US20030003469A1

US20030003469A1 - Ribozyme treatment of diseases or conditions related to levels of NF-kappaB

Info

Publication number: US20030003469A1
Application number: US10/056,414
Authority: US
Inventors: Dan Stinchcomb; Kenneth Draper; James McSwiggen
Original assignee: Ribozyme Pharmaceuticals Inc
Current assignee: Sirna Therapeutics Inc
Priority date: 1992-12-07
Filing date: 2002-01-23
Publication date: 2003-01-02
Also published as: US6410224B1; US5658780A

Abstract

Enzymatic RNA molecules which cleave rel A mRNA.

Description

RELATED APPLICATIONS

This application is a continuation-in-part of 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 which is a continuation-in-part of Draper, “Method and Reagent for Treatment of a Stenotic Condition”, filed Dec. 7, 1992, U.S. Ser. No. 07/987,132, both hereby incorporated by reference herein.[0001]

FIELD OF THE INVENTION

The present invention relates to therapeutic compositions and methods for the treatment or diagnosis of diseases or conditions related to NF-κB levels, such as restenosis, rheumatoid arthritis, asthma, inflammatory or autoimmune disorders and transplant rejection.

BACKGROUND OF THE INVENTION

The following is a brief description of the physiological role of NF-κB. The discussion is not meant to be complete and is provided only for understanding of the invention that follows. This summary is not an admission that any of the work described below is prior art to the claimed invention.

The nuclear DNA-binding activity, NF-κB, was first identified as a factor that binds and activates the immunoglobulin K light chain enhancer in B cells. NF-κB now is known to activate transcription of a variety of other cellular genes (e.g., cytokines, adhesion proteins, oncogenes and viral proteins) in response to a variety of stimuli (e.g., phorbol esters, mitogens, cytokines and oxidative stress). In addition, molecular and biochemical characterization of NF-κB has shown that the activity is due to a homodimer or heterodimer of a family of DNA binding subunits. Each subunit bears a stretch of 300 amino acids that is homologous to the oncogene, v-rel. The activity first described as NF-κB is a heterodimer of p49 or p50 with p65. The p49 and p50 subunits of NF-κB (encoded by the nf-κB2 or nf-κB1 genes, respectively) are generated from the precursors NF-κB1 (p105) or NF-κB2 (p100). The p65 subunit of NF-κB (now termed Rel A) is encoded by the rel A locus.

The roles of each specific transcription-activating complex now are being elucidated in cells (N. D. Perkins, et al., 1992 Proc. Natl. Acad. Sci USA 89, 1529-1533). For instance, the heterodimer of NF-κB1 and Rel A (p50/p65) activates transcription of the promoter for the adhesion molecule, VCAM-1, while NF-κB2/RelA heterodimers (p49/p65) actually inhibit transcription (H. B. Shu, et al., Mol. Cell. Biol. 13, 6283-6289 (1993)). Conversely, heterodimers of NF-κB2/RelA (p49/p65) act with Tat-I to activate transcription of the HIV genome, while NF-κB1/RelA (p50/p65) heterodimers have little effect (J. Liu, N. D. Perkins, R. M. Schmid, G. J. Nabel, J. Virol. 1992 66, 3883-3887). Similarly, blocking rel A gene expression with antisense oligonucleotides specifically blocks embryonic stem cell adhesion; blocking NF-κB1 gene expression with antisense oligonucleotides had no effect on cellular adhesion (Narayanan et al., 1993 Mol. Cell. Biol. 13, 3802-3810). Thus, the promiscuous role initially assigned to NF-κB in transcriptional activation (M. J. Lenardo, D. Baltimore, 1989 Cell 58, 227-229) represents the sum of the activities of the rel family of DNA-binding proteins. This conclusion is supported by recent transgenic “knock-out” mice of individual members of the rel family. Such “knock-outs” show few developmental defects, suggesting that essential transcriptional activation functions can be performed by more than one member of the rel family.

A number of specific inhibitors of NF-κB function in cells exist, including treatment with phosphorothioate antisense oliogonucleotide, treatment with double-stranded NF-κB binding sites, and over expression of the natural inhibitor MAD-3 (an IκB family member). These agents have been used to show that NF-κB is required for induction of a number of molecules involved in inflammation, as described below.

NF-κB is required for phorbol ester-mediated induction of IL-6 (I. Kitajima, et al., Science 258, 1792-5 (1992)) and IL-8 (Kunsch and Rosen, 1993 Mol. Cell. Biol. 13, 6137-46).

NF-κB is required for induction of the adhesion molecules ICAM-1 (Eck, et al., 1993 Mol. Cell. Biol. 13, 6530-6536), VCAM-1 (Shu et al., supra), and E-selectin (Read, et al., 1994 J. Exp. Med. 179, 503-512) on endothelial cells.

NF-κB is involved in the induction of the integrin subunit, CD18, and other adhesive properties of leukocytes (Eck et al., 1993 supra).

