUU U UUcUaCa
143	413	CUuCUUU u UCuaCAU
143	413	CuUcUuU u uCuAcAU
143	413	CUUCUUU U uCuAcaU
143	413	cUUCuUU u UCUAcau
144	414	UuCuUuU U cUaCAuC
144	414	UuCuuuU u cUAcAUC
144	414	UUCuuUU u cuaCAUC
147	415	uUUUuCU a cAuCUCU
153	416	uAcAuCU C ugUUUCU
165	417	uCUCgAU U UuUgUgA
165	417	uCUcgAU u UuuGUgA
165	417	ucucgAU U UUUGUGA
166	418	CUCgAUU U uUgUgAG
167	419	uCgAUuU U UGUGaGc
167	419	ucGauUU U UGUgAgC
167	419	UCgAUUU u UgUgAGC
168	420	cGAUUuU u gUgAGCC
168	420	cgAUUUU U GUGAgcc
197	421	GCUccAU u GgCUCUA
202	422	aUUGGCU c UagaUuc
208	423	UCuAgAU U ccUGGCU
216	424	CCUGGCU u UcCcCau
217	425	cUGGCUU U CcCcaUc
217	425	cUgGCuU u CccCAUC
217	425	CUGGCuU u CCcCauC
218	426	UGGcuUU C ccCaUCA
218	426	UGGCUUU C cCcaUca
218	426	UGgCUUU c cCcaUCA
218	426	ugGcUUU c CCCAucA
224	427	UCcCCAU c aUGuUCu
224	427	UccCCAU c aUGuucU
230	428	UCAugUU C UccAAAg
232	429	AuGUUcU C CAaAGCa
232	429	AUGuUcU c caaAGCA
232	429	AugUUCU c cAAAgCa
241	325	AAAGcAU c UgAAGcu
241	325	aAAGCAU C UGAAGCu
556	430	ACCUACU c uCUuAuC
556	430	AcCuAcU c ucUUAUC
560	431	AcUcUCU U aUCAuCC
561	432	cUCuCUU a UcAuCCU
561	432	cuCUcuU a uCAUCCU
561	432	CUCUCuU a UCauCCu
566	433	UUaUcAU C CUGGgcC
566	433	uUauCAU C CUGGGCC
581	434	UGGuCcU U UcAGAcc
583	435	gucCUUU C AgaCcGG
583	435	GuCcUUU c AGAcCGg
598	436	GGCACAU A CagcUGU
608	437	gcUGUGU c GUUCaaA
611	438	GUGUcgU u CAaaaGA
611	438	GUGUcGU U CaaAAGa
612	439	UGUcGUU C aaAAGaA
641	440	aUGaAGU u aaACaCU
649	441	AAAcaCU U GGCUUUa
649	441	AaaCAcU U gGCUUuA
655	442	UUggcuU u AGUAAAg
656	443	UGgcUUU a GUAAAgu
659	444	CuUuaGU A AAGUugu
664	445	GUaAaGU U gUCcaUC
667	446	AaGUUgU C caUCAAA
671	447	UgUCcaU C AAAGCUG
682	448	gCUgAcU u CuCuACC
682	448	GCUGACU U CuCUACc
682	448	GCUGacU U cuCuACc
683	449	CUGACUU C uCUACcC
683	449	CUGACUU c ucuAccC
685	450	gACUuCU c UaCCCCc
685	450	gaCUucU c UACCCcC
687	451	CUUCuCU A CcCCcAa
698	452	ccAACAU a ACUGagu
698	452	CCaacAU A ACuGaGU
718	453	AAcCCaU c UGcAgAc
718	453	aaCCCAU C UGCAgac
729	454	AGACacU A AaAgGAu
729	454	agAcAcU A aAAGGAU
729	454	agACAcU a AaAgGAU
737	455	aAAGGAU u AccUGCU
737	455	aAAGgAU U AccUGCu
737	455	aaagGAU u ACCUGCU
745	456	aCCUGcU U UGCuuCc
745	456	accUGcU u UGCUuCC
759	457	cGggGgU U uCCCAAA
759	457	cGgGGGU u UcCcAaa
759	457	cGGgGGU U UcCCAaA
760	361	GggGgUU u CCCAAAG
1060	394	aAAUgcU u cUGUaAG
1060	394	AAAugCU u cUgUaAG
1061	458	AAUGcUU C UGUaagc
1080	459	AagcugU u UCAGAAG
1080	459	AAGCUGU U UcAgaag
1081	460	AgcuGUU u CAgaAga
1121	461	acAGcCU U ACCuUcg
1121	461	AcAgCCU u aCCuUcG
1121	461	ACagCCU u ACCUUCg
1122	462	CaGcCuU a cCUUCgG
1126	463	CUuACCU u CgGgccU
1127	464	UUaCcUU c ggGcCUG
1127	464	UuACcUU c GggCCUg
1144	465	GaagCAU U AgCUgAA
1144	465	gaAGcaU u AGCUGAA
1145	466	aAgcAUU a GCUgAAC
1160	467	AGAcCgU c UUCCUuu
1162	468	ACCgUCU u CcUUuaG
1163	469	ccGUCUU c CUUuaGU
1167	470	cUUCcUU u AGuUCUU
1177	471	uUCUUCU c UguCCAU
1181	472	UCuCugU C CAuGUGg
1181	472	ucUCUGU c CAuGUGg
1192	473	gUGGGAU A CAUGGua
1199	474	aCaUGGU a UUAugUG
1201	475	AuGgUaU u aUGUGGc
1210	476	ugUGGcU C aUGaGGu
1210	476	UGuGGcU C AUGAGGu
1223	477	GUacAAU c UUUCUUu
1225	478	ACAAUcU U UCUuUca
1225	478	ACAAuCU u uCuUucA
1226	479	caAuCUU u cUuUCAG
1227	480	aAucUUU C uUUCAGC
1227	480	AAucuuU C UUUCAGc
1227	480	AAUCUuU C uUUcaGC
1229	481	ucUUUCU U UCAGCaC
1230	482	cUUUCUU U CAGCaCc
1252	483	cUgAUCU u UcggACA
1274	484	acaAGAU a gAGuUaA
1310	485	UGAgGaU u uCuUuCc
1312	486	aGgAUUU c UuUcCAu
1314	487	gAUUUcU u UcCAuCA
1316	488	UUUcUuU c CAuCAgG
1320	489	UUUcCaU C AGgAAGC
1320	489	UUUCcaU c aggaAGC
1339	490	GgCAagU u UgCUGGG
1355	491	cUuUgAU U GCUUgAU
1437	492	gUGguaU A aGAAAAA
1437	492	gUggUAU a AGAAaaA

[0089]