The above studies suggest that NF-κB is integrally involved in the induction of cytokines and adhesion molecules by inflammatory mediators. Two recent papers point to another connection between NF-κB and inflammation: glucocorticoids may exert their anti-inflammatory effects by inhibiting NF-κB. The glucocorticoid receptor and p65 both act at NF-κB binding sites in the ICAM-1 promoter (van de Stolpe, et al., 1994 J. Biol. Chem. 269, 6185-6192). Glucocorticoid receptor inhibits NF-κB-mediated induction of IL-6 (Ray and Prefontaine, 1994 Proc. Natl Acad. Sci USA 91, 752-756). Conversely, overexpression of p65 inhibits glucocorticoid induction of the mouse mammary tumor virus promoter. Finally, protein cross-linking and co-immunoprecipitation experiments demonstrated direct physical interaction between p65 and the glucocorticoid receptor (Id.).

SUMMARY OF THE INVENTION

This invention relates to ribozymes, or enzymatic RNA molecules, directed to cleave mRNA species encoding Rel A protein (p65). In particular, applicant describes the selection and function of ribozymes capable of cleaving this RNA and their use to reduce activity of NF-κB in various tissues to treat the diseases discussed herein. Such ribozymes are also useful for diagnostic applications.

Ribozymes that cleave rel A mRNA represent a novel therapeutic approach to inflammatory or autoimmune disorders. Antisense DNA molecules have been described that block NF-κB activity. See Narayanan et al., supra. However, ribozymes may show greater perdurance or lower effective doses than antisense molecules due to their catalytic properties and their inherent secondary and tertiary structures. Such ribozymes, with their catalytic activity and increased site specificity (as described below), represent more potent and safe therapeutic molecules than antisense oligonucleotides.

Applicant indicates that these ribozymes are able to inhibit the activity of NF-κB 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 rel A encoding mRNAs may be readily designed and are within the invention.

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.

The enzymatic nature of a ribozyme is advantageous over other technologies, such as antisense technology (where a nucleic acid molecule simply binds to a nucleic acid target to block its translation) since the concentration of ribozyme necessary to affect a therapeutic treatment is lower than that of an antisense oligonucleotide. 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. Similar mismatches in antisense molecules do not prevent their action (Woolf, T. M., et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 7305-7309). Thus, the specificity of action of a ribozyme is greater than that of an antisense oligonucleotide binding the same RNA site.

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., “RNA Catalyst for Cleaving Specific RNA Sequences,” filed Sep. 20, 1989, which is a continuation-in-part of U.S. Ser. No. 07/247,100 filed Sep. 20, 1988, Hampel and Tritz, 1989, Biochemistry, 28, 4929, and Hampel et al., 1990, Nucleic Acids Res.earch, 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.

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 Rel A encoding mRNA 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 vectors that are delivered to specific cells.

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, K. J., et al., 1991, Proc. Natl. Acad. Sci. USA, 88, 10591-5; Kashani-Sabet, M., et al., 1992, Antisense Res. Dev., 2, 3-15; Dropulic, B., et al., 1992, J. Virol, 66, 1432-41; Weerasinghe, M., et al., 1991, J. Virol, 65, 5531-4; Ojwang, J. O., et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen, C. J., et al., 1992, Nucleic Acids Res., 20, 4581-9; Sarver, H., 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 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, J., et al., 1992, Nucleic Acids Symp. Ser., 27, 15-6; Taira, K., et al., 1991, Nucleic Acids Res., 19, 5125-30; Ventura, M., et al., 1993, Nucleic Acids Res., 21, 3249-55).

Inflammatory mediators such as lipopolysaccharide (LPS), interleukin-1 (IL-1) or tumor necrosis factor-a (TNF-α) act on cells by inducing transcription of a number of secondary mediators, including other cytokines and adhesion molecules. In many cases, this gene activation is known to be mediated by the transcriptional regulator, NF-κB. One subunit of NF-κB, the relA gene product (termed RelA or p65) is implicated specifically in the induction of inflammatory responses. Ribozyme therapy, due to its exquisite specificity, is particularly well-suited to target intracellular factors that contribute to disease pathology. Thus, ribozymes that cleave mRNA encoded by rel A may represent novel therapeutics for the treatment of inflammatory and autoimmune disorders.

Thus, in a first aspect, the invention features ribozymes that inhibit RelA production. These chemically or enzymatically synthesized RNA molecules contain substrate binding domains that bind to accessible regions of their target mRNAs. The RNA molecules also contain domains that catalyze the cleavage of RNA. The RNA molecules are preferably ribozymes of the hammerhead or hairpin motif. Upon binding, the ribozymes cleave the target RelA encoding mRNAs, preventing translation and p65 protein accumulation. In the absence of the expression of the target gene, a therapeutic effect may be observed.

By “inhibit” is meant that the activity or level of RelA encoding mRNA is reduced below that observed in the absense of the ribozyme, and preferably is below that level observed in the presence of an inactive RNA molecule able to bind to the same site on the mRNA, but unable to cleave that RNA.

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 level of NF-κB activity in a cell or tissue. By “related” is meant that the inhibition of relA mRNA and thus reduction in the level of NF-κB activity will relieve to some extent the symptoms of the disease or condition.

Ribozymes are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells. The RNA or RNA complexes can be locally administered to relevant tissues ex vivo, or in vivo through injection or the use of a catheter, 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, III, VI-VII. Examples of such ribozymes are shown in Tables IV-VII. 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.

In another aspect of the invention, ribozymes that cleave target molecules and inhibit NF-κB activity are expressed from transcription units inserted into DNA, RNA, or viral vectors. Preferably, the recombinant vectors capable of expressing the ribozymes are locally delivered as described above, and transiently persist in target cells. Once expressed, the ribozymes cleave the target mRNA. The recombinant vectors are preferably DNA plasmids or adenovirus vectors. However, other mammalian cell vectors that direct the expression of RNA may be used for this purpose.

Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The drawings will first briefly be described.

DRAWINGS

FIG. 1 is a diagrammatic representation of the hammerhead ribozyme domain known in the art. [0027]
FIG. 2[0028] a is a diagrammatic representation of the hammerhead ribozyme domain known in the art;
FIG. 2[0029] b is a diagrammatic representation of the hammerhead ribozyme as divided by Uhlenbeck (1987, Nature, 327, 596-600) into a substrate and enzyme portion;
FIG. 2[0030] c is a similar diagram showing the hammerhead divided by Haseloff and Gerlach (1988, Nature, 334, 585-591) into two portions; and
FIG. 2[0031] d is a similar diagram showing the hammerhead divided by Jeffries and Symons (1989, Nucl. Acids. Res., 17, 1371-1371) into two portions.
FIG. 3 is a representation of the general structure of the hairpin ribozyme domain known in the art. [0032]
FIG. 4 is a representation of the general structure of the hepatitis delta virus ribozyme domain known in the art. [0033]
FIG. 5 is a representation of the general structure of the VS RNA ribozyme domain known in the art. [0034]
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.[0035]
Ribozymes [0036]
Ribozymes of this invention block to some extent NF-κB expression and can be used to treat disease or diagnose such disease. Ribozymes will be delivered to cells in culture and to cells or tissues in animal models of restenosis, transplant rejection and rheumatoid arthritis. Ribozyme cleavage of relA mRNA in these systems may prevent inflammatory cell function and alleviate disease symptoms. [0037]
Target Sites [0038]
Targets for useful ribozymes can be determined as disclosed in Draper et al supra, Sullivan et al., supra, as well as by 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. Such ribozymes can also be optimized and delivered as described therein. While specific examples to mouse and human RNA are provided, those in the art will recognize that the equivalent human RNA targets described can be used as described below. Thus, the same target may be used, but binding arms suitable for targeting human RNA sequences are present in the ribozyme. Such targets may also be selected as described below. [0039]
The sequence of human and mouse relA mRNA can be screened for accessible sites using a computer folding algorithm. Potential hammerhead or hairpin ribozyme cleavage sites were identified. These sites are shown in Tables II, III, and VI-VII. (All sequences are 5′ to 3′ in the tables.) While mouse and human sequences can be screened and ribozymes thereafter designed, the human targetted sequences are of most utility. However, as discussed in Stinchcomb et al. supra, mouse targetted ribozmes are 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. (In Table II, lower case letters indicate positions that are not conserved between the Human and the Mouse relA sequences.) [0040]
Hammerhead ribozymes are designed that could bind and are individually analyzed by computer folding (Jaeger, J. A., et al., 1989, [0041] Proc. Natl. Acad. Sci. USA, 86, 7706-7710) to assess whether, the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core are eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.
Referring to FIG. 6, mRNA is screened for accessible cleavage sites by the method described generally in Draper et al., WO/US93/04020 hereby incorporated by reference herein. Briefly, DNA oligonucleotides representing potential hammerhead ribozyme cleavage sites are synthesized. A polymerase chain reaction is used to generate a substrate for T7 RNA polymerase transcription from human or murine rel A cDNA clones. Labeled RNA transcripts are synthesized in vitro from the two templates. The oligonucleotides and the labeled transcripts are annealed, RNAseH is added and the mixtures are 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 phosphor imaging system. From these data, hammerhead ribozyme sites are chosen as the most accessible. [0042]
Ribozymes of the hammerhead 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, N.; Ogilvie, K. K.; Jiang, M. -Y.; Cedergren, R. J. 1987, [0043] J. Am. Chem. Soc., 109, 7845-7854 and in Scaringe, S. A.; Franklyn, C.; Usman, N., 1990, Nucleic Acids Res., 18, 5433-5441 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 G₅and a U for A₁₄(numbering from (Hertel, K. J., et al., 1992, Nucleic Acids Res., 20, 3252)). Hairpin ribozymes are synthesized in two parts and annealed to reconstruct the active ribozyme (Chowrira, B. M. and Burke, J. M., 1992, Nucleic Acids Res., 20, 2835-2840). All ribozymes are modified to enhance stability by modification of five ribonucleotides at both the 5′ and 3′ ends with 2′-O-methyl groups. 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.
The sequences of the chemically synthesized ribozymes useful in this study are shown in Tables IV-VII. 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 and may be formed of ribonucleotides or other nucleotides or non-nucleotides. Such ribozymes are equivalent to the ribozymes described specifically in the Tables. [0044]
Optimizing Ribozyme Activity [0045]
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. 2[0046] c), 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., Nature 1990, 344:565; Pieken et al., Science 1991, 253:314; Usman and Cedergren, Trends in Biochem. Sci. 1992, 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, B. European Patent Application 92110298.4 which describe various chemical modifications that can be made to the sugar moieties of enzymatic RNA molecules. All these publications are hereby incorporated by reference herein.), modifications which enhance their efficacy in cells, and removal of stem II bases to shorten RNA synthesis times and reduce chemical requirements.
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, intrvascular, 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. [0047]
Another means of accumulating high concentrations of a ribozyme(s) within cells is to incorporate the ribozyme-encoding sequences into a DNA 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, O. and Moss, B., 1990, [0048] Proc. Natl. Acad. Sci. USA, 87, 6743-7; Gao, X. and Huang, L., 1993, Nucleic Acids Res., 21, 2867-72; Lieber, A., et al., 1993, Methods Enzymol., 217, 47-66; Zhou, Y., 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, M., et al., 1992, Antisense Res. Dev., 2, 3-15; Ojwang, J. O., et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen, C. J., et al., 1992, Nucleic Acids Res., 20, 4581-9; Yu, M., et al., 1993, Proc. Natl. Acad. Sci. USA, 96, 6340-4; L'Huillier, P. J., et al., 1992, Embo J., 11, 4411-8; Lisziewicz, J., 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 vectors), or viral RNA vectors (such as retroviral vectors).
In a preferred embodiment of the invention, a transcription unit expressing a ribozyme that cleaves relA RNA is inserted into a plasmid DNA vector or an adenovirus DNA viral vector. Both vectors have been used to transfer genes to the intact vasculature or to joints of live animals (Willard, J. E., et al., 1992, [0049] Circulation, 86, 1-473.; Nabel, E. G., et al., 1990, Science, 249, 1285-1288.) and both vectors lead to transient gene expression. The adenovirus vector is delivered as recombinant adenoviral particles. DNA may be delivered alone or complexed with vehicles (as described for RNA above). The DNA, DNA/vehicle complexes, or the recombinant adenovirus particles are locally administered to the site of treatment, e.g., through the use of an injection catheter, stent or infusion pump or are directly added to cells or tissues ex vivo.