TABLE V
Mouse B7-1 Hammerhead Ribozyme Sequences
nt.	SEQ ID
Position	NO	HH Ribozyme Sequences
8	1439	UGAGGUA CUGAUGAGGCCGAAAGGCCGAA AAAACUC
10	1440	AUUGAGG CUGAUGAGGCCGAAAGGCCGAA AUAAAAC
10	1440	AUUGAGG CUGAUGAGGCCGAAAGGCCGAA AUAAAAC
14	1441	GUCUAUU CUGAUGAGGCCGAAAGGCCGAA AGGUAUA
18	1442	AAGAGUC CUGAUGAGGCCGAAAGGCCGAA AUUGAGG
18	1442	AAGAGUC CUGAUGAGGCCGAAAGGCCGAA AUUGAGG
18	1442	AAGAGUC CUGAUGAGGCCGAAAGGCCGAA AUUGAGG
23	1443	CUAGUAA CUGAUGAGGCCGAAAGGCCGAA AGUCUAU
25	1444	AACUAGU CUGAUGAGGCCGAAAGGCCGAA AGAGUCU
26	1445	AAACUAG CUGAUGAGGCCGAAAGGCCGAA AAGAGUC
29	1446	GAGAAAC CUGAUGAGGCCGAAAGGCCGAA AGUAAGA
29	1446	GAGAAAC CUGAUGAGGCCGAAAGGCCGAA AGUAAGA
29	1446	GAGAAAC CUGAUGAGGCCGAAAGGCCGAA AGUAAGA
29	1446	GAGAAAC CUGAUGAGGCCGAAAGGCCGAA AGUAAGA
34	1447	AAAAAGA CUGAUGAGGCCGAAAGGCCGAA AAACUAG
34	1447	AAAAAGA CUGAUGAGGCCGAAAGGCCGAA AAACUAG
34	1447	AAAAAGA CUGAUGAGGCCGAAAGGCCGAA AAACUAG
40	1448	AACCUGA CUGAUGAGGCCGAAAGGCCGAA AAAGAGA
41	1449	CAACCUG CUGAUGAGGCCGAAAGGCCGAA AAAAGAG
41	1449	CAACCUG CUGAUGAGGCCGAAAGGCCGAA AAAAGAG
42	1450	ACAACCU CUGAUGAGGCCGAAAGGCCGAA AAAAAGA
56	1451	GAAGGUU CUGAUGAGGCCGAAAGGCCGAA AGUUUCA
56	1451	GAAGGUU CUGAUGAGGCCGAAAGGCCGAA AGUUUCA
62	1452	GUCUUUG CUGAUGAGGCCGAAAGGCCGAA AGGUUGA
62	1452	GUCUUUG CUGAUGAGGCCGAAAGGCCGAA AGGUUGA
62	1452	GUCUUUG CUGAUGAGGCCGAAAGGCCGAA AGGUUGA
63	1453	UGUCUUU CUGAUGAGGCCGAAAGGCCGAA AAGGUUG
73	1454	UGGAACA CUGAUGAGGCCGAAAGGCCGAA AGUGUCU
77	1455	GAAAUGG CUGAUGAGGCCGAAAGGCCGAA ACAGAGU
78	1456	AGAAAUG CUGAUGAGGCCGAAAGGCCGAA AACAGAG
83	1457	UCCACAG CUGAUGAGGCCGAAAGGCCGAA AAUGGAA
93	1458	AUCCUAU CUGAUGAGGCCGAAAGGCCGAA AGUCCAC
93	1458	AUCCUAU CUGAUGAGGCCGAAAGGCCGAA AGUCCAC
93	1458	AUCCUAU CUGAUGAGGCCGAAAGGCCGAA AGUCCAC
96	1459	AUGAUCC CUGAUGAGGCCGAAAGGCCGAA AUUAGUC
96	1459	AUGAUCC CUGAUGAGGCCGAAAGGCCGAA AUUAGUC
101	1460	UAAAGAU CUGAUGAGGCCGAAAGGCCGAA AUCCUAU
104	1461	UGCUAAA CUGAUGAGGCCGAAAGGCCGAA AUGAUCC
104	1461	UGCUAAA CUGAUGAGGCCGAAAGGCCGAA AUGAUCC
106	1462	GAUGCUA CUGAUGAGGCCGAAAGGCCGAA AGAUGAU
107	1463	AGAUGCU CUGAUGAGGCCGAAAGGCCGAA AAGAUGA
107	1463	AGAUGCU CUGAUGAGGCCGAAAGGCCGAA AAGAUGA
108	1464	CAGAUGC CUGAUGAGGCCGAAAGGCCGAA AAAGAUG
108	1464	CAGAUGC CUGAUGAGGCCGAAAGGCCGAA AAAGAUG
131	1465	AAGCCUG CUGAUGAGGCCGAAAGGCCGAA AUGGCAU
142	1466	UGUAGAA CUGAUGAGGCCGAAAGGCCGAA AAGAAGC
142	1466	UGUAGAA CUGAUGAGGCCGAAAGGCCGAA AAGAAGC
143	1467	AUGUAGA CUGAUGAGGCCGAAAGGCCGAA AAAGAAG
143	1467	AUGUAGA CUGAUGAGGCCGAAAGGCCGAA AAAGAAG
143	1467	AUGUAGA CUGAUGAGGCCGAAAGGCCGAA AAAGAAG
143	1467	AUGUAGA CUGAUGAGGCCGAAAGGCCGAA AAAGAAG
144	1468	GAUGUAG CUGAUGAGGCCGAAAGGCCGAA AAAAGAA
144	1468	GAUGUAG CUGAUGAGGCCGAAAGGCCGAA AAAAGAA
144	1468	GAUGUAG CUGAUGAGGCCGAAAGGCCGAA AAAAGAA
147	1469	AGAGAUG CUGAUGAGGCCGAAAGGCCGAA AGAAAAA
153	1470	AGAAACA CUGAUGAGGCCGAAAGGCCGAA AGAUGUA
165	1471	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AUCGAGA
165	1471	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AUCGAGA
165	1471	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AUCGAGA
166	1472	CUCACAA CUGAUGAGGCCGAAAGGCCGAA AAUCGAG
167	1473	GCUCACA CUGAUGAGGCCGAAAGGCCGAA AAAUCGA
167	1473	GCUCACA CUGAUGAGGCCGAAAGGCCGAA AAAUCGA
167	1473	GCUCACA CUGAUGAGGCCGAAAGGCCGAA AAAUCGA
168	1474	GGCUCAC CUGAUGAGGCCGAAAGGCCGAA AAAAUCG
168	1474	GGCUCAC CUGAUGAGGCCGAAAGGCCGAA AAAAUCG
197	1475	UAGAGCC CUGAUGAGGCCGAAAGGCCGAA AUGGAGC
202	1476	GAAUCUA CUGAUGAGGCCGAAAGGCCGAA AGCCAAU
208	1477	AGCCAGG CUGAUGAGGCCGAAAGGCCGAA AUCUAGA
216	1478	AUGGGGA CUGAUGAGGCCGAAAGGCCGAA AGCCAGG
217	1479	GAUGGGG CUGAUGAGGCCGAAAGGCCGAA AAGCCAG
217	1479	GAUGGGG CUGAUGAGGCCGAAAGGCCGAA AAGCCAG
217	1479	GAUGGGG CUGAUGAGGCCGAAAGGCCGAA AAGCCAG
218	1480	UGAUGGG CUGAUGAGGCCGAAAGGCCGAA AAAGCCA
218	1480	UGAUGGG CUGAUGAGGCCGAAAGGCCGAA AAAGCCA
218	1480	UGAUGGG CUGAUGAGGCCGAAAGGCCGAA AAAGCCA
218	1480	UGAUGGG CUGAUGAGGCCGAAAGGCCGAA AAAGCCA
224	1481	AGAACAU CUGAUGAGGCCGAAAGGCCGAA AUGGGGA
224	1481	AGAACAU CUGAUGAGGCCGAAAGGCCGAA AUGGGGA
230	1482	CUUUGGA CUGAUGAGGCCGAAAGGCCGAA AACAUGA
232	1483	UGCUUUG CUGAUGAGGCCGAAAGGCCGAA AGAACAU
232	1483	UGCUUUG CUGAUGAGGCCGAAAGGCCGAA AGAACAU
232	1483	UGCUUUG CUGAUGAGGCCGAAAGGCCGAA AGAACAU
241	1484	AGCUUCA CUGAUGAGGCCGAAAGGCCGAA AUGCUUU
241	1484	AGCUUCA CUGAUGAGGCCGAAAGGCCGAA AUGCUUU
241	1484	AGCUUCA CUGAUGAGGCCGAAAGGCCGAA AUGCUUU
249	1485	CAAGCCA CUGAUGAGGCCGAAAGGCCGAA AGCUUCA
264	1486	AUCAACU CUGAUGAGGCCGAAAGGCCGAA ACAAUUG
287	1487	ACUUGAG CUGAUGAGGCCGAAAGGCCGAA AGUGGUG
295	1488	ACAUGGA CUGAUGAGGCCGAAAGGCCGAA ACUUGAG
295	1488	ACAUGGA CUGAUGAGGCCGAAAGGCCGAA ACUUGAG
296	1489	GACAUGG CUGAUGAGGCCGAAAGGCCGAA AACUUGA
297	1490	GGACAUG CUGAUGAGGCCGAAAGGCCGAA AAACUUG
297	1490	GGACAUG CUGAUGAGGCCGAAAGGCCGAA AAACUUG
314	1491	AGAGAAG CUGAUGAGGCCGAAAGGCCGAA AUGAGCC
314	1491	AGAGAAG CUGAUGAGGCCGAAAGGCCGAA AUGAGCC
315	1492	AAGAGAA CUGAUGAGGCCGAAAGGCCGAA AAUGAGC
315	1492	AAGAGAA CUGAUGAGGCCGAAAGGCCGAA AAUGAGC
317	1493	CAAAGAG CUGAUGAGGCCGAAAGGCCGAA AGAAUGA
318	1494	ACAAAGA CUGAUGAGGCCGAAAGGCCGAA AAGAAUG
318	1494	ACAAAGA CUGAUGAGGCCGAAAGGCCGAA AAGAAUG
320	1495	GCACAAA CUGAUGAGGCCGAAAGGCCGAA AGAAGAA
320	1495	GCACAAA CUGAUGAGGCCGAAAGGCCGAA AGAAGAA
322	1496	CAGCACA CUGAUGAGGCCGAAAGGCCGAA AGAGAAG
322	1496	CAGCACA CUGAUGAGGCCGAAAGGCCGAA AGAGAAG
323	1497	GCAGCAC CUGAUGAGGCCGAAAGGCCGAA AAGAGAA
336	1498	GAAAGAC CUGAUGAGGCCGAAAGGCCGAA AAUCAGC
341	1499	CUUGUGA CUGAUGAGGCCGAAAGGCCGAA AGACGAA
341	1499	CUUGUGA CUGAUGAGGCCGAAAGGCCGAA AGACGAA
342	1500	ACUUGUG CUGAUGAGGCCGAAAGGCCGAA AAGACGA
343	1501	CACUUGU CUGAUGAGGCCGAAAGGCCGAA AAAGACG
343	1501	CACUUGU CUGAUGAGGCCGAAAGGCCGAA AAAGACG
352	1502	AUCUGAA CUGAUGAGGCCGAAAGGCCGAA ACACUUG
355	1503	AACAUCU CUGAUGAGGCCGAAAGGCCGAA AAGACAC
382	1504	UUUCACU CUGAUGAGGCCGAAAGGCCGAA ACUUGGA
408	1505	UAACGGC CUGAUGAGGCCGAAAGGCCGAA AGGCAGC
414	1506	GAGUUGU CUGAUGAGGCCGAAAGGCCGAA ACGGCAA
414	1506	GAGUUGU CUGAUGAGGCCGAAAGGCCGAA ACGGCAA
421	1507	AUGAGGA CUGAUGAGGCCGAAAGGCCGAA AGUUGUA
426	1508	UCUUCAU CUGAUGAGGCCGAAAGGCCGAA AGGAGAG
439	1509	GUCUUCA CUGAUGAGGCCGAAAGGCCGAA ACUCAUC
452	1510	GCCAGUA CUGAUGAGGCCGAAAGGCCGAA AUUCGGU
454	1511	UUGCCAG CUGAUGAGGCCGAAAGGCCGAA AGAUUCG
484	1512	AAUGACA CUGAUGAGGCCGAAAGGCCGAA ACAGCAC
484	1512	AAUGACA CUGAUGAGGCCGAAAGGCCGAA ACAGCAC
488	1513	CAGCAAU CUGAUGAGGCCGAAAGGCCGAA ACAGACA
503	1514	ACACUUU CUGAUGAGGCCGAAAGGCCGAA AGUUUCC
503	1514	ACACUUU CUGAUGAGGCCGAAAGGCCGAA AGUUUCC
520	1515	GUUCUUA CUGAUGAGGCCGAAAGGCCGAA ACUCGGG
535	1516	GUCAUAU CUGAUGAGGCCGAAAGGCCGAA AAGUCCG
536	1517	UGUCAUA CUGAUGAGGCCGAAAGGCCGAA AAAGUCC
538	1518	GUUGUCA CUGAUGAGGCCGAAAGGCCGAA AUAAAGU
553	1519	AAGAGAG CUGAUGAGGCCGAAAGGCCGAA AGGUAGU
553	1519	AAGAGAG CUGAUGAGGCCGAAAGGCCGAA AGGUAGU
556	1520	GAUAAGA CUGAUGAGGCCGAAAGGCCGAA AGUAGGU
556	1520	GAUAAGA CUGAUGAGGCCGAAAGGCCGAA AGUAGGU
560	1521	GGAUGAU CUGAUGAGGCCGAAAGGCCGAA AGAGAGU
561	1522	AGGAUGA CUGAUGAGGCCGAAAGGCCGAA AAGAGAG
561	1522	AGGAUGA CUGAUGAGGCCGAAAGGCCGAA AAGAGAG
561	1522	AGGAUGA CUGAUGAGGCCGAAAGGCCGAA AAGAGAG
566	1523	GGCCCAG CUGAUGAGGCCGAAAGGCCGAA AUGAUAA
566	1523	GGCCCAG CUGAUGAGGCCGAAAGGCCGAA AUGAUAA
581	1524	GGUCUGA CUGAUGAGGCCGAAAGGCCGAA AGGACCA
583	1525	CCGGUCU CUGAUGAGGCCGAAAGGCCGAA AAAGGAC
583	1525	CCGGUCU CUGAUGAGGCCGAAAGGCCGAA AAAGGAC
598	1526	ACAGCUG CUGAUGAGGCCGAAAGGCCGAA AUGUGCC
608	1527	UUUGAAC CUGAUGAGGCCGAAAGGCCGAA ACACAGC
611	1528	UCUUUUG CUGAUGAGGCCGAAAGGCCGAA ACGACAC
611	1528	UCUUUUG CUGAUGAGGCCGAAAGGCCGAA ACGACAC
612	1529	UUCUUUU CUGAUGAGGCCGAAAGGCCGAA AACGACA
641	1530	AGUGUUU CUGAUGAGGCCGAAAGGCCGAA ACUUCAU
649	1531	UAAAGCC CUGAUGAGGCCGAAAGGCCGAA AGUGUUU
649	1531	UAAAGCC CUGAUGAGGCCGAAAGGCCGAA AGUGUUU
655	1532	CUUUACU CUGAUGAGGCCGAAAGGCCGAA AAGCCAA
656	1533	ACUUUAC CUGAUGAGGCCGAAAGGCCGAA AAAGCCA
659	1534	ACAACUU CUGAUGAGGCCGAAAGGCCGAA ACUAAAG
664	1535	GAUGGAC CUGAUGAGGCCGAAAGGCCGAA ACUUUAC
667	1536	UUUGAUG CUGAUGAGGCCGAAAGGCCGAA ACAACUU
671	1537	CAGCUUU CUGAUGAGGCCGAAAGGCCGAA AUGGACA
682	1538	GGUAGAG CUGAUGAGGCCGAAAGGCCGAA AGUCAGC
682	1538	GGUAGAG CUGAUGAGGCCGAAAGGCCGAA AGUCAGC
682	1538	GGUAGAG CUGAUGAGGCCGAAAGGCCGAA AGUCAGC
683	1539	GGGUAGA CUGAUGAGGCCGAAAGGCCGAA AAGUCAG
683	1539	GGGUAGA CUGAUGAGGCCGAAAGGCCGAA AAGUCAG
685	1540	GGGGGUA CUGAUGAGGCCGAAAGGCCGAA AGAAGUC
685	1540	GGGGGUA CUGAUGAGGCCGAAAGGCCGAA AGAAGUC
687	1541	UUGGGGG CUGAUGAGGCCGAAAGGCCGAA AGAGAAG
698	1542	ACUCAGU CUGAUGAGGCCGAAAGGCCGAA AUGUUGG
698	1542	ACUCAGU CUGAUGAGGCCGAAAGGCCGAA AUGUUGG
718	1543	GUCUGCA CUGAUGAGGCCGAAAGGCCGAA AUGGGUU
718	1543	GUCUGCA CUGAUGAGGCCGAAAGGCCGAA AUGGGUU
729	1544	AUCCUUU CUGAUGAGGCCGAAAGGCCGAA AGUGUCU
729	1544	AUCCUUU CUGAUGAGGCCGAAAGGCCGAA AGUGUCU
729	1544	AUCCUUU CUGAUGAGGCCGAAAGGCCGAA AGUGUCU
737	1545	AGCAGGU CUGAUGAGGCCGAAAGGCCGAA AUCCUUU
737	1545	AGCAGGU CUGAUGAGGCCGAAAGGCCGAA AUCCUUU
737	1545	AGCAGGU CUGAUGAGGCCGAAAGGCCGAA AUCCUUU
745	1546	GGAAGCA CUGAUGAGGCCGAAAGGCCGAA AGCAGGU
745	1546	GGAAGCA CUGAUGAGGCCGAAAGGCCGAA AGCAGGU
759	1547	UUUGGGA CUGAUGAGGCCGAAAGGCCGAA ACCCCCG
759	1547	UUUGGGA CUGAUGAGGCCGAAAGGCCGAA ACCCCCG
759	1547	UUUGGGA CUGAUGAGGCCGAAAGGCCGAA ACCCCCG
760	1548	CUUUGGG CUGAUGAGGCCGAAAGGCCGAA AACCCCC
760	1548	CUUUGGG CUGAUGAGGCCGAAAGGCCGAA AACCCCC
760	1548	CUUUGGG CUGAUGAGGCCGAAAGGCCGAA AACCCCC
761	1549	GCUUUGG CUGAUGAGGCCGAAAGGCCGAA AAACCCC
771	1550	GAGAAGC CUGAUGAGGCCGAAAGGCCGAA AGGCUUU
771	1550	GAGAAGC CUGAUGAGGCCGAAAGGCCGAA AGGCUUU
776	1551	ACCAAGA CUGAUGAGGCCGAAAGGCCGAA AAGCGAG
776	1551	ACCAAGA CUGAUGAGGCCGAAAGGCCGAA AAGCGAG
778	1552	CAACCAA CUGAUGAGGCCGAAAGGCCGAA AGAAGCG
784	1553	AUUUUCC CUGAUGAGGCCGAAAGGCCGAA ACCAAGA
803	1554	UGCCAGG CUGAUGAGGCCGAAAGGCCGAA AAUUCUC
803	1554	UGCCAGG CUGAUGAGGCCGAAAGGCCGAA AAUUCUC
803	1554	UGCCAGG CUGAUGAGGCCGAAAGGCCGAA AAUUCUC
812	1555	UCGUAUU CUGAUGAGGCCGAAAGGCCGAA AUGCCAG
812	1555	UCGUAUU CUGAUGAGGCCGAAAGGCCGAA AUGCCAG
816	1556	AUUGUCG CUGAUGAGGCCGAAAGGCCGAA AUUGAUG
816	1556	AUUGUCG CUGAUGAGGCCGAAAGGCCGAA AUUGAUG
824	1557	CCUGGGA CUGAUGAGGCCGAAAGGCCGAA AUUGUCG
825	1558	UCCUGGG CUGAUGAGGCCGAAAGGCCGAA AAUUGUC
826	1559	AUCCUGG CUGAUGAGGCCGAAAGGCCGAA AAAUUGU
834	1560	GAUUCAG CUGAUGAGGCCGAAAGGCCGAA AUCCUGG
841	1561	CAAUUCA CUGAUGAGGCCGAAAGGCCGAA AUUCAGG
841	1561	CAAUUCA CUGAUGAGGCCGAAAGGCCGAA AUUCAGG
850	1562	AAUGGUG CUGAUGAGGCCGAAAGGCCGAA ACAAUUC
869	1563	UGAAAUC CUGAUGAGGCCGAAAGGCCGAA AGUUGGC
869	1563	UGAAAUC CUGAUGAGGCCGAAAGGCCGAA AGUUGGC
869	1563	UGAAAUC CUGAUGAGGCCGAAAGGCCGAA AGUUGGC
873	1564	GUAUUGA CUGAUGAGGCCGAAAGGCCGAA AUCUAGU
873	1564	GUAUUGA CUGAUGAGGCCGAAAGGCCGAA AUCUAGU
874	1565	CGUAUUG CUGAUGAGGCCGAAAGGCCGAA AAUCUAG
875	1566	UCGUAUU CUGAUGAGGCCGAAAGGCCGAA AAAUCUA
885	1567	UGGUUGC CUGAUGAGGCCGAAAGGCCGAA AGUCGUA
899	1568	GACACUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGU
899	1568	GACACUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGU
906	1569	UUAAUGA CUGAUGAGGCCGAAAGGCCGAA ACACUUA
906	1569	UUAAUGA CUGAUGAGGCCGAAAGGCCGAA ACACUUA
908	1570	AUUUAAU CUGAUGAGGCCGAAAGGCCGAA AGACACU
911	1571	CAUAUUU CUGAUGAGGCCGAAAGGCCGAA AUGAGAC
916	1572	AUCUCCA CUGAUGAGGCCGAAAGGCCGAA AUUUAAU
916	1572	AUCUCCA CUGAUGAGGCCGAAAGGCCGAA AUUUAAU
943	1573	CCAGGUG CUGAUGAGGCCGAAAGGCCGAA AGUCCUC
944	1574	CCCAGGU CUGAUGAGGCCGAAAGGCCGAA AAGUCCU
1001	1575	CUGCCCC CUGAUGAGGCCGAAAGGCCGAA AAGAGCA
1034	1576	CGAUGAC CUGAUGAGGCCGAAAGGCCGAA ACGACUG
1037	1577	CAACGAU CUGAUGAGGCCGAAAGGCCGAA ACGACGA
1043	1578	UGAUGAC CUGAUGAGGCCGAAAGGCCGAA ACGAUGA
1046	1579	UGAUGAU CUGAUGAGGCCGAAAGGCCGAA ACAACGA
1049	1580	AUUUGAU CUGAUGAGGCCGAAAGGCCGAA AUGACAA
1060	1581	CUUACAG CUGAUGAGGCCGAAAGGCCGAA AGCAUUU
1060	1581	CUUACAG CUGAUGAGGCCGAAAGGCCGAA AGCAUUU
1060	1581	CUUACAG CUGAUGAGGCCGAAAGGCCGAA AGCAUUU
1060	1581	CUUACAG CUGAUGAGGCCGAAAGGCCGAA AGCAUUU
1061	1582	GCUUACA CUGAUGAGGCCGAAAGGCCGAA AAGCAUU
1080	1583	CUUCUGA CUGAUGAGGCCGAAAGGCCGAA ACAGCUU
1080	1583	CUUCUGA CUGAUGAGGCCGAAAGGCCGAA ACAGCUU
1081	1584	UCUUCUG CUGAUGAGGCCGAAAGGCCGAA AACAGCU
1121	1585	CGAAGGU CUGAUGAGGCCGAAAGGCCGAA AGGCUGU
1121	1585	CGAAGGU CUGAUGAGGCCGAAAGGCCGAA AGGCUGU
1121	1585	CGAAGGU CUGAUGAGGCCGAAAGGCCGAA AGGCUGU
1122	1586	CCGAAGG CUGAUGAGGCCGAAAGGCCGAA AAGGCUG
1126	1587	AGGCCCG CUGAUGAGGCCGAAAGGCCGAA AGGUAAG
1127	1588	CAGGCCC CUGAUGAGGCCGAAAGGCCGAA AAGGUAA
1127	1588	CAGGCCC CUGAUGAGGCCGAAAGGCCGAA AAGGUAA
1144	1589	UUCAGCU CUGAUGAGGCCGAAAGGCCGAA AUGCUUC
1144	1589	UUCAGCU CUGAUGAGGCCGAAAGGCCGAA AUGCUUC
1145	1590	GUUCAGC CUGAUGAGGCCGAAACGCCGAA AAUGCUU
1160	1591	AAAGGAA CUGAUGAGGCCGAAAGGCCGAA ACGGUCU
1162	1592	CUAAAGG CUGAUGAGGCCGAAAGGCCGAA AGACGGU
1163	1593	ACUAAAG CUGAUGAGGCCGAAAGGCCGAA AAGACGG
1167	1594	AAGAACU CUGAUGAGGCCGAAAGGCCGAA AAGGAAG
1177	1595	AUGGACA CUGAUGAGGCCGAAAGGCCGAA AGAAGAA
1181	1596	CCACAUG CUGAUGAGGCCGAAAGGCCGAA ACAGAGA
1181	1596	CCACAUG CUGAUGAGGCCGAAAGGCCGAA ACAGAGA
1192	1597	UACCAUG CUGAUGAGGCCGAAAGGCCGAA AUCCCAC
1199	1598	CACAUAA CUGAUGAGGCCGAAAGGCCGAA ACCAUGU
1201	1599	GCCACAU CUGAUGAGGCCGAAAGGCCGAA AUACCAU
1210	1600	ACCUCAU CUGAUGAGGCCGAAAGGCCGAA AGCCACA
1210	1600	ACCUCAU CUGAUGAGGCCGAAAGGCCGAA AGCCACA
1223	1601	AAAGAAA CUGAUGAGGCCGAAAGGCCGAA AUUGUAC
1225	1602	UGAAAGA CUGAUGAGGCCGAAAGGCCGAA AGAUUGU
1225	1602	UGAAAGA CUGAUGAGGCCGAAAGGCCGAA AGAUUGU
1226	1603	CUGAAAG CUGAUGAGGCCGAAAGGCCGAA AAGAUUG
1227	1604	GCUGAAA CUGAUGAGGCCGAAAGGCCGAA AAAGAUU
1227	1604	GCUGAAA CUGAUGAGGCCGAAAGGCCGAA AAAGAUU
1227	1604	GCUGAAA CUGAUGAGGCCGAAAGGCCGAA AAAGAUU
1229	1605	GUGCUGA CUGAUGAGGCCGAAAGGCCGAA AGAAAGA
1230	1606	GGUGCUG CUGAUGAGGCCGAAAGGCCGAA AAGAAAG
1252	1607	UGUCCGA CUGAUGAGGCCGAAAGGCCGAA AGAUCAG
1274	1608	UUAACUC CUGAUGAGGCCGAAAGGCCGAA AUCUUGU
1310	1609	GGAAAGA CUGAUGAGGCCGAAAGGCCGAA AUCCUCA
1312	1610	AUGGAAA CUGAUGAGGCCGAAAGGCCGAA AAAUCCU
1314	1611	UGAUGGA CUGAUGAGGCCGAAAGGCCGAA AGAAAUC
1316	1612	CCUGAUG CUGAUGAGGCCGAAAGGCCGAA AAAGAAA
1320	1613	GCUUCCU CUGAUGAGGCCGAAAGGCCGAA AUGGAAA
1320	1613	GCUUCCU CUGAUGAGGCCGAAAGGCCGAA AUGGAAA
1339	1614	CCCAGCA CUGAUGAGGCCGAAAGGCCGAA ACUUGCC
1355	1615	AUCAAGC CUGAUGAGGCCGAAAGGCCGAA AUCAAAG
1437	1616	UUUUUCU CUGAUGAGGCCGAAAGGCCGAA AUACCAC
1437	1616	UUUUUCU CUGAUGAGGCCGAAAGGCCGAA AUACCAC
1475	1617	GCAGUAA CUGAUGAGGCCGAAAGGCCGAA ACUAGGC
1477	1618	UUGCAGU CUGAUGAGGCCGAAAGGCCGAA AGACUAG
1487	1619	ACAUAUC CUGAUGAGGCCGAAAGGCCGAA AGUUGCA
1491	1620	CAUGACA CUGAUGAGGCCGAAAGGCCGAA AUCAAGU
1491	1620	CAUGACA CUGAUGAGGCCGAAAGGCCGAA AUCAAGU
1505	1621	AGACACC CUGAUGAGGCCGAAAGGCCGAA ACCAAAC
1530	1622	CUUCAGA CUGAUGAGGCCGAAAGGCCGAA AAGGGCA
1531	1623	UCUUCAG CUGAUGAGGCCGAAAGGCCGAA AAAGGGC
1532	1624	CUCUUCA CUGAUGAGGCCGAAAGGCCGAA AAAAGGG
1532	1624	CUCUUCA CUGAUGAGGCCGAAAGGCCGAA AAAAGGG
1644	1625	ACAUCCC CUGAUGAGGCCGAAAGGCCGAA ACCAUAG
1652	1626	CCGUUUU CUGAUGAGGCCGAAAGGCCGAA ACAUCCC
1652	1626	CCGUUUU CUGAUGAGGCCGAAAGGCCGAA ACAUCCC
1670	1627	UAAUAUU CUGAUGAGGCCGAAAGGCCGAA AUAUUAU
1674	1628	UAUUUAA CUGAUGAGGCCGAAAGGCCGAA AUUUAUA
1676	1629	UUUAUUU CUGAUGAGGCCGAAAGGCCGAA AUAUUUA
1677	1630	UUUUAUU CUGAUGAGGCCGAAAGGCCGAA AAUAUUU
1677	1630	UUUUAUU CUGAUGAGGCCGAAAGGCCGAA AAUAUUU
1694	1631	UUUGCUC CUGAUGAGGCCCAAAGGCCGAA AUACUCU

[0090]