EXAMPLE 1

NF-κB Hammerhead Ribozymes

By engineering ribozyme motifs we have designed several ribozymes directed against relA mRNA sequences. These ribozymes are synthesized with modifications that improve their nuclease resistance. The ability of ribozymes to cleave relA target sequences in vitro is evaluated. [0050]
The ribozymes will be tested for function in vivo by analyzing cytokine-induced VCAM-1, ICAM-1, IL-6 and IL-8 expression levels. Ribozymes will be delivered to cells by incorporation into liposomes, by complexing with cationic lipids, by microinjection, or by expression from DNA vectors. Cytokine-induced VCAM-1, ICAM-1, IL-6 and IL-8 expression will be monitored by ELISA, by indirect immunofluoresence, and/or by FACS analysis. Rel A mRNA levels will be assessed by Northern analysis, RNAse protection or primer extension analysis or quantitative RT-PCR. Activity of NF-κB will be monitored by gel-retardation assays. Ribozymes that block the induction of NF-κB activity and/or rel A mRNA by more than 50% will be identified. [0051]
RNA ribozymes and/or genes encoding them will be locally delivered to transplant tissue ex vivo in animal models. Expression of the ribozyme will be monitored by its ability to block ex vivo induction of VCAM-1, ICAM-1, IL-6 and IL-8 mRNA and protein. The effect of the anti-rel A ribozymes on graft rejection will then be assessed. Similarly, ribozymes will be introduced into joints of mice with collagen-induced arthritis or rabbits with Streptococcal cell wall-induced arthritis. Liposome delivery, cationic lipid delivery, or adeno-associated virus vector delivery can be used. One dose (or a few infrequent doses) of a stable anti-relA ribozyme or a gene construct that constitutively expresses the ribozyme may abrogate inflammatory and immune responses in these diseases. [0052]
Uses [0053]
A therapeutic agent that inhibits cytokine gene expression, inhibits adhesion molecule expression, and mimics the anti-inflammatory effects of glucocorticoids (without inducing steroid-responsive genes) is ideal for the treatment of inflammatory and autoimmune disorders. Disease targets for such a drug are numerous. Target indications and the delivery options each entails are summarized below. In all cases, because of the potential immunosuppressive properties of a ribozyme that cleaves rel A mRNA, uses are limited to local delivery, acute indications, or ex vivo treatment. [0054]
*Rheumatoid Arthritis (RA). [0055]
Due to the chronic nature of RA, a gene therapy approach is logical. Delivery of a ribozyme to inflamed joints is mediated by adenovirus, retrovirus, or adeno-associated virus vectors. For instance, the appropriate adenovirus vector can be administered by direct injection into the synovium: high efficiency of gene transfer and expression for several months would be expected (B. J. Roessler, E. D. Allen, J. M. Wilson, J. W. Hartman, B. L. Davidson, J. Clin. Invest. 92, 1085-1092 (1993)). It is unlikely that the course of the disease could be reversed by the transient, local administration of an anti-inflammatory agent. Multiple administrations may be necessary. Retrovirus and adeno-associated virus vectors would lead to permanent gene transfer and expression in the joint. However, permanent expression of a potent anti-inflammatory agent may lead to local immune deficiency. [0056]
Restenosis. [0057]
Expression of NF-κB in the vessel wall of pigs causes a narrowing of the luminal space due to excessive deposition of extracellular matrix components. This phenotype is similar to matrix deposition that occurs subsequent to coronary angioplasty. In addition, NF-κB is required for the expression of the oncogene c-myb (F. A. La Rosa, J. W. Pierce, G. E. Soneneshein, Mol. Cell. Biol. 14, 1039-44 (1994)). Thus NF-κB induces smooth muscle proliferation and the expression of excess matrix components: both processes are thought to contribute to reocclusion of vessels after coronary angioplasty. [0058]
*Transplantation. [0059]
NF-κB is required for the induction of adhesion molecules (Eck et al., supra, K. O'Brien, et al., J. Clin. Invest. 92, 945-951 (1993)) that function in immune recognition and inflammatory responses. At least two potential modes of treatment are possible. In the first, transplanted organs are treated ex vivo with ribozymes or ribozyme expression vectors. Transient inhibition of NF-κB in the transplanted endothelium may be sufficient to prevent transplant-associated vasculitis and may significantly modulate graft rejection. In the second, donor B cells are treated ex vivo with ribozymes or ribozyme expression vectors. Recipients would receive the treatment prior to transplant. Treatment of a recipient with B cells that do not express T cell co-stimulatory molecules (such as ICAM-1, VCAM-1, and/or B7 an B7-2) can induce antigen-specific anergy. Tolerance to the donor's histocompatibility antigens could result; potentially, any donor could be used for any transplantation procedure. [0060]
*Asthma. [0061]
Granulocyte macrophage colony stimulating factor (GM-CSF) is thought to play a major role in recruitment of eosinophils and other inflammatory cells during the late phase reaction to asthmatic trauma. Again, blocking the local induction of GM-CSF and other inflammatory mediators is likely to reduce the persistent inflammation observed in chronic asthmatics. Aerosol delivery of ribozymes or adenovirus ribozyme expression vectors is a feasible treatment. [0062]
Gene Therapy. [0063]
Immune responses limit the efficacy of many gene transfer techniques. Cells transfected with retrovirus vectors have short lifetimes in immune competent individuals. The length of expression of adenovirus vectors in terminally differentiated cells is longer in neonatal or immune-compromised animals. Insertion of a small ribozyme expression cassette that modulates inflammatory and immune responses into existing adenovirus or retrovirus constructs will greatly enhance their potential. [0064]
Thus, ribozymes of the present invention that cleave rel A mRNA and thereby NF-κB activity have many potential therapeutic uses, and there are reasonable modes of delivering the ribozymes in a number of the possible indications. Development of an effective ribozyme that inhibits NF-κB function is described above; available cellular and activity assays are number, reproducible, and accurate. Animal models for NF-κB function (Kitajima, et al., supra) and for each of the suggested disease targets exist and can be used to optimize activity. [0065]
Diagnostic Uses [0066]
Ribozymes of this invention may be used as diagnostic tools to examine genetic drift and mutations within diseased cells. 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 mRNA associated with an NF-κB related condition. Such RNA is detected by determining the presence of a cleavage product after treatment with a ribozyme using standard methodology. [0067]
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., NF-κB) 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. [0068]