TABLE VI
Human B7-2 Hammerhead Ribozyme Sequences
nt.	SEQ ID	HH Target
Position	NO	Sequence
16	493	GAAAGCU U UGCUUCU
17	494	AAAGCUU U GCUUCUC
21	495	CUUUGCU U CUCUGCU
22	496	UUUGCUU C UCUGCUG
24	497	UGCUUCU C UGCUGCU
34	498	CUGCUGU A ACAGGGA
44	499	AGGGACU A GCACAGA
70	500	GUGGGGU C AUUUCCA
73	501	GGGUCAU U UCCAGAU
74	502	GGUCAUU U CCAGAUA
75	503	GUCAUUU C CAGAUAU
81	504	UCCAGAU A UUAGGUC
83	505	CAGAUAU U AGGUCAC
84	506	AGAUAUU A GGUCACA
88	507	AUUAGGU C ACAGCAG
113	508	AAUGGAU C CCCAGUG
125	509	GUGCACU A UGGGACU
137	510	ACUGAGU A ACAUUCU
142	511	GUAACAU U CUCUUUG
143	512	UAACAUU C UCUUUGU
145	513	ACAUUCU C UUUGUGA
147	514	AUUCUCU U UGUGAUG
148	515	UUCUCUU U GUGAUGG
159	516	AUGGCCU U CCUGCUC
160	517	UGGCCUU C CUGCUCU
166	518	UCCUGCU C UCUGGUG
168	519	CUGCUCU C UGGUGCU
179	520	UGCUGCU C CUCUGAA
182	521	UGCUCCU C UGAAGAU
190	522	UGAAGAU U CAAGCUU
191	523	GAAGAUU C AAGCUUA
197	524	UCAAGCU U AUUUCAA
198	525	CAAGCUU A UUUCAAU
200	526	AGCUUAU U UCAAUGA
201	527	GCUUAUU U CAAUGAG
202	528	CUUAUUU C AAUGAGA
231	529	UGCCAAU U UGCAAAC
232	530	GCCAAUU U GCAAACU
240	531	GCAAACU C UCAAAAC
242	532	AAACUCU C AAAACCA
265	533	GUGAGCU A GUAGUAU
268	534	AGCUAGU A GUAUUUU
489	535	AUGAAUU C UGAACUG
498	536	GAACUGU C AGUGCUU
505	537	CAGUGCU U GCUAACU
509	538	GCUUGCU A ACUUCAG
513	539	GCUAACU U CAGUCAA
514	540	CUAACUU C AGUCAAC
518	541	CUUCAGU C AACCUGA
529	542	CUGAAAU A GUACCAA
532	543	AAAUAGU A CCAAUUU
538	544	UACCAAU U UCUAAUA
539	545	ACCAAUU U CUAAUAU
540	546	CCAAUUU C UAAUAUA
542	547	AAUUUCU A AUAUAAC
545	548	UUCUAAU A UAACAGA
547	549	CUAAUAU A ACAGAAA
561	550	AAUGUGU A CAUAAAU
565	551	UGUACAU A AAUUUGA
569	552	CAUAAAU U UGACCUG
570	553	AUAAAUU U GACCUGC
579	554	ACCUGCU C AUCUAUA
582	555	UGCUCAU C UAUACAC
584	556	CUCAUCU A UACACGG
586	557	CAUCUAU A CACGGUU
593	558	ACACGGU U ACCCAGA
594	559	CACGGUU A CCCAGAA
605	560	AGAACCU A AGAAGAU
619	561	UGAGUGU U UUGCUAA
620	562	GAGUGUU U UGCUAAG
621	563	AGUGUUU U GCUAAGA
625	564	UUUUGCU A AGAACCA
638	565	CAAGAAU U CAACUAU
639	566	AAGAAUU C AACUAUC
644	567	UUCAACU A UCGAGUA
646	568	CAACUAU C GAGUAUG
651	569	AUCGAGU A UGAUGGU
659	570	UGAUGGU A UUAUGCA
661	571	AUGGUAU U AUGCAGA
662	572	UGGUAUU A UGCAGAA
672	573	CAGAAAU C UCAAGAU
674	574	GAAAUCU C AAGAUAA
680	575	UCAAGAU A AUGUCAC
685	576	AUAAUGU C ACAGAAC
696	577	GAACUGU A CGACGUU
703	578	ACGACGU U UCCAUCA
704	579	CGACGUU U CCAUCAG
705	580	GACGUUU C CAUCAGC
709	581	UUUCCAU C AGCUUGU
714	582	AUCAGCU U GUCUGUU
717	583	AGCUUGU C UGUUUCA
904	584	GUCUAAU U CUAUGGA
905	585	UCUAAUU C UAUGGAA
907	586	UAAUUCU A UGGAAAU
935	587	GCGGCCU C GCAACUC
942	588	CGCAACU C UUAUAAA
944	589	CAACUCU U AUAAAUG
945	590	AACUCUU A UAAAUGU
947	591	CUCUUAU A AAUGUGG
1009	592	AAAAAAU C CAUAUAC
1013	593	AAUCCAU A UACCUGA
1015	594	UCCAUAU A CCUGAAA
1026	595	GAAAGAU C UGAUGAA
1045	596	AGCGUGU U UUUAAAA
1046	597	GCGUGUU U UUAAAAG
1047	598	CGUGUUU U UAAAAGU
1048	599	GUGUUUU U AAAAGUU
1049	600	UGUUUUU A AAAGUUC
1055	601	UAAAAGU U CGAAGAC
1056	602	AAAAGUU C GAAGACA
1065	603	AAGACAU C UUCAUGC
1067	604	GACAUCU U CAUGCGA
1068	605	ACAUCUU C AUGCGAC
1085	606	AAGUGAU A CAUGUUU
1091	607	UACAUGU U UUUAAUU
1092	608	ACAUGUU U UUAAUUA
1093	609	CAUGUUU U UAAUUAA
1094	610	AUGUUUU U AAUUAAA
1095	611	UGUUUUU A AUUAAAG
1098	612	UUUUAAU U AAAGAGU
1099	613	UUUAAUU A AAGAGUA
271	614	UAGUAGU A UUUUGGC
273	615	GUAGUAU U UUGGCAG
274	616	UAGUAUU U UGGCAGG
275	617	AGUAUUU U GGCAGGA
294	618	GAAAACU U GGUUCUG
298	619	ACUUGGU U CUGAAUG
299	620	CUUGGUU C UGAAUGA
310	621	AUGAGGU A UACUUAG
312	622	GAGGUAU A CUUAGGC
315	623	GUAUACU U AGGCAAA
316	624	UAUACUU A GGCAAAG
330	625	GAGAAAU U UGACAGU
331	626	AGAAAUU U GACAGUG
340	627	ACAGUGU U CAUUCCA
341	628	CAGUGUU C AUUCCAA
344	629	UGUUCAU U CCAAGUA
345	630	GUUCAUU C CAAGUAU
351	631	UCCAAGU A UAUGGGC
353	632	CAAGUAU A UGGGCCG
368	633	CACAAGU U UUGAUUC
369	634	ACAAGUU U UGAUUCG
370	635	CAAGUUU U GAUUCGG
374	636	UUUUGAU U CGGACAG
375	637	UUUGAUU C GGACAGU
383	638	GGACAGU U GGACCCU
397	639	UGAGACU U CACAAUC
398	640	GAGACUU C ACAAUCU
404	641	UCACAAU C UUCAGAU
406	642	ACAAUCU U CAGAUCA
407	643	CAAUCUU C AGAUCAA
412	644	UUCAGAU C AAGGACA
426	645	AAGGGCU U GUAUCAA
429	646	GGCUUGU A UCAAUGU
431	647	CUUGUAU C AAUGUAU
437	648	UCAAUGU A UCAUCCA
439	649	AAUGUAU C AUCCAUC
442	650	GUAUCAU C CAUCACA
446	651	CAUCCAU C ACAAAAA
469	652	GAAUGAU U CGCAUCC
470	653	AAUGAUU C GCAUCCA
475	654	UUCGCAU C CACCAGA
488	655	GAUGAAU U CUGAACU
721	656	UGUCUGU U UCAUUCC
722	657	GUCUGUU U CAUUCCC
723	658	UCUGUUU C AUUCCCU
726	659	GUUUCAU U CCCUGAU
727	660	UUUCAUU C CCUGAUG
736	661	CUGAUGU U ACGAGCA
737	662	UGAUGUU A CGAGCAA
746	663	GAGCAAU A UGACCAU
754	664	UGACCAU C UUCUGUA
756	665	ACCAUCU U CUGUAUU
757	666	CCAUCUU C UGUAUUC
761	667	CUUCUGU A UUCUGGA
763	668	UCUGUAU U CUGGAAA
764	669	CUGUAUU C UGGAAAC
787	670	CGCGGCU U UUAUCUU
788	671	GCGGCUU U UAUCUUC
789	672	CGGCUUU U AUCUUCA
790	673	GGCUUUU A UCUUCAC
792	674	CUUUUAU C UUCACCU
794	675	UUUAUCU U CACCUUU
795	676	UUAUCUU C ACCUUUC
800	677	UUCACCU U UCUCUAU
801	678	UCACCUU U CUCUAUA
802	679	CACCUUU C UCUAUAG
804	680	CCUUUCU C UAUAGAG
806	681	UUUCUCU A UAGAGCU
808	682	UCUCUAU A GAGCUUG
814	683	UAGAGCU U GAGGACC
824	684	GGACCCU C AGCCUCC
830	685	UCAGCCU C CCCCAGA
844	686	ACCACAU U CCUUGGA
845	687	CCACAUU C CUUGGAU
848	688	CAUUCCU U GGAUUAC
853	689	CUUGGAU U ACAGCUG
854	690	UUGGAUU A CAGCUGU
862	691	CAGCUGU A CUUCCAA
865	692	CUGUACU U CCAACAG
866	693	UGUACUU C CAACAGU
874	694	CAACAGU U AUUAUAU
875	695	AACAGUU A UUAUAUG
877	696	CAGUUAU U AUAUGUG
878	697	AGUUAUU A UAUGUGU
880	698	UUAUUAU A UGUGUGA
892	699	UGAUGGU U UUCUGUC
893	700	GAUGGUU U UCUGUCU
894	701	AUGGUUU U CUGUCUA
895	702	UGGUUUU C UGUCUAA
899	703	UUUCUGU C UAAUUCU
902	704	UCUGUCU A AUUCUAU

[0091]