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

(FIGS. 1 and 2 show examples of various manifestations as used

in the art).

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).

TABLE II


Mouse rel A HH Target sequence

nt.	HH Target	Seq. ID	nt.	HH Target	Seq.
Pos.	Sequence	No.	Pos.	Sequence	ID No.

19	AAUGGCU a caCaGgA	7	467	cCAGGCU c cuguUCg	108

22	aGCUCcU a cGUgGUG	8	469	AaGCcAU u AGcCAGC	109

26	CcUCcaU u GcGgACa	9	473	UuUgAGU C AGauCAg	110

93	GAuCUGU U uCCCCUC	10	481	AGCGaAU C CAGACCA	111

94	AuCUGUU u CCCCUCA	11	501	AACCCCU U uCAcGUU	112

100	UuCCCCU C AUCUUuC	12	502	ACCCCUU u CAcGUUC	113

103	CCCUCAU C UuuCCcu	13	508	UuCAcGU U CCUAUAG	114

105	CUCAUCU U uCCcuCA	14	509	uCAcGUU C CUAUAGA	115

106	UCAUCUU u CccuCAG	15	512	cGUUCCU A UAGAgGA	116

129	CAGGCuU C UGGgCCu	16	514	UUCCUAU A GAgGAGC	117

138	GGgCCuU A UGUGGAG	17	534	GGGGACU A uGACuUG	118

148	UGGAGAU C AucGAaC	18	556	UGCGcCU C UGCUUCC	119

151	AGAUCAU c GaaCAGC	19	561	CUCUGCU U CCAGGUG	120

180	AUGCGaU U CCGCUAu	20	562	UCUGCUU C CAGGUGA	121

181	UGCGaUU C CGCUAuA	21	585	aAgCCAU u AGcCAGc	122

186	UUCCGCU A uAAaUGC	22	598	GGCCCCU C CuCCUGa	123

204	GGGCGCU C aGCGGGC	23	613	CcCCUGU C CUcuCaC	124

217	GCAGuAU U CcuGGCG	24	616	CUGUCCU c uCaCAUC	125

239	CACAGAU A CCACCAA	25	617	gucCCUU C CUCAgCC	126

262	CCACCAU C AAGAUCA	26	620	CCUUCCU C AgCCaug	127

268	UCAAGAU C AAUGGCU	27	623	UCCUgcU u CCAUCUc	128

276	AAUGGCU A CACAGGA	28	628	AUCCGAU U UUUGAUA	129

301	UuCGaAU C UCCCUGG	29	630	CCgAUuU U UGAuAAc	130

303	CGaAUCU C CCUGGUC	30	631	CgAUuUU U GAuAAcC	131

310	CCCUGGU C ACCAAGG	31	638	UGgCcAU u GUGuuCC	132

323	GGcCCCU C CUCcuga	32	661	CCGAGCU C AAGAUCU	133

326	uCCaCCU C ACCGGCC	33	667	UCAAGAU C UGCCGAG	134

335	CCGGCCU C AuCCaCA	34	687	CGgAACU C UGGgAGC	135

349	AuGAaCU U GugGGgA	35	700	GCUGCCU C GGUGGGG	136

352	AGaUcaU c GaAcAGc	36	715	AUGAGAU C UUCuUgC	137

375	GAUGGCU a CUAUGAG	37	717	GAGAUCU U CuUgCUG	138

376	AUGGucU C UccGgaG	38	718	AGAUCUU C uUgCUGU	139

378	GGCUaCU A UGAGGCU	39	721	UucUCCU c CauUGcG	140

391	CUGAcCU C UGCCCaG	40	751	AaGACAU U GAGGUGU	141

409	GCaGuAU C CauAGcU	41	759	GAGGUGU A UUUCACG	142

416	CCgCAGU a UCCAuAg	42	761	GGUGUAU U UCACGGG	143

417	CAuAGcU U CCAGAAC	43	762	GUGUAUU U CACGGGA	144

418	AuAGcUU C CAGAACC	44	763	UGUAUUU C ACGGGAC	145

433	UGGGgAU C CAGUGUG	45	792	CGAGGCU C CUUUUCu	146

795	GGCUCCU U UUCuCAA	46	1167	GAUGAGU U UuCCcCC	147

796	GCUCCUU U UcuCAAG	47	1168	AUGAGUU U uCCcCCA	148

797	CUCCUUU U CuCAAGC	48	1169	UGAGUUU u CCcCCAU	149

798	UCCUUUU C uCAAGCU	49	1182	AUGcUGU U aCCaUCa	150

829	UGGCCAU U GUGUUCC	50	1183	UGcUGUU a CCaUCaG	151

834	AUUGUGU U CCGGACu	51	1184	GGccccU C CUcCUGa	152

835	UUGUGUU C CGGACuC	52	1187	GUccCuU c CUcAGCc	153