TABLE VII
Human B7-2 Hammerhead Ribozyme Sequences
nt.	SEQ
Posi-	ID
tion	NO	HH Ribozyme Sequences
16	1632	AGAAGCA CUGAUGAGGCCGAAAGGCCGAA AGCUUUC
17	1633	GAGAAGC CUGAUGAGGCCGAAAGGCCGAA AAGCUUU
21	1634	AGCAGAG CUGAUGAGGCCGAAAGGCCGAA AGCAAAG
22	1635	CAGCAGA CUGAUGAGGCCGAAAGGCCGAA AAGCAAA
24	1636	AGCAGCA CUGAUGAGGCCGAAAGGCCGAA AGAAGCA
34	1637	UCCCUGU CUGAUGAGGCCGAAAGGCCGAA ACAGCAG
44	1638	UCUGUGC CUGAUGAGGCCGAAAGGCCGAA AGUCCCU
70	1639	UGGAAAU CUGAUGAGGCCGAAAGGCCGAA ACCCCAC
73	1640	AUCUGGA CUGAUGAGGCCGAAAGGCCGAA AUGACCC
74	1641	UAUCUGG CUGAUGAGGCCGAAAGGCCGAA AAUGACC
75	1642	AUAUCUG CUGAUGAGGCCGAAAGGCCGAA AAAUGAC
81	1643	GACCUAA CUGAUGAGGCCGAAAGGCCGAA AUCUGGA
83	1644	GUGACCU CUGAUGAGGCCGAAAGGCCGAA AUAUCUG
84	1645	UGUGACC CUGAUGAGGCCGAAAGGCCGAA AAUAUCU
88	1646	CUGCUGU CUGAUGAGGCCGAAAGGCCGAA ACCUAAU
113	1647	CACUGGG CUGAUGAGGCCGAAAGGCCGAA AUCCAUU
125	1648	AGUCCCA CUGAUGAGGCCGAAAGGCCGAA AGUGCAC
137	1649	AGAAUGU CUGAUGAGGCCGAAAGGCCGAA ACUCAGU
142	1650	CAAAGAG CUGAUGAGGCCGAAAGGCCGAA AUGUUAC
143	1651	ACAAAGA CUGAUGAGGCCGAAAGGCCGAA AAUGUUA
145	1652	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AGAAUGU
147	1653	CAUCACA CUGAUGAGGCCGAAAGGCCGAA AGAGAAU
148	1654	CCAUCAC CUGAUGAGGCCGAAAGGCCGAA AAGAGAA
159	1655	GAGCAGG CUGAUGAGGCCGAAAGGCCGAA AGGCCAU
160	1656	AGAGCAG CUGAUGAGGCCGAAAGGCCGAA AAGGCCA
166	1657	CACCAGA CUGAUGAGGCCGAAAGGCCGAA AGCAGGA
168	1658	AGCACCA CUGAUGAGGCCGAAAGGCCGAA AGAGCAG
179	1659	UUCAGAG CUGAUGAGGCCGAAAGGCCGAA AGCAGCA
182	1660	AUCUUCA CUGAUGAGGCCGAAAGGCCGAA AGGAGCA
190	1661	AAGCUUG CUGAUGAGGCCGAAAGGCCGAA AUCUUCA
191	1662	UAAGCUU CUGAUGAGGCCGAAAGGCCGAA AAUCUUC
197	1663	UUGAAAU CUGAUGAGGCCGAAAGGCCGAA AGCUUGA
198	1664	AUUGAAA CUGAUGAGGCCGAAAGGCCGAA AAGCUUG
200	1665	UCAUUGA CUGAUGAGGCCGAAAGGCCGAA AUAAGCU
201	1666	CUCAUUG CUGAUGAGGCCGAAAGGCCGAA AAUAAGC
202	1667	UCUCAUU CUGAUGAGGCCGAAAGGCCGAA AAAUAAG
231	1668	GUUUGCA CUGAUGAGGCCGAAAGGCCGAA AUUGGCA
232	1669	AGUUUGC CUGAUGAGGCCGAAAGGCCGAA AAUUGGC
240	1670	GUUUUGA CUGAUGAGGCCGAAAGGCCGAA AGUUUGC
242	1671	UGGUUUU CUGAUGAGGCCGAAAGGCCGAA AGAGUUU
265	1672	AUACUAC CUGAUGAGGCCGAAAGGCCGAA AGCUCAC
268	1673	AAAAUAC CUGAUGAGGCCGAAAGGCCGAA ACUAGCU
271	1674	GCCAAAA CUGAUGAGGCCGAAAGGCCGAA ACUACUA
273	1675	CUGCCAA CUGAUGAGGCCGAAAGGCCGAA AUACUAC
274	1676	CCUGCCA CUGAUGAGGCCGAAAGGCCGAA AAUACUA
275	1677	UCCUGCC CUGAUGAGGCCGAAAGGCCGAA AAAUACU
294	1678	CAGAACC CUGAUGAGGCCGAAAGGCCGAA AGUUUUC
298	1679	CAUUCAG CUGAUGAGGCCGAAAGGCCGAA ACCAAGU
299	1680	UCAUUCA CUGAUGAGGCCGAAAGGCCGAA AACCAAG
310	1681	CUAAGUA CUGAUGAGGCCGAAAGGCCGAA ACCUCAU
312	1682	GCCUAAG CUGAUGAGGCCGAAAGGCCGAA AUACCUC
315	1683	UUUGCCU CUGAUGAGGCCGAAAGGCCGAA AGUAUAC
316	1684	CUUUGCC CUGAUGAGGCCGAAAGGCCGAA AAGUAUA
330	1685	ACUGUCA CUGAUGAGGCCGAAAGGCCGAA AUUUCUC
331	1686	CACUGUC CUGAUGAGGCCGAAAGGCCGAA AAUUUCU
340	1687	UGGAAUG CUGAUGAGGCCGAAAGGCCGAA ACACUGU
341	1688	UUGGAAU CUGAUGAGGCCGAAAGGCCGAA AACACUG
344	1689	UACUUGG CUGAUGAGGCCGAAAGGCCGAA AUGAACA
345	1690	AUACUUG CUGAUGAGGCCGAAAGGCCGAA AAUGAAC
351	1691	GCCCAUA CUGAUGAGGCCGAAAGGCCGAA ACUUGGA
353	1692	CGGCCCA CUGAUGAGGCCGAAAGGCCGAA AUACUUG
368	1693	GAAUCAA CUGAUGAGGCCGAAAGGCCGAA ACUUGUG
369	1694	CGAAUCA CUGAUGAGGCCGAAAGGCCGAA AACUUGU
370	1695	CCGAAUC CUGAUGAGGCCGAAAGGCCGAA AAACUUG
374	1696	CUGUCCG CUGAUGAGGCCGAAAGGCCGAA AUCAAAA
375	1697	ACUGUCC CUGAUGAGGCCGAAAGGCCGAA AAUCAAA
383	1698	AGGGUCC CUGAUGAGGCCGAAAGGCCGAA ACUGUCC
397	1699	GAUUGUG CUGAUGAGGCCGAAAGGCCGAA AGUCUCA
398	1700	AGAUUGU CUGAUGAGGCCGAAAGGCCGAA AAGUCUC
404	1701	AUCUGAA CUGAUGAGGCCGAAAGGCCGAA AUUGUGA
406	1702	UGAUCUG CUGAUGAGGCCGAAAGGCCGAA AGAUUGU
407	1703	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AAGAUUG
412	1704	UGUCCUU CUGAUGAGGCCGAAAGGCCGAA AUCUGAA
426	1705	UUGAUAC CUGAUGAGGCCGAAAGGCCGAA AGCCCUU
429	1706	ACAUUGA CUGAUGAGGCCGAAAGGCCGAA ACAAGCC
431	1707	AUACAUU CUGAUGAGGCCGAAAGGCCGAA AUACAAG
437	1708	UGGAUGA CUGAUGAGGCCGAAAGGCCGAA ACAUUGA
439	1709	GAUGGAU CUGAUGAGGCCGAAAGGCCGAA AUACAUU
442	1710	UGUGAUG CUGAUGAGGCCGAAAGGCCGAA AUGAUAC
446	1711	UUUUUGU CUGAUGAGGCCGAAAGGCCGAA AUGGAUG
469	1712	GGAUGCG CUGAUGAGGCCGAAAGGCCGAA AUCAUUC
470	1713	UGGAUGC CUGAUGAGGCCGAAAGGCCGAA AAUCAUU
475	1714	UCUGGUG CUGAUGAGGCCGAAAGGCCGAA AUGCGAA
488	1715	AGUUCAG CUGAUGAGGCCGAAAGGCCGAA AUUCAUC
489	1716	CAGUUCA CUGAUGAGGCCGAAAGGCCGAA AAUUCAU
498	1717	AAGCACU CUGAUGAGGCCGAAAGGCCGAA ACAGUUC
505	1718	AGUUAGC CUGAUGAGGCCGAAAGGCCGAA AGCACUG
509	1719	CUGAAGU CUGAUGAGGCCGAAAGGCCGAA AGCAAGC
513	1720	UUGACUG CUGAUGAGGCCGAAAGGCCGAA AGUUAGC
514	1721	GUUGACU CUGAUGAGGCCGAAAGGCCGAA AAGUUAG
518	1722	UCAGGUU CUGAUGAGGCCGAAAGGCCGAA ACUGAAG
529	1723	UUGGUAC CUGAUGAGGCCGAAAGGCCGAA AUUUCAG
532	1724	AAAUUGG CUGAUGAGGCCGAAAGGCCGAA ACUAUUU
538	1725	UAUUAGA CUGAUGAGGCCGAAAGGCCGAA AUUGGUA
539	1726	AUAUUAG CUGAUGAGGCCGAAAGGCCGAA AAUUGGU
540	1727	UAUAUUA CUGAUGAGGCCGAAAGGCCGAA AAAUUGG
542	1728	GUUAUAU CUGAUGAGGCCGAAAGGCCGAA AGAAAUU
545	1729	UCUGUUA CUGAUGAGGCCGAAAGGCCGAA AUUAGAA
547	1730	UUUCUGU CUGAUGAGGCCGAAAGGCCGAA AUAUUAG
S61	1731	AUUUAUG CUGAUGAGGCCGAAAGGCCGAA ACACAUU
565	1732	UCAAAUU CUGAUGAGGCCGAAAGGCCGAA AUGUACA
569	1733	CAGGUCA CUGAUGAGGCCGAAAGGCCGAA AUUUAUG
570	1734	GCAGGUC CUGAUGAGGCCGAAAGGCCGAA AAUUUAU
579	1735	UAUAGAU CUGAUGAGGCCGAAAGGCCGAA AGCAGGU
582	1736	GUGUAUA CUGAUGAGGCCGAAAGGCCGAA AUGAGCA
584	1737	CCGUGUA CUGAUGAGGCCGAAAGGCCGAA AGAUGAG
586	1738	AACCGUG CUGAUGAGGCCGAAAGGCCGAA AUAGAUG
593	1739	UCUGGGU CUGAUGAGGCCGAAAGGCCGAA ACCGUGU
594	1740	UUCUGGG CUGAUGAGGCCGAAAGGCCGAA AACCGUG
605	1741	AUCUUCU CUGAUGAGGCCGAAAGGCCGAA AGGUUCU
619	1742	UUAGCAA CUGAUGAGGCCGAAAGGCCGAA ACACUCA
620	1743	CUUAGCA CUGAUGAGGCCGAAAGGCCGAA AACACUC
621	1744	UCUUAGC CUGAUGAGGCCGAAAGGCCGAA AAACACU
625	1745	UGGUUCU CUGAUGAGGCCGAAAGGCCGAA AGCAAAA
638	1746	AUAGUUG CUGAUGAGGCCGAAAGGCCGAA AUUCUUG
639	1747	GAUAGUU CUGAUGAGGCCGAAAGGCCGAA AAUUCUU
644	1748	UACUCGA CUGAUGAGGCCGAAAGGCCGAA AGUUGAA
646	1749	CAUACUC CUGAUGAGGCCGAAAGGCCGAA AUAGUUG
651	1750	ACCAUCA CUGAUGAGGCCGAAAGGCCGAA ACUCGAU
659	1751	UGCAUAA CUGAUGAGGCCGAAAGGCCGAA ACCAUCA
661	1752	UCUGCAU CUGAUGAGGCCGAAAGGCCGAA AUACCAU
662	1753	UUCUGCA CUGAUGAGGCCGAAAGGCCGAA AAUACCA
672	1754	AUCUUGA CUGAUGAGGCCGAAAGGCCGAA AUUUCUG
674	1755	UUAUCUU CUGAUGAGGCCGAAAGGCCGAA AGAUUUC
680	1756	GUGACAU CUGAUGAGGCCGAAAGGCCGAA AUCUUGA
685	1757	GUUCUGU CUGAUGAGGCCGAAAGGCCGAA ACAUUAU
696	1758	AACGUCG CUGAUGAGGCCGAAAGGCCGAA ACAGUUC
703	1759	UGAUGGA CUGAUGAGGCCGAAAGGCCGAA ACGUCGU
704	1760	CUGAUGG CUGAUGAGGCCGAAAGGCCGAA AACGUCG
705	1761	GCUGAUG CUGAUGAGGCCGAAAGGCCGAA AAACGUC
709	1762	ACAAGCU CUGAUGAGGCCGAAAGGCCGAA AUGGAAA
714	1763	AACAGAC CUGAUGAGGCCGAAAGGCCGAA AGCUGAU
717	1764	UGAAACA CUGAUGAGGCCGAAAGGCCGAA ACAAGCU
721	1765	GGAAUGA CUGAUGAGGCCGAAAGGCCGAA ACAGACA
722	1766	GGGAAUG CUGAUGAGGCCGAAAGGCCGAA AACAGAC
723	1767	AGGGAAU CUGAUGAGGCCGAAAGGCCGAA AAACAGA
726	1768	AUCAGGG CUGAUGAGGCCGAAAGGCCGAA AUGAAAC
727	1769	CAUCAGG CUGAUGAGGCCGAAAGGCCGAA AAUGAAA
736	1770	UGCUCGU CUGAUGAGGCCGAAAGGCCGAA ACAUCAG
737	1771	UUGCUCG CUGAUGAGGCCGAAAGGCCGAA AACAUCA
746	1772	AUGGUCA CUGAUGAGGCCGAAAGGCCGAA AUUGCUC
754	1773	UACAGAA CUGAUGAGGCCGAAAGGCCGAA AUGGUCA
756	1774	AAUACAG CUGAUGAGGCCGAAAGGCCGAA AGAUGGU
757	1775	GAAUACA CUGAUGAGGCCGAAAGGCCGAA AAGAUGG
761	1776	UCCAGAA CUGAUGAGGCCGAAAGGCCGAA ACAGAAG
763	1777	UUUCCAG CUGAUGAGGCCGAAAGGCCGAA AUACAGA
764	1778	GUUUCCA CUGAUGAGGCCGAAAGGCCGAA AAUACAG
787	1779	AAGAUAA CUGAUGAGGCCGAAAGGCCGAA AGCCGCG
788	1780	GAAGAUA CUGAUGAGGCCGAAAGGCCGAA AAGCCGC
789	1781	UGAAGAU CUGAUGAGGCCGAAAGGCCGAA AAAGCCG
790	1782	GUGAAGA CUGAUGAGGCCGAAAGGCCGAA AAAAGCC
792	1783	AGGUGAA CUGAUGAGGCCGAAAGGCCGAA AUAAAAG
794	1784	AAAGGUG CUGAUGAGGCCGAAAGGCCGAA AGAUAAA
795	1785	GAAAGGU CUGAUGAGGCCGAAAGGCCGAA AAGAUAA
800	1786	AUAGAGA CUGAUGAGGCCGAAAGGCCGAA AGGUGAA
801	1787	UAUAGAG CUGAUGAGGCCGAAAGGCCGAA AAGGUGA
802	1788	CUAUAGA CUGAUGAGGCCGAAAGGCCGAA AAAGGUG
804	1789	CUCUAUA CUGAUGAGGCCGAAAGGCCGAA AGAAAGG
806	1790	AGCUCUA CUGAUGAGGCCGAAAGGCCGAA AGAGAAA
808	1791	CAAGCUC CUGAUGAGGCCGAAAGGCCGAA AUAGAGA
814	1792	GGUCCUC CUGAUGAGGCCGAAAGGCCGAA AGCUCUA
824	1793	GGAGGCU CUGAUGAGGCCGAAAGGCCGAA AGGGUCC
830	1794	UCUGGGG CUGAUGAGGCCGAAAGGCCGAA AGGCUGA
844	1795	UCCAAGG CUGAUGAGGCCGAAAGGCCGAA AUGUGGU
845	1796	AUCCAAG CUGAUGAGGCCGAAAGGCCGAA AAUGUGG
848	1797	GUAAUCC CUGAUGAGGCCGAAAGGCCGAA AGGAAUG
853	1798	CAGCUGU CUGAUGAGGCCGAAAGGCCGAA AUCCAAG
854	1799	ACAGCUG CUGAUGAGGCCGAAAGGCCGAA AAUCCAA
862	1800	UUGGAAG CUGAUGAGGCCGAAAGGCCGAA ACAGCUG
865	1801	CUGUUGG CUGAUGAGGCCGAAAGGCCGAA AGUACAG
866	1802	ACUGUUG CUGAUGAGGCCGAAAGGCCGAA AAGUACA
874	1803	AUAUAAU CUGAUGAGGCCGAAAGGCCGAA ACUGUUG
875	1804	CAUAUAA CUGAUGAGGCCGAAAGGCCGAA AACUGUU
877	1805	CACAUAU CUGAUGAGGCCGAAAGGCCGAA AUAACUG
878	1806	ACACAUA CUGAUGAGGCCGAAAGGCCGAA AAUAACU
880	1807	UCACACA CUGAUGAGGCCGAAAGGCCGAA AUAAUAA
892	1808	GACAGAA CUGAUGAGGCCGAAAGGCCGAA ACCAUCA
893	1809	AGACAGA CUGAUGAGGCCGAAAGGCCGAA AACCAUC
894	1810	UAGACAG CUGAUGAGGCCGAAAGGCCGAA AAACCAU
895	1811	UUAGACA CUGAUGAGGCCGAAAGGCCGAA AAAACCA
899	1812	AGAAUUA CUGAUGAGGCCGAAAGGCCGAA ACAGAAA
901	1813	AUAGAAU CUGAUGAGGCCGAAAGGCCGAA AGACAGA
904	1814	UCCAUAG CUGAUGAGGCCGAAAGGCCGAA AUUAGAC
905	1815	UUCCAUA CUGAUGAGGCCGAAAGGCCGAA AAUUAGA
907	1816	AUUUCCA CUGAUGAGGCCGAAAGGCCGAA AGAAUUA
935	1817	GAGUUGC CUGAUGAGGCCGAAAGGCCGAA AGGCCGC
942	1818	UUUAUAA CUGAUGAGGCCGAAAGGCCGAA AGUUGCG
944	1819	CAUUUAU CUGAUGAGGCCGAAAGGCCGAA AGAGUUG
945	1820	ACAUUUA CUGAUGAGGCCGAAAGGCCGAA AAGAGUU
947	1821	CCACAUU CUGAUGAGGCCGAAAGGCCGAA AUAAGAG
1009	1822	GUAUAUG CUGAUGAGGCCGAAAGGCCGAA AUUUUUU
1013	1823	UCAGGUA CUGAUGAGGCCGAAAGGCCGAA AUGGAUU
1015	1824	UUUCAGG CUGAUGAGGCCGAAAGGCCGAA AUAUGGA
1026	1825	UUCAUCA CUGAUGAGGCCGAAAGGCCGAA AUCUUUC
1045	1826	UUUUAAA CUGAUGAGGCCGAAAGGCCGAA ACACGCU
1046	1827	CUUUUAA CUGAUGAGGCCGAAAGGCCGAA AACACGC
1047	1828	ACUUUUA CUGAUGAGGCCGAAAGGCCGAA AAACACG
1048	1829	AACUUUU CUGAUGAGGCCGAAAGGCCGAA AAAACAC
1049	1830	GAACUUU CUGAUGAGGCCGAAAGGCCGAA AAAAACA
1055	1831	GUCUUCG CUGAUGAGGCCGAAAGGCCGAA ACUUUUA
1056	1832	UGUCUUC CUGAUGAGGCCGAAAGGCCGAA AACUUUU
1065	1833	GCAUGAA CUGAUGAGGCCGAAAGGCCGAA AUGUCUU
1067	1834	UCGCAUG CUGAUGAGGCCGAAAGGCCGAA AGAUGUC
1068	1835	GUCGCAU CUGAUGAGGCCGAAAGGCCGAA AAGAUGU
1085	1836	AAACAUG CUGAUGAGGCCGAAAGGCCGAA AUCACUU
1091	1837	AAUUAAA CUGAUGAGGCCGAAAGGCCGAA ACAUGUA
1092	1838	UAAUUAA CUGAUGAGGCCGAAAGGCCGAA AACAUGU
1093	1839	UUAAUUA CUGAUGAGGCCGAAAGGCCGAA AAACAUG
1094	1840	UUUAAUU CUGAUGAGGCCGAAAGGCCGAA AAAACAU
1095	1841	CUUUAAU CUGAUGAGGCCGAAAGGCCGAA AAAAACA
1098	1842	ACUCUUU CUGAUGAGGCCGAAAGGCCGAA AUUAAAA
1099	1843	UACUCUU CUGAUGAGGCCGAAAGGCCGA AAAUUAAA

[0092]

TABLE VIII
Mouse B7-2 Hammerhead Ribozyme Target Sequences
nt.		HH Target	nt.		HH Target
Position	SEQ ID NO	Sequence	Position	SEQ ID NO	Sequence
47	705	ACGGACU u GaACAaC	194	724	CuUAuUU C aAUGGgA
47	705	aCggACU U gaACAAC	208	775	aCUGCaU a UCUGCCG
66	706	CUCCUgU a gACGUgU	210	776	UGCaUaU C UGCCGug
66	706	CUccUgU A gACGUGu	223	777	UGCCCAU U UaCAAAg
74	707	gACGUGU u CCagAAC	223	777	UGCCCAU U UACAaAg
83	708	CaGaACU U aCggaAG	224	778	GCCCAUU U aCAAAgg
134	709	CaAuCCU U aUCUUUG	225	779	CCCAUUU a CAaAggC
134	709	CaauCCU U AUCUUug	225	779	CCCaUUU a CAAAgGC
134	709	CaAUCCU U AuCUUUg	242	780	AAaACAU a agCCUGa
134	709	CAaUCCU U AUCUuUG	260	781	AGCUgGU A GUAUUUU
134	709	CAAuCCU U AUCuuUG	260	781	aGCuGgU a gUAUuUU
135	710	aAuCCUU a UCUUUGU	263	782	UgGUAGU A UUUUGGC
135	710	aAUCCUU a UCUuUgu	263	782	UGgUaGU a UUuUGgC
135	710	AaUCCUU A UCUuUGU	265	615	GUAGUAU U UUGGCAG
135	710	aAUCCUU a UCUuUgU	265	615	guAGUAU u UuGGCaG
137	711	uCCUUaU C UUUGUGA	266	616	UAGUAUU U UGGCAGG
137	711	UCCUUAU C UuUGUGA	266	616	uAGUaUU U UGgCAgG
137	711	UCCuUAU C uuUGugA	266	616	UAgUauU u UGGCAgg
139	712	CUUaUCU U UGUGACa	267	617	AGUAUUU U GGCAGGA
140	713	UUaUCUU U GUGACaG	267	617	AGUaUUU U GgCAgGA
140	713	UUaUCuU U guGACAG	286	783	CAAAAgU U GGUUCUG
149	714	UGACaGU C UUGCUgA	286	783	CAAaagU U GgUUCuG
151	715	ACAGuCU U GGUgaUC	290	784	AgUUGGU U CUGUACG
151	715	ACaGuCU U gCUGaUC	291	785	gUUGGUU C UGuACGA
158	716	UgCuGAU C UCAGaUg	295	786	GUUCugU a CgAGCAC
158	716	UgCUGaU C UCaGaUG	304	787	GAGCaCU A uUUgGGC
158	716	UGCUgAU C uCAgaUg	307	788	cacUAUU u GGgCACA
158	716	UgCugAU C UCagAUg	323	789	AGAAACU U GAUAGUG
160	717	CUGaUCU C aGaUGCU	343	790	gCCAAGU A CCUGGGC
160	717	CUGaUCU C AgAuGCU	343	790	gCCAagU a CCUgGGC
170	718	AUGCuGU u UCCgUgG	361	791	ACgAGCU U UGACagG
171	719	UGCUGuU u CCgUGgA	381	792	CUGgACU a UaCGACtU
172	720	gCUgUuU C agUgGAG	383	793	GgACUCU A CGACuUC
189	721	GCaaGCU u AUUUCaA	383	793	GGACuCU a CGaCUuC
189	721	gCAAGCU U AUUUCAA	389	794	uACGaCU u CaCAaUG
189	721	GCaaGCU u AuUUCAa	389	794	UaCGACU U CACAAUg
190	525	CAAGCUU A UUUCAAU	390	795	aCGACUIU C ACAAUgU
190	525	CaAgCUU a uUUCaAU	390	795	ACgACUEU C aCAAUgU
192	722	AGCUUAU U UCAAUGg	398	796	ACAaUGU U CAgauCA
192	722	aGCUUaU u UCAAUGg	398	796	ACAAUgU U CAGAUCA
193	723	GCUUAUUU CAAUGgG	398	796	ACaAuGU U CagAUCA
193	723	GCuUAuUU CaAUGGg	399	725	CAaUGUU C AgauCAA
194	724	CUUAUUEUC AAUGgGA	399	725	CAAUgUU C AGAUCAA
399	725	CaAuGUUC agAUCAa	658	797	CAGAUAU C ACaagAu
399	725	CaAUGUUC aGAuCAA	658	797	CAgauAu C ACAAgAu
399	725	CAaUguUC aGAUCAa	658	797	CAGAuAU C aCAAGAU
399	725	CAAuGuUC aGAUCAA	658	797	CaGAUaU C ACaAGau
399	725	CAauguUC agAUCAA	666	798	aCAAGAU A AUGUCAC
404	644	UUCAGAUC AAGGACA	666	798	ACAagaU a AUGuCAC
404	644	UuCAGaUC aAGGACa	671	576	AUaAuGU C ACAGaAC
418	726	aUGgGCUC GUAugAU	671	576	aUAAUgU C ACAGAAC
418	726	AuGGGCUC GUAUgAu	671	576	AUAAUGU C ACAGAAC
428	726	AUggGCUC GUaUGaU	682	799	gAACUgU U CAGUAUC
421	727	gGCUCgUa UGAUUgU	683	800	aACUGuU C aGuAUCu
421	727	ggCUCgUA UgAuUGU	683	800	AACUGuU C agUaUCU
429	728	UgAuUGUu UuAUaCA	691	801	aguaUCU C CAaCAGC
429	728	UGAUuGUu UUAUaCA	691	801	agUAUCU C CAaCagC
431	729	AuUgUuUu AUACAAa	691	801	aGUAuCU C CAACAGC
431	729	AUuGUuUU AUaCAaA	701	802	aCaGCCU C UCUCUUu
432	730	UuGUuUUA UaCAaAA	701	802	aCagCCU C UCUCUuU
432	730	UuGUtUUUa UaCaaAA	703	803	AGCCUCU C UCUUUCA
432	730	uUGUUUUa uACaAAA	703	803	aGCCUCU C UCUUuCa
461	731	gAUCaAUu AUCCuCC	707	804	UCUCUCU U UCAUUCC
462	732	AuCaAUUa uCCUCCA	707	804	UCUCUCU u UCAUUCC
464	733	CAauUaUC CUCCaAC	708	805	CUCUCUU U CAUUCCC
467	734	uUAUCCUC CAaCAgA	709	806	UCUCUUU C AUUCCCg
467	734	UUauCCUC CAaCAGA	709	806	UCUCUuU C auuCCCG
467	734	UUaUCCUC CAACAGA	709	806	UCUCUuU C AUUCCC9
467	734	UuAuCCUC CaaCAGA	712	807	CUtUUCaU U CCCgGaU
490	735	GAACUGUC AGUGaUC	712	807	CuuUCAU U CCCgGAU
497	736	CAGUGaUC GCCAACU	712	807	CuUuCAU u CCCGGaU
505	737	GCCAACUU CAGUgAA	712	807	CUtUUCAU U CCCgGAU
506	738	CCAACUUC AGUgAAC	712	807	CU1	UUCAU u CCCggaU
506	738	CCAaCUUC aGUgaaC	713	808	UUUCAUU C CCgGAUg
521	739	CUGAAAUA aaACugg	713	808	UUUCAUU C CCgGAUG
531	740	ACUGgCUC AgAaUgU	732	809	GuGgCAU a UGACCGU
539	741	agaaUGUA ACAGGaA	732	809	GuGgCAU A UGACCgU
550	742	GgAaAuUC uGGCAuA	740	810	UGACCgU U gUgUGUg
550	742	ggAAaUUC UggCAUA	749	811	UgUGUgU U CUGGAAA
557	743	CuggCAUA AAUUUGA	749	811	uGuGUGU U CUggAAA
561	552	CAUAAAUU UGACCUG	750	812	gUGUgUU C UGGAAAC
562	553	AUAAAUUU GACCUGC	750	812	GuGUGUU C UggAAAC
576	744	CaCgUCUA agCAaGG	773	813	ugAAGaU U UCCUCCa
585	745	gCAaGGUC ACCCgaA	778	814	aUUUcCU C CaAACCu
597	746	gaAACCUA AGAAGAU	788	815	AACCUCU C AAuuuCA
607	747	AaGaUgUa UUUUCUg	798	816	UUUCaCU C aAGAGuU
611	748	UGUaUUUu CUgAuAa	805	817	CAagAGU U UCCAUCU
625	749	ACUAAUUC AACUAau	805	817	CAAgAGU U uCCAUCU
630	750	UUCAACUA auGAGUA	806	818	AAgAGUU u CCAUCUC
630	750	UtUCAACUA AuGAGUA	811	819	LTTUUCCAU C uCCUCaa
637	751	AauGAGUA UGgUGaU	811	819	uUUCCaU C UCCUCaA
656	752	uGCAgaUa UCACAAg	813	820	uCCAUCU C CUCaAaC
836	753	aGgAGAUU aCAGCUU
836	753	aggaGAUU ACAGCUu
837	754	GgAGAUUa CAGCUUC
848	755	CUUCAGUu ACugUGg
860	756	UGGCCCUC CUCCUug
860	756	UggCCCuC CUCCuug
878	757	ugCUGCUC AUCauUg
951	758	GCGGgaUa GuAACgC
974	759	AgaCuAUC aACCUGA
989	760	aGgaACuU GaACCCC
1006	761	auUgCUUC aGCAAAa
1055	762	AAAgAGUu aaAAaUU
1056	763	AaGAgUUa aaAAuUG
1062	764	UAAAAAUu gCUuUgC
1092	765	CAgaGUUu CUCAGAA
1095	766	aGUUcCUC AgAaUUC
1101	767	UCAgAAUU CaaAaAU
1101	767	uCAGAAUU CAAaaAU
1101	767	UCAgAaUU CaAAaAu
1111	768	aAaAUGUU CUCAgCU
1112	769	AaAUGUUC UCAgCUg
1128	770	UUgGAaUu CUACAGU
1128	770	UUGGAaUu CuaCaGU
1131	771	GAAuUCUa CAGUUgA
1131	771	GAauUCUa CAgUUGA
1141	772	GuUGAAUa aUuAAag
1144	773	gaaUAAUU AAAGAaC
1145	774	AAuAaUUa aAgaACA

[0093]

TABLE IX
Mouse B7-2 Hammerhead Ribozyme Sequences
nt.	SEQ
Posi-	ID
tion	NO	HH Ribozyme Sequences
47	1844	GUUGUUC CUGAUGAGGCCGAAAGGCCGAA AGUCCGU
47	1844	GUUGUUC CUGAUGAGGCCGAAAGGCCGAA AGUCCGU
66	1545	ACACGUC CUGAUGAGGCCGAAAGGCCGAA ACAGGAG
66	1845	ACACGUC CUGAUGAGGCCGAAAGGCCGAA ACAGGAG
74	1846	GUUCUGG CUGAUGAGGCCGAAAGGCCGAA ACACGUC
83	1847	CUUCCGU CUGAUGAGGCCGAAAGGCCGAA AGUUCUG
134	1848	CAAAGAU CUGAUGAGGCCGAAAGGCCGAA AGGAUUG
134	1848	CAAAGAU CUGAUGAGGCCGAAAGGCCGAA AGGAUUG
134	1848	CAAAGAU CUGAUGAGGCCGAAAGGCCGAA AGGAUUG
134	1848	CAAAGAU CUGAUGAGGCCGAAAGGCCGAA AGGAUUG
134	1848	CAAAGAU CUGAUGAGGCCGAAAGGCCGAA AGGAUUG
135	1849	ACAAAGA CUGAUGAGGCCGAAAGGCCGAA AAGGAUU
135	1849	ACAAAGA CUGAUGAGGCCGAAAGGCCGAA AAGGAUU
135	1849	ACAAAGA CUGAUGAGGCCGAAAGGCCGAA AAGGAUU
135	1849	ACAAAGA CUGAUGAGGCCGAAAGGCCGAA AAGGAUU
137	1850	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AUAAGGA
137	1850	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AUAAGGA
137	1850	UCACAAA CUGAUGAGGCCGAAAGGCCGAA AUAAGGA
139	1851	UGUCACA CUGAUGAGGCCGAAAGGCCGAA AGAUAAG
140	1852	CUGUCAC CUGAUGAGGCCGAAAGGCCGAA AAGAUAA
140	1852	CUGUCAC CUGAUGAGGCCGAAAGGCCGAA AAGAUAA
149	1853	UCAGCAA CUGAUGAGGCCGAAAGGCCGAA ACUGUCA
151	1854	GAUCAGC CUGAUGAGGCCGAAAGGCCGAA AGACUGU
151	1854	GAUCAGC CUGAUGAGGCCGAAAGGCCGAA AGACUGU
158	1855	CAUCUGA CUGAUGAGGCCGAAAGGCCGAA AUCAGCA
158	1855	CAUCUGA CUGAUGAGGCCGAAAGGCCGAA AUCAGCA
158	1855	CAUCUGA CUGAUGAGGCCGAAAGGCCGAA AUCAGCA
158	1855	CAUCUGA CUGAUGAGGCCGAAAGGCCGAA AUCAGCA
160	1856	AGCAUCU CUGAUGAGGCCGAAAGGCCGAA AGAUCAG
160	1856	AGCAUCU CUGAUGAGGCCGAAAGGCCGAA AGAUCAG
170	1857	CCACGGA CUGAUGAGGCCGAAAGGCCGAA ACAGCAU
171	1858	UCCACGG CUGAUGAGGCCGAAAGGCCGAA AACAGCA
172	1859	CUCCACG CUGAUGAGGCCGAAAGGCCGAA AAACAGC
189	1860	UUGAAAU CUGAUGAGGCCGAAAGGCCGAA AGCUUGC
189	1860	UUGAAAU CUGAUGAGGCCGAAAGGCCGAA AGCUUGC
189	1860	UUGAAAU CUGAUGAGGCCGAAAGGCCGAA AGCUUGC
190	1664	AUUGAAA CUGAUGAGGCCGAAAGGCCGAA AAGCUUG
190	1664	AUUGAAA CUGAUGAGGCCGAAAGGCCGAA AAGCUUG
192	1861	CCAUUGA CUGAUGAGGCCGAAAGGCCGAA AUAAGCU
192	1861	CCAUUGA CUGAUGAGGCCGAAAGGCCGAA AUAAGCU
193	1862	CCCAUUG CUGAUGAGGCCGAAAGGCCGAA AAUAAGC
193	1862	CCCAUUG CUGAUGAGGCCGAAAGGCCGAAAAUAAGC
194	1863	UCCCAUU CUGAUGAGGCCGAAAGGCCGAA AAAUAAG
194	1863	UCCCAUU CUGAUGAGGCCGAAAGGCCGAA AAAUAAG
208	1864	CGGCAGA CUGAUGAGGCCGAAAGGCCGAA AUGCAGU
210	1865	CACGGCA CUGAUGAGGCCGAAAGGCCGAA AUAUGCA
223	1866	CUUUGUA CUGAUGAGGCCGAAAGGCCGAA AUGGGCA
223	1866	CUUUGUA CUGAUGAGGCCGAAAGGCCGAA AUGGGCA
224	1867	CCUUUGU CUGAUGAGGCCGAAAGGCCGAA AAUGGGC
225	1868	GCCUUUG CTGAUGAGGCCGAAAGGCCGAA AAAUGGG
225	1868	GCCUUUG CUGAUGAGGCCGAAAGGCCGAA AAAUGGG
242	1869	UCAGGCU CUGAUGAGGCCGAAAGGCCGAA AUGUUUU
260	1870	AAAAUAC CUGAUGAGGCCGAAAGGCCGAA ACCAGCU
260	1870	AAAAUAC CUGAUGAGGCCGAAAGGCCGAA ACCAGCU
263	1871	GCCAAAA CUGAUGAGGCCGAAAGGCCGAA ACUACCA
263	1871	GCCAAAA CUGAUGAGGCCGAAAGGCCGAA ACUACCA
265	1675	CUGCCAA CUGAUGAGGCCGAAAGGCCGAA AUACUAC
265	1675	CUGCCAA CUGAUGAGGCCGAAAGGCCGAA AUACUAC
266	1676	CCUGCCA CUGAUGAGGCCGAAAGGCCGAA AAUACUA
266	1676	CCUGCCA CUGAUGAGGCCGAAAGGCCGAA AAUACUA
266	1676	CCUGCCA CUGAUGAGGCCGAAAGGCCGAA AAUACUA
267	1677	UCCUGCC CUGAUGAGGCCGAAAGGCCGAA AAAUAAU
267	1677	UCCUGCC CUGAUGAGGCCGAAAGGCCGAA AAAUACU
286	1872	CAGAACC CUGAUGAGGCCGAAAGGCCGAA ACUUUUG
286	1872	CAGAACC CUGAUGAGGCCGAAAGGCCGAA ACUUUUG
290	1873	CGUACAG CUGAUGAGGCCGAAAGGCCGAA ACCAACU
291	1874	UCGUACA CUGAUGAGGCCGAAAGGCCGAA AACCAAC
295	1875	GUGCUCG CUGAUGAGGCCGAAAGGCCGAA ACAGAAC
304	1876	GCCCAAA CUGAUGAGGCCGAAAGGCCGAA AGUGCUC
307	1877	UGUGCCC CUGAUGAGGCCGAAAGGCCGAA AAUAGUG
323	1878	CACUAUC CUGAUGAGGCCGAAAGGCCGAA AGUUUCU
343	1879	GCCCACG CUGAUGAGGCCGAAAGGCCGAA ACUUGGC
343	1879	GCCCAGG CUGAUGAGGCCGAAAGGCCGAA ACUUGGC
361	1880	CCUGUCA CUGAUGAGGCCGAAAGGCCGAA AGCUCGU
381	1881	AGUCGUA CUGAUGAGGCCGAAAGGCCGAA AGUCCAG
383	1882	GAAGUCG CUGAUGAGGCCGAAAGGCCGAA AGAGUCC
383	1882	GAAGUCG CUGAUGAGGCCGAAAGGCCGAA AGAGUCC
389	1883	CAUUGUG CUGAUGAGGCCGAAAGGCCGAA AGUCGUA
389	1883	CAUUGUG CUGAUGAGGCCGAAAGGCCGAA AGUCGUA
390	1884	ACAUUGU CUGAUGAGGCCGAAAGGCCGAA AAGUCGU
390	1884	ACAUUGU CUGAUGAGGCCGAAAGGCCGAA AAGUCGU
398	1885	UGAUCUG CUGAUGAGGCCGAAAGGCCGAA ACAUUGU
398	1885	UGAUCUG CUGAUGAGGCCGAAAGGCCGAA ACAUUGU
398	1885	UGAUCUG CUGAUGAGGCCGAAAGGCCGAA ACAUUGU
399	1886	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AACAUUG
399	1886	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AACAUUG
399	1886	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AACAUUG
399	1886	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AACAUUG
399	1886	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AACAUUG
399	1886	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AACAUUG
399	1886	UUGAUCU CUGAUGAGGCCGAAAGGCCGAA AACAUUG
404	1704	UGUCCUU CUGAUGAGGCCGAAAGGCCGAA AUCUGAA
404	1704	UGUCCUU CUGAUGAGGCCGAAAGGCCGAA AUCUGAA
418	1887	AUCAUAC CUGAUGAGGCCGAAAGGCCGAA AGCCCAU
418	1887	AUCAUAC CUGAUGAGGCCGAAAGGCCGUA AGCCCAU
418	1887	AUCAUAC CUCAUGAGGCCGAAAGGCCGAA AGCCCAU
421	1888	ACAAUCA CUGAUGAGGCCGAAAGGCCGAA ACGAGCC
421	1888	ACAAUCA CUGAUGAGGCCGAAAGGCCGAA ACGAGCC
429	1889	UGUAUAA CUGAUGAGGCCGAAAGGCCGAA ACAAUCA
429	1889	UGUAUAA CUGAUGAGGCCGAAAGGCCGAA ACAAUCA
431	1890	UUUGUAU CUGAUGAGGCCGAAAGGCCGAA AAACAAU
431	1890	UUUGUAU CUGAUGAGGCCGAAAGGCCGAA AAACAAU
432	1891	UUUUGUA CUGAUGAGGCCGAAAGGCCGAA AAAACAA
432	1891	UUUUGUA CUGAUGAGGCCGAAAGGCCGAA AAAACAA
432	1891	UUUUGUA CUGAUGAGGCCGAAAGGCCGAA AAAACAA
461	1892	GGAGGAU CUGAUGAGGCCGAAAGGCCGAA AUUGAUC
462	1893	UGGAGGA CUGAUGAGGCCGAAAGGCCGAA AAUUGAU
464	1894	GUUGGAG CUGAUGAGGCCGAAAGGCCGAA AUAAUUG
467	1895	UCUGUUG CUGAUGAGGCCGAAAGGCCGAA AGGAUAA
467	1895	UCUGUUG CUGAUGAGGCCGAAAGGCCGAA AGGAUAA
467	1895	UCUGUUG CUGAUGAGGCCGAAAGGCCGAA AGGAUAA
467	1895	UCUGUUG CUGAUGAGGCCGAAAGGCCGAA AGGAUAA
490	1896	GAUCACU CUGAUGAGGCCGAAAGGCCGAA ACAGUUC
497	1897	AGUUGGC CUGAUGAGGCCGAAAGGCCGAA AUCACUG
505	1898	UUCACUG CUGAUGAGGCCGAAAGGCCGAA AGUUGGC
506	1899	GUUCACU CUGAUGAGGCCGAAAGGCCGAA AAGUUGG
506	1899	GUUCACU CUGAUGAGGCCGAAAGGCCGAA AAGUUGG
521	1900	CCAGUUU CUGAUGAGGCCGAAAGGCCGAA AUUUCAG
531	1901	ACAUUCU CUGAUGAGGCCGAAAGGCCGAA AGCCAGU
539	1902	UUCCUGU CUGAUGAGGCCGAAAGGCCGAA ACAUUCU
550	1903	UAUGCCA CUGAUGAGGCCGAAAGGCCGAA AAUUUCC
550	1903	UAUGCCA CUGAUGAGGCCGAAAGGCCGAA AAUUUCC
557	1904	UCAAAUU CUGAUGAGGCCGAAAGGCCGAA AUGCCAG
561	1733	CAGGUCA CUGAUGAGGCCGAAAGGCCGAA AUUUAUG
562	1734	GCAGGUC CUGAUGAGGCCGAAAGGCCGAA AAUUUAU
576	1905	CCUUGCU CUGAUGAGGCCGAAAGGCCGAA AGACGUG
585	1906	UUCGGGU CUGAUGAGGCCGAAAGGCCGAA ACCUUGC
597	1907	AUCUUCU CUGAUGAGGCCGAAAGGCCGAA AGGUUUC
607	1908	CAGAAAA CUGAUGAGGCCGAAAGGCCGAA ACAUCUU
611	1909	UUAUCAG CUGAUGAGGCCGAAAGGCCGAA AAAUACA
625	1910	AUUAGUU CUGAUGAGGCCGAAAGGCCGAA AAUUAGU
630	1911	UACUCAU CUGAUGAGGCCGAAAGGCCGAA AGUUGAA
630	1911	UACUCAU CUGAUGAGGCCGAAAGGCCGAA AGUUGAA
637	1912	AUCACCA CUGAUGAGGCCGAAAGGCCGAA ACUCAUU
656	1913	CUUGUGA CUGAUGAGGCCGAAAGGCCGAA AUCUGCA
658	1914	AUCUUGU CUGAUGAGGCCGAAAGGCCGAA AUAUCUG
658	1914	AUCUUGU CUGAUGAGGCCGAAAGGCCGAA AUAUCUG
658	1914	AUCUUGU CUGAUGAGGCCGAAAGGCCGAA AUAUCUG
658	1914	AUCUUGU CUGAUGAGGCCGAAAGGCCGAA AUAUCUG
666	1915	GUGACAU CUGAUGAGGCCGAAAGGCCGAA AUCUUGU
666	1915	GUGACAU CUGAUGAGGCCGAAAGGCCGAA AUCUUGU
671	1757	GUUCUGU CUGAUGAGGCCGAAAGGCCGAA ACAUUAU
671	1757	GUUCUGU CUGAUGAGGCCGAAAGGCCGAA ACAUUAU
671	1757	GUUCUGU CUGAUGAGGCCGAAAGGCCGAA ACAUUAU
682	1916	GAUACUG CUGAUGAGGCCGAAAGGCCGAA ACAGUUC
683	1917	AGAUACU CUGAUGAGGCCGAAAGGCCGAA AACAGUU
683	1917	AGAUACU CUGAUGAGGCCGAAAGGCCGAA AACAGUU
691	1918	GCUGUUG CUGAUGAGGCCGAAAGGCCGAA AGAUACU
691	1918	GCUGUUG CUGAUGAGGCCGAAAGGCCGAA AGAUACU
691	1918	GCUGUUG CUGAUGAGGCCGAAAGGCCGAA AGAUACU
701	1919	AAAGAGA CUGAUGAGGCCGAAAGGCCGAA AGGCUGU
701	1919	AAAGAGA CUGAUGAGGCCGAAAGGCCGAA AGGCUGU
703	1920	UGAAAGA CUGAUGAGGCCGAAAGGCCGAA AGAGGCU
703	1920	UGAAAGA CUGAUGAGGCCGAAAGGCCGAA AAAGGCU
707	1921	GGAAUGA CUGAUGAGGCCGAAAGGCCGAA AGAGAGA
707	1921	GGAAUGA CUGAUGAGGCCGAAAGGCCGAA AGAGAGA
708	1922	GGGAAUG CUGAUGAGGCCGAAAGGCCGAA AAGAGAG
709	1923	CGGGAAU CUGAUGAGGCCGAAAGGCCGAA AAAGAGA
709	1923	CGGGAAU CUGAUGAGGCCGAAAGGCCGAA AAAGAGA
709	1923	CGGGAAU CUGAUGAGGCCGAAAGGCCGAA AAAGAGA
712	1924	AUCCGGG CUGAUGAGGCCGAAAGGCCGAA AUGAAAG
712	1924	AUCCGGG CUGAUGAGGCCGAAAGGCCGAA AUGAAAG
712	1924	AUCCGGG CUGAUGAGGCCGAAAGGCCGAA AUGAAAG
712	1924	AUCCGGG CUGAUGAGGCCGAAAGGCCGAA AUGAAAG
712	1924	AUCCGGG CUGAUGAGGCCGAAAGGCCGAA AUGAAAG
713	1925	CAUCCGG CUGAUGAGGCCGAAAGGCCGAA AAUGAAA
713	1925	CAUCCGG UGAUGAGGCCGAAAGGCCGAAA AAUGAAA
732	1926	ACGGUCA CUGAUGAGGCCGAAAGGCCGAA AUGCCAC
732	1926	ACGGUCA CUGAUGAGGCCGAAAGGCCGAA AUGCCAC
740	1927	CACACAC CUGAUGAGGCCGAAAGGCCGAA ACGGUCA
749	1928	UUUCCAG CUGAUGAGGCCGAAAGGCCGAA ACACACA
749	1928	UUUCCAG CUGAUGAGGCCGAAAGGCCGAA ACACACA
750	1929	GUUUCCA CUGAUGAGGCCGAAAGGCCGAA AACACAC
750	1929	GUUUCCA CUGAUGAGGCCGAAAGGCCGAA AACACAC
773	1930	UGGAGGA CUGAUGAGGCCGAAAGGCCGAA AUCUUCA
778	1931	AGGUUUG CUGAUGAGGCCGAAAGGCCGAA AGGAAAU
788	1932	UGAAAUU UGAUGAGGCCGAAAGGCCGAAA AGAGGUU
798	1933	AACUCUU CUGAUGAGGCCGAAAGGCCGAA AGUGAAA
805	1934	AGAUGGA CUGAUGAGGCCGAAAGGCCGAA ACUCUUG
805	1934	AGAUGGA CUGAUGAGGCCGAAAGGCCGAA ACUCUUG
806	1935	GAGAUGG CUGAUGAGGCCGAAAGGCCGAA AACUCUU
811	1936	UUGAGGA CUGAUGAGGCCGAAAGGCCGAA AUGGAAA
811	1936	UUGAGGA CUGAUGAGGCCGAAAGGCCGAA AUGGAAA
813	1937	GUUUGAG CUGAUGAGGCCGAAAGGCCGAA AGAUGGA
836	1938	AAGCUGU CUGAUGAGGCCGAAAGGCCGAA AUCUCCU
836	1938	AAGCUGU CUGAUGAGGCCGAAAGGCCGAA AUCUCCU
837	1939	GAAGCUG CUGAUGAGGCCGAAAGGCCGAA AAUCUCC
848	1940	CCACAGU CUGAUGAGGCCGAAAGGCCGAA ACUGAAG
860	1941	CAAGGAG CUGAUGAGGCCGAAAGGCCGAA AGGGCCA
860	1941	CAAGGAG CUGAUGAGGCCGAAAGGCCGAA AGGGCCA
878	1942	CAAUGAU CUGAUGAGGCCGAAAGGCCGAA AGCAGCA
951	1943	GCGUUAC CUGAUGAGGCCGAAAGGCCGAA AUCCCGC
974	1944	UCAGGUU CUGAUGAGGCCGAUAGGCCGAA AUAGUCU
989	1945	GGGGUUC CUGAUGAGGCCGAAAGGCCGAA AGUUCCU
1006	1946	UUUUGCU CUGAUGAGGCCGAAAGGCCGAA AAGCAAU
1055	1947	AAUUUUU CUGAUGAGGCCGAAAGGCCCAA ACUCUUU
1056	1948	CAAUUUU CIUGAUGAGGCCGAAAGGCCGA AACUCUU
1062	1949	GCAAAGC CUGAUGAGGCCGAAAGGCCGAA AUUUUUA
1092	1950	UUCUGAG CUGAUGAGGCCGAAAGGCCGAA AACUCUG
1095	1951	GAAUUCU CUGAUGAGGCCGAAAGGCCGAA AGAAACU
1101	1952	AUUUUUG CUGAUGAGGCCGAAAGGCCGAA AUUCUGA
1101	1952	AUUUUUG UGAUGAGGCCGAAAGGCCGAAA AUUCUGA
1101	1952	AUUUUUG CUGAUGAGGCCGAAAGGCCGAA AUUCUGA
1111	1953	AGCUGAG CUGAUGAGGCCGAAAGGCCGAA ACAUUUU
1112	1954	CAGGUGA CUGAUGAGGCCGAAAGGCCGAA AACAUUU
1128	1955	ACUGUAG CUGAUGAGGCCGAAAGGCCGAA AUUCCAA
1128	1955	ACUGUAG CUGAUGAGGCCGAAAGGCCGAA AUUCCAA
1131	1956	UCAACUG CUGAUGAGGCCGAAAGGCCGAA AGAAUUC
1131	1956	UCAACUG CUGAUGAGGCCGAAAGGCCGAA AGAAUUC
1141	1957	CUUUAAU CUGAUGAGGCCGAAAGGCCGAA AUUCAAC
1144	1958	GUUCUUU CUGAUGAGGCCGAAAGGCCGAU AUUAUUC
1145	1959	UGUUCUU CUGAUGAGGCCGAAAGGCCGAA AAUUAUU