845	GACuCCU C CgUACGC	53	1188	UUaCCaU C aGGGCAG	154

849	CCUCCgU A CGCcGAC	54	1198	GGgAGuU u AGuCuGa	155

872	cCAGGCU C CUGUuCG	55	1209	CAGcCCU a caCCUUc	156

883	UuCGaGU C UCCAUGC	56	1215	cuGGCCU U aGCaCCG	157

885	CGaGUCU C CAUGCAG	57	1229	GGuCCCU u CCucAGc	158

905	GCGGCCU U CuGAuCG	58	1237	CCCAgcU C CUGCCCC	159

906	CGGCCUU C uGAuCGc	59	1250	CCAGcCU C CAGgCUC	160

919	GcGAGCU C AGUGAGC	60	1268	CCCaGCU C CuGCCcc	161

936	AUGGAgU U CCAGUAC	61	1279	CCAUGGU c cCuuCcu	162

937	UGGAgUU C CAGUACu	62	1281	gUGGgcU C AGCUgcG	163

942	UUCCAGU A CuUGCCA	63	1286	AUgAGuU u UccCCCA	164

953	GCCucAU c CacAuGA	64	1309	CuCCUGU u CgAGUCu	165

962	AGAuGAU C GcCACCG	65	1315	cCCCAGU u CUAaCCC	166

965	CagUacU u gCCaGAc	66	1318	CAGUuCA A aCCCCgG	167

973	ACCGGAU U GaaGAGA	67	1331	gGGuCCU C CcCAGuC	168

986	GAgACcU u cAAGagu	68	1334	CuuUuCU C AaGCUGa	169

996	AGGACcU A UGAGACC	69	1389	ACGCUGU C gGAaGCC	170

1005	GAGACCU U CAAGAGu	70	1413	CUGCAGU U UGAUGcU	171

1006	AGACCUU C AAGAGuA	71	1414	UGCAGUU U GAUGcUG	172

1015	AGAGuAU C AUGAAGA	72	1437	GGGGCCU U GCUUGGC	173

1028	GAAGAGU C CUUUCAa	73	1441	CCUUGCU U GGCAACA	174

1031	GAGUCCU U UCAauGG	74	1467	GgaGUGU U CACAGAC	175

1032	AGUCCUU U CaauGGA	75	1468	gaGUGUU C ACAGACC	176

1033	GUCCUUU C AauGGAC	76	1482	CUGGCAU C uGUgGAC	177

1058	CCGGCCU C CaaCcCG	77	1486	CuUCgGU a GggAACU	178

1064	UaCACCU u GaucCAa	78	1494	GACAACU C aGAGUUU	179

1072	GgCGuAU U GCUGUGC	79	1500	UCaGAGU U UCAGCAG	180

1082	UGUGCCU a CCCGaAa	80	1501	CaGAGUU U CAGCAGC	181

1083	aaGCCUU C CCGaAGu	81	1502	aGAGUUU C AGCAGCU	182

1092	CGaAaCU C AaCUUCU	82	1525	gGuGCAU c CCUGUGu	183

1097	CUCAaCU U CUGUCCC	83	1566	AUGGAGU A CCCUGAa	184

1098	UCAaCUU C UGUCCCC	84	1577	UGAaGCU A UAACUCG	185

1102	CUUCUGU C CCCAAGC	85	1579	AaGCUAU A ACUCGCC	186

1125	CAGCCCU A caCCUUc	86	1583	UAUAACU C GCCUgGU	187

1127	GCCaUAU a gCcUUAC	87	1588	CUCuCCU A GaGAggG	188

1131	cAUCCCU c agCacCA	88	1622	CCCAGCU C CUGCcCC	189

1132	AcaCCUU c cCagCAU	89	1628	UCCUGCU u CggUaGG	190

1133	UCCaUcU c CagCuUC	90	1648	CGGGGCU u CCCAAUG	191

1137	UUUACuU u AgCgCgc	91	1660	cUGaCCU C ugccCAG	192

1140	cCagCAU C CCUcAGC	92	1663	cuCUgCU U cCAGGuG	193

1153	GCACCAU C AACUuUG	93	1664	uCUgCUU c CAGGuGA	194

1158	AUCAACU u UGAUGAG	94	1665	CUCgcUU u cGGAGgU	195

1680	GAAGACU U CUCCUCC	95

1681	AAGACUU C UCCUCCA	96

1683	GACUUCU C CUCCAUU	97

1686	UUCUCCU C CAUUGCG	98

1690	CCUCCAU U GCGGACA	99

1704	AUGGACU U CUCuGCu	100

1705	UGGACUU C UCuGCuC	101

1707	GACUUCU C uGCuCUu	102

1721	uuUGAGU C AGAUCAG	103

1726	GUCAGAU C AGCUCCU	104

1731	AUCAGCU C CUAAGGu	105

1734	AGCUCCU A AGGuGcU	106

1754	CaGugCU C CCaAGAG	107

TABLE III


Human rel A HH Target Sequences

nt.	HH Target	Seq. ID	nt.	HH Target	Seq. ID
Pos.	Sequence	No.	Pos.	Sequence	No.