[0094]

TABLE X
Human CD40 Hammerhead Ribozyme Target Sequences
nt.	SEQ ID	HH Target
Position	NO	Sequence
9	821	CCUCGCU C GGGCGCC
24	822	CAGUGGU C CUGCCGC
37	823	GCCUGGU C UCACCUC
39	824	CUGGUCU C ACCUCGC
44	825	CUCACCU C GCCAUGG
53	826	CCAUGGU U CGUCUGC
54	827	CAUGGUU C GUCUGCC
57	828	GGUUCGU C UGCCUCU
63	829	UCUGCCU C UGCAGUG
74	830	AGUGCGU C CUCUGGG
77	831	GCGUCCU C UGGGGCU
88	832	GGCUGCU U GCUGACC
101	833	CCGCUGU C CAUCCAG
205	834	UGUCCAU C CAGAACC
239	835	AAACAGU A CCUAAUA
243	836	AGUACCU A AUAAACA
146	837	ACCUAAU A AACAGUC
153	838	AAACAGU C AGUGGUG
262	839	GUGCUGU U CUUUGUG
263	840	UGCUGUU C UUUGUGC
165	841	CUGUEUCU U UGUGCCA
166	842	UGUUCUU U GUGCCAG
208	843	ACAGAGU U CACUGAA
209	844	CAGAGUU C ACUGAAA
227	845	AAUGCCU U CCUUGCG
228	846	AUGCCUU C CUUGCGG
231	847	CCUUCCU U GCGGUGA
247	848	AGCGAAU U CCUAGAC
248	849	GCGAAUU C CUAGACA
252.	850	AAUUCCU A GACACCU
292	851	CACAAAU A CUGCGAC
308	852	CCAACCU A GGGCUUC
314	853	UAGGGCU U CGGGUCC
315	854	AGGGCUU C GGGUCCA
320	855	UUCGGGU C CAGCAGA
337	856	GGCACCU C AGAAACA
353	857	ACACCAU C UGCACCU
381	858	GCACUGU A CGAGUGA
407	859	GCUGUGU C CUGCACC
418	860	CACCGCU C AUGCUCG
424	861	UCAUGCU C GCCCGGC
433	862	CCCGGCU U UGGGGUC
434	863	CCGGCUU U GGGGUCA
755	864	AGGAGAU C AAUUUUC
759	865	GAUCAAU U UUCCCGA
760	866	AUCAAUU U UCCCGAC
761	867	UCAAUUU U CCCGACG
762	868	CAAUUUU C CCGACGA
771	869	CGACGAU C UUCCUGG
773	870	ACGAUCU U CCUGGCU
774	871	CGAUCUU C CUGGCUC
781	872	CCUGGCU C CAACACU
795	873	UGCUGCU C CAGUGCA
810	874	GGAGACU U UACAUGG
811	875	GAGACUU U ACAUGGA
812	876	AGACUUU A CAUGGAU
830	877	AACCGGU C ACCCAGG
855	878	AGAGAGG C GCAUCUC
860	879	GUCGCAU C UCAGUGC
862	880	CGCAUCU C AGUGCAG
927	881	AGGCAGU U GGCCAGA
981	882	GGGAGCU A UGCCCAG
990	883	GCCCAGU C AGUGCCA
440	884	UUGGGGU C AAGCAGA
449	885	AGCAGAU U GCUACAG
453	886	GAUUGCU A CAGGGGU
461	887	CAGGGGU U UCUGAUA
462	888	AGGGGUU U CUGAUAC
463	889	GGGGUUU C UGAUACC
468	890	UUCUGAU A CCAUCUG
473	891	AUACCAU C UGCGAGC
492	892	GCCCAGU C GGCUUCU
496	893	GUCGGCU U CUUCUCC
497	894	UCGGCUU C UUCUCCA
499	895	GGCUUCU U CUCCAAU
500	896	GCUUCUU C UCCAAUG
502	897	UUCUUCU C CAAUGUG
511	898	AAUGUGU C AUCUGCU
514	899	GUGUCAU C UGCUUUC
519	900	AUCUGCU U UCGAAAA
520	901	UCUGCUU U CGAAAAA
521	902	CUGCUUU C GAAAAAU
531	903	AAAAUGU C ACCCUUG
537	904	UCACCCU U GGACAAG
566	905	ACCUGGU U GUGCAAC
599	906	CUGAUGU U GUCUGUG
602	907	AUGUUGU C UGUGGUC
609	908	CUGUGGU C CCCAGGA
618	909	CCAGGAU C GGCUGAG
641	910	UGGUGAU C CCCAUCA
647	911	UCCCCAU C AUCUUCG
650	912	CCAUCAU C UUCGGGA
652	913	AUCAUCU U CGGGAUC
653	914	UCAUCUU C GGGAUCC
659	915	UCGGGAU C CUGUUUG
664	916	AUCCUGU U UGCCAUC
665	917	UCCUGUU U GCCAUCC
671	918	UUGCCAU C CUCUUGG
674	919	CCAUCCU C UUGGUGC
676	920	AUCCUCU U GGUGCUG
686	921	UGCUGGU C UUUAUCA
688	922	CUGGUCU U UAUCAAA
689	923 UGGUCUU U AUCAAAA
690	924	GGUCUUU A UCAAAAA
692	925	UCUUUAU C AAAAAGG
720	926	AACCAAU A AGGCCCC

[0095]

TABLE XI
Human CD40 Hammerhead Ribozyme Sequences
nt.	SEQ
Posi-	ID
tion	NO	HH Ribozyme Sequences
9	1960	GGCGCCC CUGAUGAGGCCGAAAGGCCGAA AGCGAGG
24	1961	GCGGCAG CUGAUGAGGCCGAAAGGCCGAA ACCACUG
37	1962	GAGGUGA CUGAUGAGGCCGAAAGGCCGAA ACCAGGC
39	1963	GCGAGGU CUGAUGAGGCCGAUAGGCCGAA AGACCAG
44	1964	CCAUGGC CUGAUGAGGCCGAAAUACCGAA AGGUGAG
53	1965	GCAGACG CUGAUGAGGCCGAAAGGCCGUA ACCAUGG
54	1966	GGCAGAC CUGAUGAGGCCGAAAGGCCGAA AACCAUG
57	1967	AGAGGCA CUGAUGAGGCCGAAAGGCCGUA ACGAACC
63	1968	CACUGCA CUGAUGAGGCCGAAAGGCCGAA AGGCAGA
74	1969	CCCAGAG CUGAUGAGGCCGAAAGGCCGAA ACGCACU
77	1970	AGCCCCA CUGAUGAGGCCGAAAGGCCGAA AGGACGC
88	1971	GGUCAGC CUGAUGAGGCCGAAAGGCCGAA AGCAGCC
101	1972	CUGGAUG CUGAUGAGGCCGAAAGGCCGAA ACAGCGG
105	1973	GGUUCUG CUGAUGAGGCCGAAAGGCCGAA AUGGACA
139	1974	UAUUAGG CUGAUGAGGCCGAAAGGCCGAA ACUGUUU
143	1975	UGUUUAU CUGAUGAGGCCGAAAGGCCGAA AGGUACU
146	1976	GACUGUU CUGAUGAGGCCGAAAGGCCGAA AUUAGGU
153	1977	CAGCACU CUGAUGAGGCCGAAAGGCCGAA ACUGUUU
162	1978	CACAAAG CUGAUGAGGCCGAAAGGCCGAA ACAGCAC
163	1979	GCACAAA CUGAUGAGGCCGAAAGGCCGAA AACAGCA
165	1980	UGGCACA CUGAUGAGGCCGAUUCGCCGAA AGAACAG
166	1981	CUGGCAC CUGAUGAGGCCGAAAGGCCGAA AAGAACA
208	1982	UUCAGUG CUGAUGAGGCCGAAAGGCCGAA ACUCUGU
209	1983	UUUCAGU CUGAUGAGGCCGAAAGGCCGAA AACUCUG
227	1984	CGCAAGG CUGAUGAGGCCGAAAGGCCGAA AGGCAUU
228	1985	CCGCAAG CUGAUGAGGCCGAAUAGGCCGA AAGGCAU
231	1986	UCACCGC CUGAUGAGGCCGAAAGGCCGAA AGGAAGG
247	1987	GUCUAGG CUGAUGAGGCCGAAAGGCCGAA AUUCGCU
248	1988	UGUCUAG CUGAUGAGGCCGAAAGGCCGAA AAUUCGC
251	1989	AGGUGUC CUGAUGAGGCCGAAAGGCCGUA AGGAAUU
292	1990	GUCGCAG CUGAUGAGGCCGAAAGGCCGAA AUUUGUG
308	1991	GAAGCCC CUGAUGAGGCCGAAAGGCCGAA AGGUUGG
314	1992	GGACCCG CUGAUGAGGCCGAAAGGCCGAA AGCCCUA
315	1993	UGGACCC CUGAUGAGGCCGAAAGGCCGAA AAGCCCU
320	1994	UCUGCUG CUGAUGAGGCCGAAAGGCCGAA ACCCGAA
337	1995	UGUUUCU CUGAUGAGGCCGAAAGGCCGAA AGGUGCC
353	1996	AGGUGCA CUGAUGAGGCCGAAAGGCCGAA AUGGUGU
381	1997	UCACUCG CUGAUGAGGCCGAAAGGCCGAA ACAGUGC
407	1998	GGUGCAG CUGAUGAGGCCGAAAGGCCGAA ACACAGC
418	1999	CGAGCAU CUGAUGAGGCCGAUAGGCCGAA AGCGGUG
424	2000	GCCGGGC CUGAUGAGGCCGAAAGGCCGAA AGCAUGA
433	2001	GACCCCA CUGAUGAGGCCGAAAGGCCGAA AGCCGGG
434	2002	UGACCCC CUGAUGAGGCCGAAAGGCCGAA AAGCCGG
440	2003	UCUGCUU CUGAUGAGGCCGAAAGGCCGAA ACCCCAA
449	2004	CUGUAGC CUGAUGAGGCCGAAAGGCCGAA AUCUGCU
453	2005	ACCCCUG CUGAUGAGGCCGAAAGGCCGAA AGCAAUC
461	2006	UAUCAGA CUGAUGAGGCCGAAAGGCCGAA ACCCCUG
462	2007	GUAUCAG CUGAUGAGGCCGAAAGGCCGAA AACCCCU
463	2008	GGUAUCA CUGAUGAGGCCGAAAGGCCGAA AAACCCC
468	2009	CAGAUGG CUGAUGAGGCCGAAAGGCCGAA AUCAGAA
473	2010	GCUCGCA CUGAUGAGGCCGAAAGGCCGAA AUGGUAU
491	2011	AGAAGCC CUGAUGAGGCCGAAAGGCCGAA ACUGGGC
496	2012	GGAGAAG CUGAUGAGGCCGAAAGGCCGAA AGCCGAC
497	2013	UGGAGAA CUGAUGAGGCCGAAAGGCCGAA AAGCCGA
499	2014	AUUGGAG CUGAUGAGGCCGAAAGGCCGAA AGAAGCC
500	2015	CAUUGGA CUGAUGAGGCCGAAAGGCCGAA AAGAAGC
502	2016	CACAUUG CUGAUGAGGCCGAAAGGCCGAA AGAAGAA
511	2017	AGCAGAU CUGAUGAGGCCGAAAGGCCGAA ACACAUU
514	2018	GAAAGCA CUGAUGAGGCCGAAAGGCCGAA AUGACAC
519	2019	UUUUCGA CUGAUGAGGCCGAAAGGCCGAA AGCAGAU
520	2020	UUUUUCG CUGAUGAGGCCGAAAGGCCGAA AAGCAGA
521	2021	AUUUUUC CUGAUGAGGCCGAAAGGCCGAA AAAGCAG
531	2022	CAAGGGU CUGAUGAGGCCGAAAGGCCGAA ACAUUUU
537	2023	CUUGUCC CUGAUGAGGCCGAAAGGCCGAA AGGGUGA
566	2024	GUUGCAC CUGAUGAGGCCGAAAGGCCGAA ACCAGGU
599	2025	CACAGAC CUGAUGAGGCCGAAAGGCCGAA ACAUCAG
602	2026	GACCACA CUGAUGAGGCCGAAAGGCCGAA ACAACAU
609	2027	UCCUGGG CUGAUGAGGCCGAAAGGCCGAA ACCACAG
618	2028	CUCAGCC CUGAUGAGGCCGAAAGGCCGAA AUCCUGG
641	2029	UGAUGGG CUGAUGAGGCCGAAAGGCCGAA AUCACCA
647	2030	CGAAGAU CUGAUGAGGCCGAAAGGCCGAA AUGGGGA
650	2031	UCCCGAA CUGAUGAGGCCGAAAGGCCGAA AUGAUGG
652	2032	GAUCCCG CUGAUGAGGCCGAAAGGCCGAA AGAUGAU
653	2033	GGAUCCC CUGAUGAGGCCGAAAGGCCGAA AAGAUGA
659	2034	CAAACAG CUGAUGAGGCCGAAAGGCCGAA AUCCCGA
664	2035	GAUGGCA CUGAUGAGGCCGAAAGGCCGAA ACAGGAU
665	2036	GGAUGGC CUGAUGAGGCCGAAAGGCCGAA AACAGGA
671	2037	CCAAGAG CUGAUGAGGCCGAAAGGCCGAA AUGGCAA
674	2038	GCACCAA CUGAUGAGGCCGAAAGGCCGAA AGGAUGG
676	2039	CAGCACC CUGAUGAGGCCGAAAGGCCGAA AGAGGAU
686	2040	UGAUAAA CUGAUGAGGCCGAAAGGCCGAA ACCAGCA
688	2041	UUUGAUA CUGAUGAGGCCGAAAGGCCGAA AGACCAG
689	2042	UUUUGAU CUGAUGAGGCCGAAAGGCCGAA AAGACCA
690	2043	UUUUUGA CUGAUGAGGCCGAAAGGCCGAA AAAGACC
692	2044	CCUUUUU CUGAUGAGGCCGAAAGGCCGAA AUAAAGA
720	2045	GGGGCCU CUGAUGAGGCCGAAAGGCCGAA AUUGGUU
755	2046	GAAAAUU CUGAUGAGGCCGAAAGGCCGAA AUCUCCU
759	2047	UCGGGAA CUGAUGAGGCCGAAAGGCCGAA AUUGAUC
760	2048	GUCGGGA CUGAUGAGGCCGAAAGGCCGAA AAUUGAU
762	2049	CGUCGGG CUGAUGAGGCCGAAAGCCCGAA AAAUUGA
762	2050	UCGUCGG CUGAUGAGGCCGAAAGGCCGAA AAAAUUG
772	2051	CCAGGAA CUGAUGAGGCCGAAAGGCCGAA AUCGUCG
773	2052	AGCCAGG CUGAUGAGGCCGAAAGGCCGAA AGAUCGU
774	2053	GAGCCAG CUGAUGAGGCCGAAAGGCCGAA AAGAUCG
781	2054	AGUGUUG CUGAUGAGGCCGAAAGGCCGAA AGCCAGG
795	2055	UGCACUG CUGAUGAGGCCGAAAGGCCGAA AGCAGCA
810	2056	CCAUGUA CUGAUGAGGCCGAAAGGCCGAA AGUCUCC
822	2057	UCCAUGUC UGAUGAGGCCGAAAGGCCGAA AAGUCUC
822	2058	AUCCAUG CUGAUGAGGCCGAAAGGCCGAA AAAGUCU
830	2059	CCUGGGU CUGAUGAGGCCGAAAGGCCGAA ACCGGUU
855	2060	GAGAUGC CUGAUGAGGCCGAAAGGCCGAA ACUCUCU
860	2061	GCACUGA CUGAUGAGGCCGAAAGGCCGAA AUGCGAC
862	2062	CUGCACU CUGAUGAGGCCGAAAGGCCGAA AGAUGCG
927	2063	UCUGGCC CUGAUGAGGCCGAAAGGCCGAA ACUGCCU
981	2064	CUGGGCA CUGAUGAGGCCGAAAGGCCGAA AGCUCCC
990	2065	UGGCACU CUGAUGAGGCCGAAAGGCCGAA ACUGGGC

[0096]

TABLE XII
Mouse CD40 Hammerhead Ribozyme Target Sequences
nt.		HH Target	nt.		HH Target
Position	SEQ ID NO	Sequence	Position	SEQ ID NO	Sequence
18	927	GGUgucU u UGCCUCg	479	973	cAUCAcU U UUCgaaA
18	927	GGuguCU u UGCCucG	480	974	AUCacuU U UCGAAAA
24	928	UuUGCCU C gGCuGUG	481	975	UCacuUU U CGAAAAg
38	929	GCGcgCU a UGGGGCU	481	975	UCACuuU U cGAaAAG
62	930	CagcGGU c CaUCUag	492	976	AAAgUGU u AuCCcUG
62	930	CaGCgGU C CAUCuAG	560	977	CUaAUGU c aUCUGUG
66	931	gGUCCAU C uAGggCa	563	978	AUGUcaU C UGUGGUu
80	932	AGUGuGU u acgUGca	572	979	gUGGUuU a AagUCcC
80	932	AgUGUGU u AcgUGCa	572	979	GuGGUUU a aagUcCC
81	933	gUGugUU a CgUGGaG	577	980	UuAAagU c CCgGAuG
100	934	AAACAGU A CCUccac	620	981	UGGgcAU C CuCAUCA
126	935	CUGUgaU U UGUGCCA	626	982	UCCuCAU C AcCaUuu
127	936	UGUgaUU U GUGCCAG	632	983	uCAcCAU u UUCGGGg
170	937	CAgcUcU u gaGAaGA	632	983	UcaCCAU u uUCggGG
208	938	gGCGAAU U CucAGcC	634	984	AcCAUuU U CGGGgUg
209	939	GCGAAUU C ucAGcCc	635	985	CCaUuuU c GgGGUGu
233	940	gGGAGAU u cgcUgUC	635	985	cCAUuUU C GGGgUgu
267	941	ACCcAAU c AAggGcu	635	985	CCAUuuU C ggGGUGu
267	941	AcCCAAU c AaGggCu	647	986	UGuUucU C UaUAUCA
275	942	aAGGGCU U CGGGUua	649	987	uUucUCU a UAUCAAA
275	942	AaGGGcU U CgGgUua	651	988	ucUCUaU A UCAAAAA
276	943	AGGGCUU C GGGUuaA	653	989	UCUaUAU C AAAAAGG
281	944	UUCGGGU u aAGaAGg	735	990	gGAaGAU u aUCCcGG
281	944	UUcGGGU u AAGaAGg	759	991	cGCUGCU C CAGUGGA
314	945	ACACugU C UGuACCU	794	992	AgCCuGU C ACaCAGG
354	946	caAgGaU u GCgaGGC	794	992	AGcCuGU c acaCAGg
386	947	cCugUaU c CCUGGCU	819	878	AGAGAGU C GCAUCUC
394	948	CCUgGCU u uGGaGuu	824	879	GUCGCAU C UCAGUGC
394	948	CCuGGCU U UGGaGUu	826	880	CGCAUCU C AGUGCAG
395	949	CuGGCUU U GGaGUuA	876	993	cCCUGGU C UgAaCcC
429	950	caCUGAU A CCgUCUG	913	832	GGCUGCU U GCUGACC
434	951	AUACCgU C UGucAUC	997	994	CUCAaCU u GCuuUuu
434	951	AUaCcGU c UGuCAUC	1003	995	uUGCUUU u uAAggAU
441	952	CugUCaU C CcuGCcC	1003	995	uugCUUU u uAaGGAU
452	892	GCCCAGU C GGCUUCU	1023	996	gaAAgCU c GGGCaUC
452	892	GCCCAGU C gGcuuCu	1048	997	CAGuGaU a UCUaccA
457	893	GUCGGCU U CUUCUCC	1052	998	gAUauCU a CCaaGuG
458	894	UCGGCUU C UUCUCCA	1081	999	CCAGagU u GuCUugc
460	895	GGCUUCU U CUCCAAU	1084	1000	gAGUuGU C uUGCuGC
461	953	GCUUCUU C UCCAAUc	1086	1001	gUugUCU U GcUGCgG
463	954	UUCUUCU C CAAUcaG	1097	1002	gCgGcGU U CACUGuA
472	955	AAuCAGU C AucaCUu	1098	1003	CgGcGUU C ACUGuAA
472	955	AAUcagU c auCACuU	1118	956	cgUgGCU A CAGGaGU
1118	956	CgUGGCU a CAggAgU
1141	957	CgCaGCU u gUGCUCG
1164	958	aCCUGgU U GCCAUCa
1202	959	UGuaaUU a UUUaUaC
1220	960	gGcAuCU c AgAAACu
1220	960	GGCAuCU C AGAAACu
1228	961	aGAaACU c UAgcaGG
1253	962	AaCaGGU a GUGgAAu
1331	963	AGgAGcU U GCUgCcc
1362	964	uUuUGaU C CCugGGA
1373	965	gGGaCUU c AUgguAA
1373	965	GgGACUU c AugguaA
1413	966	uUGUCAU u UGaccUC
1443	967	GUaaUGU a CcccGUG
1470	968	CACAuAU c CUaaaAu
1492	969	GugGUGU a uUGuAga
1497	970	GuAuUGU A gaAaUuA
1508	971	auUauUU a aUCcGCC
1508	971	AUuAuUU a auCCGcC
1523	972	cuGGGuU u CUaccUG

[0097]

TABLE XIII
Mouse CD40 Hammerhead Ribozyme Sequences
nt.	SEQ
Posi-	ID
tion	NO	HH Ribozyme Sequence
18	2066	CGAGGCA CUGAUGAGGCCGAAAGGCCGAA AGACACC
18	2066	CGAGGCA CUGAUGAGGCCGAAAGGCCGAA AGACACC
24	2067	CACAGCC CUGAUGAGGCCGAAAGGCCGAA AGGCAAA
38	2068	AGCCCCA CUGAUGAGGCCGAAAGGCCGAA AGCGCGC
62	2069	CUAGAUG CUGAUGAGGCCGAAAGGCCGAA ACCGCUG
62	2069	CUAGAUG CUGAUGAGGCCGAAAGGCCGAA ACCGCUG
66	2070	UGCCCUA CUGAUGAGGCCGAAAGGCCGAA AUGGACC
80	2071	UGCACGU CUGAUGAGGCCGAAAGGCCGAA ACACACU
80	2071	UGCACGU CUGAUGAGGCCGAAAGGCCGAA ACACACU
81	2072	CUGCACG CUGAUGAGGCCGAAAGGCCGAA AACACAC
100	2073	GUGGAGG CUGAUGAGGCCGAAAGGCCGAA ACUGUUU
126	2074	UGGCACA CUGAUGAGGCCGAAAGGCCGAA AUCACAG
127	2075	CUGGCAC CUGAUGAGGCCGAAAGGCCGAA AAUCACA
170	2076	UCUUCUC CUGAUGAGGCCGAAAGGCCGAA AGAGCUG
208	2077	GGCUGAG CUGAUGAGGCCGAAAGGCCGAA ATUCGCC
209	2078	GGGCUGA CUGAUGAGGCCGAAAGGCCGAA AAUUCGC
233	2079	GACAGCG CUGAUGAGGCCGAAAGGCCGAA AUCUCCC
267	2080	AGCCCUU CUGAUGAGGCCGAAAGGCCGAA AUUGGGU
267	2080	AGCCCUU CUGAUGAGGCCGAAAGGCCGAA AUUGGGU
275	2081	UAACCCG CUGAUGAGGCCGAAAGGCCGAA AGCCCUU
275	2081	UAACCCG CUGAUGAGGCCGAAAGGCCGAA AGCCCUU
276	2082	UUAACCC CUGAUGAGGCCGAAAGGCCGAA AAGCCCU
281	2083	CCUUCUU CUGAUGAGGCCGAAAGGCCGAA ACCCGAA
281	2083	CCUUCUU CUGAUGAGGCCGAAAGGCCGAA ACCCGAA
314	2084	AGGUACA CUGAUGAGGCCGAAAGGCCGAA ACAGUGU
354	2085	GCCUCGC CUGAUGAGGCCGAAAGGCCGAA AUCCUUG
386	2086	AGCCAGG CUGAUGAGGCCGAAAGGCCGAA AUACAGG
394	2087	AACUCCA CUGAUGAGGCCGAAAGGCCGAA AGCCAGG
394	2087	AACUCCA CUGAUGAGGCCGAAAGGCCGAA AGCCAGG
395	2088	UAACUCC CUGAUGAGGCCGAAAGGCCGAA AAGCCAG
429	2089	CAGACGG CUGAUGAGGCCGAAAGGCCGAA AUCAGUG
434	2090	GAUGACA CUGAUGAGGCCGAAAGGCCGAA ACGGUAU
434	2090	GAUGACA CUGAUGAGGCCGAAAGGCCGAA ACGGUAU
441	2091	GGGCAGG CUGAUGAGGCCGAAAGGCCGAA AUGACAG
452	2011	AGAAGCC CUGAUGAGGCCGAAAGGCCGAA ACUGGGC
452	2011	AGAAGCC CUGAUGAGGCCGAAAGGCCGAA ACUGGGC
457	2012	GGAGAAG CUGAUGAGGCCGAAAGGCCGAA AGCCGAC
458	2013	UGGAGAA CUGAUGAGGCCGAAAGGCCGAU AAGCCGA
460	2014	AUUGGAG CUGAUQAGGCCGAAAGGCCGAA AGAAGCC
461	2092	GAUUGGA CUGAUGAGGCCGAAAGGCCGAA AAGAAGC
463	2093	CUGAUUG CUGAUGAGGCCGAAAGGCCGAA AGAAGAA
472	2094	AAGUGAU CUGAUGAGGCCGAAAGGCCGAA ACUGAUU
472	2094	AAGUGAU CUGAUGAGGCCGAAAGGCCGAA ACUGAUU
479	2095	UUUCGAA CUGAUGAGGCCGAAAGGCCGAA AGUGAUG
480	2096	UUUUCGA CUGAUGAGGCCGAAAGGCCGAA AAGUGAU
481	2097	CUUUUCG CUGAUGAGGCCGAAAGGCCGAA AAAGUGA
481	2097	CUUUUCG CUGAUGAGGCCGAAAGGCCGAA AAAGUGA
492	2098	CAGGGAU CUGAUGAGGCCGAAAGGCCGAA ACACUUU
560	2099	CACAGAU CUGAUGAGGCCGAAAGGCCGAA ACAUUAG
563	2100	AACCACA CUGAUGAGGCCGAAAGGCCGAA AUGACAU
572	2101	GGGACUU CUGAUGAGGCCGAAAGGCCGAA AAACCAC
572	2101	GGGACUU CUGAUGAGGCCGAAAGGCCGAA AAACCAC
577	2102	CAUCCGG CUGAUGAGGCCGAAAGGCCGAA ACUUUAA
620	2103	UGAUGAG CUGAUGAGGCCGAAAGGCCGAA AUGCCCA
626	2104	AAAUGGU CUGAUGAGGCCGAAAGGCCGAA AUGAGGA
632	2105	CCCCGAA CUGAUGAGGCCGAAAGGCCGAA AUGGUGA
632	2105	CCCCGAA CUGAUGAGGCCGAAAGGCCGAA AUGGUGA
634	2106	CACCCCG CUGAUGAGGCCGAAAGGCCGAA AAAUGGU
635	2107	ACACCCC CUGAUGAGGCCGAAAGGCCGAA AAAAUGG
635	2107	ACACCCC CUGAUGAGGCCGAAAGGCCGAA AAAAUGG
635	2107	ACACCCC CUGAUGAGGCCGAAAGGCCGAA AAAAUGG
647	2108	UGAUAUA CUGAUGAGGCCGAAAGGCCGAA AGAAACA
649	2109	UUUGAUA CUGAUGAGGCCGAAAGGCCGAA AGAGAAA
651	2110	UUUUUGA CUGAUGAGGCCGAAAGGCCGAA AUAGAGA
653	2111	CCUTUUU CUGAUGAGGCCGAAAGGCCGAA AUAUAGA
735	2112	CCGGGAU CUGAUGAGGCCGAAAGGCCGAA AUCUUCC
759	2113	UGCACUG CUGAUGAGGCCGAAAGGCCGAA AGCAGCG
794	2114	CCUGUGU CUGAUGAGGCCGAAAGGCCGAA ACAGGCU
794	2114	CCUGUGU CUGAUGAGGCCGAAAGGCCGAA ACAGGCU
819	2060	GAGAUGC CUGAUGAGGCCGAAAGGCCGAA ACUCUCU
824	2061	GCACUGA CUGAUGAGGCCGAAAGGCCGAA AUGCGAC
826	2062	CUGCACU CUGAUGAGGCCGAAAGGCCGAA AGAUGCG
876	2115	GGGUUCA CUGAUGAGGCCGAAAGGCCGAA ACCAGGG
913	1971	GGUCAGC CUGAUGAGGCCGAAAGGCCGAA AGCAGCC
997	2116	AAAAAGC CUGAUGAGGCCGAAAGGCCGAA AGUUGAG
1003	2117	AUCCUUA CUGAUGAGGCCGAAAGGCCGAA AAAGCAA
1003	2117	AUCCUUA CUGAUGAGGCCGAAAGGCCGAA AAAGCAA
1023	2118	GAUGCCC CUGAUGAGGCCGAAAGGCCGAA AGCUUUC
1048	2119	UGGUAGA CUGAUGAGGCCGAAAGGCCGAA AUCACUG
1052	2120	CACTUGG CUGAUGAGGCCGAAAGGCCGAA AGAUAUC
1081	2121	GCAAGAC CUGAUGAGGCCGAAAGGCCGAA ACUCUGG
1084	2122	GCAGCAA CUGAUGAGGCCGAAAGGCCGAA ACAACUC
1086	2123	CCGCAGC CUGAUGAGGCCGAAAGGCCGAA AGACAAC
1097	2124	UACAGUG CUGAUGAGGCCGAAAGGCCGAA ACGCCGC
1098	2125	UUACAGU CUGAUGAGGCCGAAAGGCCGAA AACGCCG
1118	2126	ACUCCUG CUGAUGAGGCCGAAAGGCCGAA AGCCACG
1118	2126	ACUCCUG CUGAUGAGGCCGAAAGGCCGAA AGCCACG
1141	2127	CGAGCAC CUGAUGAGGCCGAAAGGCCGAA AGCUGCG
1164	2128	UGAUGGC CUGAUGAGGCCGAAAGGCCGAA ACCAGGU
1202	2129	GUAUAAA CUGAUGAGGCCGAAAGGCCGAA AAUUACA
1220	2130	AGUUUCU CUGAUGAGGCCGAAAGGCCGAA AGAUGCC
1220	2130	AGUUUCU CUGAUGAGGCCGAAAGGCCGAA AGAUGCC
1228	2131	CCUGCUA CUGAUGAGGCCGAAGGCCGAAA AGUUUCU
1253	2132	AUUCCAC CUGAUGAGGCCGAAAGGCCGUA ACCUGUU
1331	2133	GGGCAGC CUGAUGAGGCCGAAAGGCCGAA AGCUCCU
1362	2134	UCCCAGG CUGAUGAGGCCGAAAGGCCGAA AUCAAAA
1373	2135	UUACCAU CUGAUGAGGCCGAAAGGCCGAA AAGUCCC
1373	2135	UUACCAU CUGAUGAGGCCGAAAGGCCGAA AAGUCCC
1413	2136	GAGGUCA CUGAUGAGGCCGAAAGGCCGAA AUGACAA
1443	2137	CACGGGG CUGAUGAGGCCGAAAGGCCGAA ACAUUAC
1470	2138	AUUUUAG CUGAUGAGGCCGAAAGGCCGAA AUAUGUG
1492	2139	UCUACAA CUGAUGAGGCCGAAAGGCCGAA ACACCAC
1497	2140	UAAUUUC CUGAUGAGGCCGAAAGGCCGAA ACAAUAC
1508	2141	GGCGGAU CUGAUGAGGCCGAAAGGCGAUA AAAUAAU
1508	2141	GGCGGAU CUGAUGAGGCCGAAAGGCCGAA AAAUAAU
1523	2142	CAGGUAG CUGAUGAGGCCGAAAGGCCGAA AACCCAG

[0098]