19	AAUGGCU C GUCUGUA	196	467	GCAGGCU A UCAGUCA	297

22	GGCUCGU C UGUAGUG	197	469	AGGCUAU C AGUCAGC	298

26	CGUCUGU A GUGCACG	198	473	UAUCAGU C AGCGCAU	299

93	GAACUGU U CCCCCUC	199	481	AGCGCAU C CAGACCA	300

94	AACUGUU C CCCCUCA	200	501	AACCCCU U CCAAGUU	301

100	UCCCCCU C AUCUUCC	201	502	ACCCCUU C CAAGUUC	302

103	CCCUCAU C UUCCCGG	202	508	UCCAAGU U CCUAUAG	303

105	CUCAUCU U CCCGGCA	203	509	CCAAGUU C CUAUAGA	304

106	UCAUCUU C CCGGCAG	204	512	AGUUCCU A UAGAAGA	305

129	CAGGCCU C UGGCCCC	205	514	UUCCUAU A GAAGAGC	306

138	GGCCCCU A UGUGGAG	206	534	GGGGACU A CGACCUG	307

148	UGGAGAU C AUUGAGC	207	556	UGCGGCU C UGCUUCC	308

151	AGAUCAU U GAGCAGC	208	561	CUCUGCU U CCAGGUG	309

180	AUGCGCU U CCGCUAC	209	562	UCUGCUU C CAGGUGA	310

181	UGCGCUU C CGCUACA	210	585	GACCCAU C AGGCAGG	311

186	UUCCGCU A CAAGUGC	211	598	GGCCCCU C CGCCUGC	312

204	GGGCGCU C CGCGGGC	212	613	CGCCUGU C CUUCCUC	313

217	GCAGCAU C CCAGGCG	213	616	CUGUCCU U CCUCAUC	314

239	CACAGAU A CCACCAA	214	617	UGUCCUU C CUCAUCC	315

262	CCACCAU C AAGAUCA	215	620	CCUUCCU C AUCCCAU	316

268	UCAAGAU C AAUGGCU	216	623	UCCUCAU C CCAUCUU	317

276	AAUGGCU A CACAGGA	217	628	AUCCCAU C UUUGACA	318

301	UGCGCAU C UCCCUGG	218	630	CCCAUCU U UGACAAU	319

303	CGCAUCU C CCUGGUC	219	631	CCAUCUU U GACAAUC	320

310	CCCUGGU C ACCAAGG	220	638	UGACAAU C GUGCCCC	321

323	GGACCCU C CUCACCG	221	661	CCGAGCU C AAGAUCU	322

326	CCCUCCU C ACCGGCC	222	667	UCAAGAU C UGCCGAG	323

335	CCGGCCU C ACCCCCA	223	687	CGAAACU C UGGCAGC	324

349	ACGAGCU U GUAGGAA	224	700	GCUGCCU C GGUGGGG	325

352	AGCUUGU A GGAAAGG	225	715	AUGAGAU C UUCCUAC	326

375	GAUGGCU U CUAUGAG	226	717	GAGAUCU U CCUACUG	327

376	AUGGCUU C UAUGAGG	227	718	AGAUCUU C CUACUGU	328

378	GGCUUCU A UGAGGCU	228	721	UCUUCCU A CUGUGUG	329

391	CUGAGCU C UGCCCGG	229	751	AGGACAU U GAGGUGU	330

409	GCUGCAU C CACAGUU	230	759	GAGGUGU A UUUCACG	331

416	CCACAGU U UCCAGAA	231	761	GGUGUAU U UCACGGG	332

417	CACAGUU U CCAGAAC	232	762	GUGUAUU U CACGGGA	333

418	ACAGUUU C CAGAACC	233	763	UGUAUUU C ACGGGAC	334

433	UGGGAAU C CAGUGUG	234	792	CGAGGCU C CUUUUCG	335

795	GGCUCCU U UUCGCAA	235	1167	GAUGAGU U UCCCACC	336

796	GCUCCUU U UCGCAAG	236	1168	AUGAGUU U CCCACCA	337

797	CUCCUUU U CGCAAGC	237	1169	UGAGUUU C CCACCAU	338