TABLE XIV
Human B7 Hairpin Ribozyme and Target Sequence
nt.	SEQ ID		SEQ ID
Position	NO	Hairpin Ribozyme Sequence	NO	Substrate
286	2143	ACAGGCAG AGAA GAUGAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1004	GUCAUCA GCC CUGCCUGU
291	2144	GCAAAACA AGAA GGGCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1005	CAGCCCU GCC UGUUUUGC
295	2145	AGGUGCAA AGAA GGCAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1006	CCUGCCU GUU UUGCACCU
437	2146	GCACCAAG AGAA GAAAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1007	UCUUUCA GCU CUUGGUGC
469	2147	AACACCUG AGAA GAAGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1008	CACUUCU GUU CAGGUGUU
518	2148	GACCACAG AGAA GCGUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1009	CAACGCU GUC CUGUGGUC
540	2149	AGCUCUUC AGAA GAAACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1010	UGUUUCU GUU GAAGAGCU
596	2150	ACAUCAUA AGAA GCACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1011	UGGUGCU GAC UAUGAUGU
644	2151	CAAAGAUG AGAA GGUUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1012	AGAACCG GAC CAUCUUUG
702	2152	GUGCCCUC AGAA GAUGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1013	CCCAUCU GAC GAGGGCAC
795	2153	GUAGGGAA AGAA GCUUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1014	CAAAGCU GAC UUCCCUAC
819	2154	AUUUCAAA AGAA GAUAUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1015	UAUAUCU GAC UUUGAAAU
939	2155	UCUUGGGA AGAA GUUGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1016	CACAACA GUU UCCCAAGA
1012	2156	ACACAUGA AGAA GUGGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1017	AACCACA GCU UCAUGUGU
1055	2157	AGUUGAAG AGAA GAUUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1018	UGAAUCA GAC CUUCAACU
1103	2158	AGGAUGGG AGAA GGUUAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1019	AUAACCU GCU CCCAUCCU
1159	2159	GUAGGUCA AGAA GCAUAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1020	AUAUGCU GCC UGACCUAC
1163	2160	AGCAGUAG AGAA GGCAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1021	GCUGCCU GAC CUACUGCU
1171	2161	UGGGGCAA AGAA GUAGGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1022	ACCUACU GCU UUGCCCCA
1356	2162	GUGGGUAA AGAA GCUUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1023	UUAAGCU GUU UUACCCAC
1395	2163	UCAGCUUA AGAA GAAAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1024	UCUUUCA GAU UAAGCUGA

[0099]

TABLE XV
Mouse B7 Hairpin Ribozyme and Target Sequence
nt.	SEQ ID		SEQ ID
Position	NO	Hairpin Ribozyme Sequence	NO	Substrate
74	2164	AGAAAUGG AGAA GAGUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1025	ACACUCU GUU CCAUUUCU
114	2165	AUCCACCC AGAA GAUGCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1026	AGCAUCU GCC GGGUGGAU
154	2166	AAUCGAGA AGAA GAGAUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1027	CAUCUCU GUU UCUCGAUU
265	2167	CCUGCAUC AGAA GACAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1028	AUUGUCA GUU GAUGCAGG
328	2168	GACGAAUC AGAA GCACAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1029	UUGUGCU GCU GAUUCGUC
331	2169	AAAGACGA AGAA GCAGCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1030	UGCUGCU GAU UCGUCUUU
356	2170	UCAUCAAC AGAA GAAGAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1031	GUCUUCA GAU GUUGAUGA
373	2171	CUGACUUG AGAA GUUGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1032	AACAACU GUC CAAGUCAG
403	2172	AACGGCAA AGAA GCAAUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1033	UAUUGCU GCC UUGCCGUU
481	2173	CAAUGACA AGAA GCACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1034	UGGUGCU GUC UGUCAUUG
529	2174	CAUAUAAA AGAA GGUUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1035	AGAACCG GAC UUUAUAUG
584	2175	GUGCCCCG AGAA GAAAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1036	CCUUUCA GAC CGGGGCAC
600	2176	AACGACAC AGAA GUAUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1037	ACAUACA GCU GUGUCGUU
677	2177	GUAGAGAA AGAA GCUUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1038	CAAAGCU GAC UUCUCUAC
741	2178	GGAAGCAA AGAA GGUAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1039	AUUACCU GCU UUGCUUCC
1028	2179	AUGACGAC AGAA GUUAUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1040	AAUAACA GUC GUCGUCAU
1077	2180	UCUUCUGA AGAA GCUUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1041	AGAAGCU GUU UCAGAAGA
1116	2181	GAAGGUAA AGAA GUUGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1042	AACAACA GCC UUACCUUC
1153	2182	GGAAGACG AGAA GUUCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1043	CUGAACA GAC CGUCUUCC
1157	2183	UAAAGGAA AGAA GUCUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1044	ACAGACC GUC UUCCUUUA
1178	2184	CCCACAUG AGAA GAGAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1045	CUUCUCU GUC CAUGUGGG
1246	2185	UCCGAAAG AGAA GCUAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1046	GCUAGCU GAU CUUUCGGA
1523	2186	CAGAAAAG AGAA GGCCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1047	GAGGCCU GCC CUUUUCUG

[0100]

TABLE XVI
Human B7-2 Hairpin Ribozyme and Target Sequences
nt.	SEQ ID		SEQ ID
Position	NO	HP Ribozyme Sequences	NO	Substrate
25	2187	GUUACAGC AGAA GAGAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1048	CUUCUCU GCU GCUGUAAC
28	2188	CCUGUUAC AGAA GCAGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1049	CUCUGCU GCU GUAACAGG
57	2189	CCCCACUC AGAA GUGUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1050	ACACACG GAU GAGUGGGG
162	2190	CACCAGAG AGAA GGAAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1051	CCUUCCU GCU CUCUGGUG
175	2191	UUCAGAGG AGAA GCACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1052	UGGUGCU GCU CCUCUGAA
214	2192	CAUGGCAG AGAA GCAGUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1053	GACUGCA GAC CUGCCAUG
380	2193	CAGGGUCC AGAA GUCCGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1054	UCGGACA GUU GGACCCUG
408	2194	UGUCCUUG AGAA GAAGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1055	AUCUUCA GAU CAAGGACA
480	2195	CAGAAUUC AGAA GGUGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1056	UCCACCA GAU GAAUUCUG
575	2196	UAUAGAUG AGAA GGUCAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1057	UUGACCU GCU CAUCUAUA
710	2197	AACAGACA AGAA GAUGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1058	UCCAUCA GCU UGUCUGUU
718	2198	GGGAAUGA AGAA GACAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1059	CUUGUCU GUU UCAUUCCC
730	2199	CUCGUAAC AGAA GGGAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1060	AUUCCCU GAU GUUACGAG
783	2200	AAGAUAAA AGAA GCGUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1061	AGACGCG GCU UUUAUCUU
825	2201	CUGGGGGA AGAA GAGGGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1062	ACCCUCA GCC UCCCCCAG
835	2202	GGAAUGUG AGAA GGGGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1063	UCCCCCA GAC CACAUUCC
856	2203	GGAAGUAC AGAA GUAAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1064	GAUUACA GCU GUACUUCC
896	2204	UAGAAUUA AGAA GAAAAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1065	GUUUUCU GUC UAAUUCUA
930	2205	AGUUGCGA AGAA GCUUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1066	AGAAGCG GCC UCGCAACU
987	2206	UUUUCUUG AGAA GUUCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1067	GUGAACA GAC CAAGAAAA
1027	2207	UGGGCUUC AGAA GAUCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1068	AAGAUCU GAU GAAGCCCA

[0101]

TABLE XVII
Mouse B7-2 Hairpin Ribozyme and Target Sequences
nt.	SEQ ID		SEQ ID
Position	NO	HP Ribozyme Sequences	NO	Substrate
10	2208	UCUUACGC AGAA GCUUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1069	GCAAGCA GAC GCGUAAGA
42	2209	UUGUUCAA AGAA GUGCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1070	CAGCACG GAC UUGAACAA
56	2210	CUACAGGA AGAA GGUUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1071	ACAACCA GAG UCCUGUAG
108	2211	CAUGGUGC AGAA GGGGUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1072	GACCCCA GAU GCACCAUG
146	2212	AUCAGCAA AGAA GUCACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1073	UGUGACA GUC UUGCUGAU
154	2213	CAUCUGAG AGAA GCAAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1074	UCUUGCU GAU CUCAGAUG
161	2214	GAAACAGC AGAA GAGAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1075	GAUCUCA GAU GCUGUUUC
167	2215	UCCACGGA AGAA GCAUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1076	AGAUGCU GUU UCCGUGGA
211	2216	AUGGGCAC AGAA GAUAUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1077	CAUAUCU GCC GUGCCCAU
400	2217	UGUCCUUG AGAA GAACAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1078	AUGUUCA GAU CAAGGACA
679	2218	AGAUACUG AGAA GUUCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1079	CAGAACU GUU CAGUAUCU
696	2219	AAGAGAGA AGAA GUUGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1080	UCCAACA GCC UCUCUCUU
716	2220	CACACACC AGAA GGGAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1081	AUUCCCG GAU GGUGUGUG
737	2221	ACACACAC AGAA GUCAUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1082	UAUGACC GUU GUGUGUGU
839	2222	GUAACUGA AGAA GUAAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1083	GAUUACA GCU UCAGUUAC
874	2223	CAAUGAUG AGAA GCAUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1084	UGAUGCU GCU CAUCAUUG
907	2224	GCCUGCUA AGAA GAUUCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1085	CGAAUCA GCC UAGCAGGC
929	2225	AACUUAGA AGAA GUGUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1086	CAACACA GCC UCUAAGUU
1115	2226	UUCCAAUC AGAA GAGAAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1087	GUUCUCA GCU GAUUGGAA
1118	2227	GAAUUCCA AGAA GCUGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1088	CUCAGCU GAU UGGAAUUC
1133	2228	AAUUAUUC AGAA GUAGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1089	UUCUACA GUU GAAUAAUU

[0102]

TABLE XVIII
Human CD40 Hairpin Ribozyme and Target Sequences
nt.	SEQ ID		SEQ ID
Position	NO	Hairpin Ribozyme Sequences	NO	Substrate
26	2229	GACCAGGC AGAA GGACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1090	UGGUCCU GCC GCCUGGUC
29	2230	UGAGACCA AGAA GCAGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1091	UCCUGCC GCC UGGUCUCA
58	2231	ACUGCAGA AGAA GACGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1092	UUCGUCU GCC UCUGCAGU
84	2232	GGUCAGCA AGAA GCCCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1093	UGGGGCU GCU UGCUGACC
91	2233	GGACAGCG AGAA GCAAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1094	GCUUGCU GAC CGCUGUCC
95	2234	GGAUGGAC AGAA GUCAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1095	GCUGACC GCU GUCCAUCC
98	2235	UCUGGAUG AGAA GCGGUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1096	GACCGCU GUC CAUCCAGA
159	2236	GCACAAAG AGAA GCACUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1097	CAGUGCU GUU CUUUGUGC
414	2237	CGAGCAUG AGAA GUGCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1098	CUGCACC GCU CAUGCUCG
429	2238	GACCCCAA AGAA GGGCGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1099	UCGCCCG GCU UUGGGGUC
445	2239	CUGUAGCA AGAA GCUUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1100	UCAAGCA GAU UGCUACAG
483	2240	GCCGACUG AGAA GGGCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1101	GAGCCCU GCC CAGUCGGC
488	2241	AAGAAGCC AGAA GGGCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1102	CUGCCCA GUC GGCUUCUU
492	2242	GGAGAAGA AGAA GACUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1103	CCAGUCG GCU UCUUCUCC
515	2243	UUUUCGAA AGAA GAUGAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1104	GUCAUCU GCU UUCGAAAA
593	2244	CAGACAAC AGAA GUCUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1105	CAAGACU GAU GUUGUCUG
619	2245	GGGCUCUC AGAA GAUCCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1106	AGGAUCG GCU GAGAGCCC
661	2246	GGAUGGCA AGAA GGAUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1107	GGAUCCU GUU UGCCAUCC
764	2247	GGAAGAUC AGAA GGAAAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1108	UUUUCCC GAC GAUCUUCC
788	2248	ACUGGAGC AGAA GUGUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1109	CAACACU GCU GCUCCAGU
791	2249	UGCACUGG AGAA GCAGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1110	CACUGCU GCU CCAGUGCA
924	2250	CUCUGGCC AGAA GCCUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1111	ACAGGCA GUU GGCCAGAG
946	2251	CCUGCAGC AGAA GCACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1112	UGGUGCU GCU GCUGCAGG
949	2252	ACCCCUGC AGAA GCAGCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1113	UGCUGCU GCU GCAGGGGU

[0103]

TABLE XIX
Mouse CD40 Hairpin Ribozyme and Substrate Sequences
nt.	SEQ ID		SEQ ID
Position	NO	HP Ribozyme Sequences	NO	Substrate
25	2253	GCGCGCAC AGAA GAGGCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1114	UGCCUCG GCU GUGCGCGC
45	2254	UGUCAACA AGAA GCCCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1115	UGGGGCU GCU UGUUGACA
59	2255	CCUAGAUG AGAA GCUGUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1116	GACAGCG GUC CAUCUAGG
144	2256	GCUUGUCA AGAA GCUUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1117	GGAAGCC GAC UGACAAGC
164	2257	UUCUCAAG AGAA GUGCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1118	CUGCACA GCU CUUGAGAA
212	2258	UUCCACUG AGAA GAGAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1119	AUUCUCA GCC CAGUGGAA
311	2259	CAGGUACA AGAA GUGUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1120	AGACACU GUC UGUACCUG
431	2260	GGAUGACA AGAA GUAUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1121	UGAUACC GUC UGUCAUCC
444	2261	GCCGACUG AGAA GGGAUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1122	CAUCCCU GCC CAGUCGGC
449	2241	AAGAAGCC AGAA GGGCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1102	CUGCCCA GUC GGCUUCUU
453	2242	GGAGAAGA AGAA GACUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1103	CCAGUCG GCU UCUUCUCC
550	2262	UGACAUUA AGAA GACUCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1123	CGAGUCA GAC UAAUGUCA
580	2263	GGGCUCGC AGAA GGGACU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1124	AGUCCCG GAU GCGAGCCC
592	2264	GAAUGACC AGAA GGGCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1125	GAGCCCU GCU GGUCAUUC
605	2265	CCCAUCAC AGAA GGAAUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1126	CAUUCCU GUC GUGAUGGG
701	2266	UGCCGUCG AGAA GCAGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1127	CCCUGCG GCU CGACGGCA
752	2267	ACUGGAGC AGAA GUGUUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1128	UAACACC GCU GCUCCAGU
755	2268	UGCACUGG AGAA GCGGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1129	CACCGCU GCU CCAGUGCA
787	2269	GUGUGACA AGAA GACACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1130	GGUGUCA GCC UGUCACAC
890	2270	CCUCCAAA AGAA GUUCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1131	UGGAACU GCU UUUGGAGG
909	2271	GGUCAGCA AGAA GCCAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1132	GAUGGCU GCU UGCUGACC
916	2272	UUCAAAAG AGAA GCAAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1133	GCUUGCU GAC CUUUUGAA
975	2273	UGACAGGG AGAA GGCAUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1134	CAUGCCU GCC CCCUGUCA
1137	2274	CGAGCACA AGAA GCGGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1135	GCCCGCA GCU UGUGCUCG
1276	2275	GUUUUAAA AGAA GUUUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1136	AGAAACA GCU UUUAAAAC
1334	2276	CGGGUUUG AGAA GCAAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1137	GCUUGCU GCC CAAACCCG
1352	2277	GGAUCAAA AGAA GGUAAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1138	GUUACCU GAU UUUGAUCC
1512	2278	AAACCCAG AGAA GAUUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	1139	UUAAUCC GCC CUGGGUUU

[0104]

Claims

1. A nucleic acid molecule which inhibits synthesis and/or expression of an mRNA encoding B7-2.

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

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

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

5. The enzymatic nucleic acid of claim 2, wherein said enzymatic nucleic acid comprises between 12 and 100 bases complementary to the RNA of said region.

6. The enzymatic nucleic acid of claim 5, wherein said enzymatic nucleic acid comprises between 14 and 24 bases complementary to the RNA of said region.

7. A mammalian cell including an enzymatic nucleic acid molecule of claim 1.

8. A mammalian cell including an enzymatic nucleic acid molecule of claim 1.

9. The cell of claim 7, wherein said cell is a human cell.

10. The cell of claim 8, wherein said cell is a human cell

11. An expression vector comprising a nucleic acid encoding the enzymatic nucleic acid molecule of claim 2 in a manner which allows expression and/or delivery of the enzymatic nucleic acid molecule within a mammalian cell.

12. A mammalian cell including an expression vector of claim 11.

13. The cell of claim 10, wherein said cell is a human cell.

14. A method for the treatment of a subject having a condition associated with the level of B7-2, wherein the subject is administered a therapeutically effective amount of an enzymatic nucleic acid molecule of claim 1.

15. A method for the treatment of a subject having a condition associated with the level of B7-2, wherein the subject is administered a therapeutically effective amount of an enzymatic nucleic acid molecule of claim 2.

16. A method for the treatment of a subject having a condition associated with the level of B7-2 activity, wherein the subject is administered a therapeutically effective amount of the expression vector of claim 11.

17. The method of claim 14, wherein said subject is a human.

18. The method of claim 15, wherein said subject is a human.

19. The method of claim 16, wherein said subject is a human.

20. A method for inducing tolerance in a recipient to alloantigen of a donor comprising treating antigen presenting cells from a donor with nucleic acid of claim 1, and infusion of said treated antigen presenting cells into said recipient.

21. A method for inducing tolerance in a recipient to alloantigen of a donor comprising treating antigen presenting cells from a donor with nucleic acid of claim 2, and infusion of said treated antigen presenting cells into said recipient.

22. A method for enhancing graft tolerance comprising contacting a nucleic acid of claim 1 with cells of said graft prior to transplantation.

23. A method for enhancing graft tolerance comprising contacting a nucleic acid of claim 2 with cells of said graft prior to transplantation.

24. A method for treatment of an autoimmune disease, comprising contacting an antigen presenting cell of a patient with a nucleic acid of claim 1.

25. A method for treatment of an autoimmune disease, comprising contacting an antigen presenting cell of a patient with a nucleic acid of claim 2.

26. The method of claim 24, wherein said cells are contacted ex vivo with said nucleic acid.

27. The method of claim 25, wherein said cells are contacted ex vivo with said nucleic acid.

28. The method of claim 24, wherein said cells are contacted with autoantigen characteristic of said disease.

29. The method of claim 25, wherein said cells are contacted with autoantigen characteristic of said disease.

30. The method of claim 28, wherein said cells are reinfused into said patient.

31. The method of claim 29, wherein said cells are reinfused into said patient.

32. A method for the treatment of a subject having a condition associated with the level of B7-2, wherein said treatment involves tissue and/or cell donation to a subject, wherein the tissue donor, donated tissue, and/or corresponding cells is administered a therapeutically effective amount of an enzymatic nucleic acid molecule of claim 1.

33. A method for the treatment of a subject having a condition associated with the level of B7-2, wherein said treatment involves tissue and/or cell donation to a subject, wherein the tissue donor, donated tissue, and/or corresponding cells is administered a therapeutically effective amount of an enzymatic nucleic acid molecule of claim 2.