798	UCCUUUU C GCAAGCU	238	1182	AUGGUGU U UCCUUCU	339

829	UGGCCAU U GUGUUCC	239	1183	UGGUGUU U CCUUCUG	340

834	AUUGUGU U CCGGACC	240	1184	GGUGUUU C CUUCUGG	341

835	UUGUGUU C CGGACCC	241	1187	GUUUCCU U CUGGGCA	342

845	GACCCCU C CCUACGC	242	1188	UUUCCUU C UGGGCAG	343

849	CCUCCCU A CGCAGAC	243	1198	GGCAGAU C AGCCAGG	344

872	GCAGGCU C CUGUGCG	244	1209	CAGGCCU C GGCCUUG	345

883	UGCGUGU C UCCAUGC	245	1215	UCGGCCU U GGCCCCG	346

885	CGUGUCU C CAUGCAG	246	1229	GGCCCCU C CCCAAGU	347

905	GCGGCCU U CCGACCG	247	1237	CCCAAGU C CUGCCCC	348

906	CGGCCUU C CGACCGG	248	1250	CCAGGCU C CAGCCCC	349

919	GGGAGCU C AGUGAGC	249	1268	CCCUGCU C CAGCCAU	350

936	AUGGAAU U CCAGUAC	250	1279	CCAUGGU A UCAGGUC	351

937	UGGAAUU C CAGUACC	251	1281	AUGGUAU C AGCUCUG	352

942	UUCCAGU A CCUGCCA	252	1286	AUCAGCU C UGGCCCA	353

953	GCCAGAU A CAGACGA	253	1309	CCCCUGU C CCAGUCC	354

962	AGACGAU C GUCACCG	254	1315	UCCCAGU C CUAGCCC	355

965	CGAUCGU C ACCGGAU	255	1318	CAGUCCU A GCCCCAG	356

973	ACCGGAU U GAGGAGA	256	1331	AGGCCCU C CUCAGGC	357

986	GAAACGU A AAAGGAC	257	1334	CCCUCCU C AGGCUGU	358

996	AGGACAU A UGAGACC	258	1389	ACGCUGU C AGAGGCC	359

1005	GAGACCU U CAAGAGC	259	1413	CUGCAGU U UGAUGAU	360

1006	AGACCUU C AAGAGCA	260	1414	UGCAGUU U GAUGAUG	361

1015	AGAGCAU C AUGAAGA	261	1437	GGGGCCU U GCUUGGC	362

1028	GAAGAGU C CUUUCAG	262	1441	CCUUGCU U GGCAACA	363

1031	GAGUCCU U UCAGCGG	263	1467	GCUGUGU U CACAGAC	364

1032	AGUCCUU U CAGCGGA	264	1468	CUGUGUU C ACAGACC	365

1033	GUCCUUU C AGCGGAC	265	1482	CUGGCAU C CGUCGAC	366

1058	CCGGCCU C CACCUCG	266	1486	CAUCCGU C GACAACU	367

1064	UCCACCU C GACGCAU	267	1494	GACAACU C CGAGUUU	368

1072	GACGCAU U GCUGUGC	268	1500	UCCGAGU U UCAGCAG	369

1082	UGUGCCU U CCCGCAG	269	1501	CCGAGUU U CAGCAGC	370

1083	GUGCCUU C CCGCAGC	270	1502	CGAGUUU C AGCAGCU	371

1092	CGCAGCU C AGCUUCU	271	1525	AGGGCAU A CCUGUGG	372

1097	CUCAGCU U CUGUCCC	272	1566	AUGGAGU A CCCUGAG	373

1098	UCAGCUU C UGUCCCC	273	1577	UGAGGCU A UAACUCG	374

1102	CUUCUGU C CCCAAGC	274	1579	AGGCUAU A ACUCGCC	375

1125	CAGCCCU A UCCCUUU	275	1583	UAUAACU C GCCUAGU	376

1127	GCCCUAU C CCUUUAC	276	1588	CUCGCCU A GUGACAG	377

1131	UAUCCCU U UACGUCA	277	1622	CCCAGCU C CUGCUCC	378

1132	AUCCCUU U ACGUCAU	278	1628	UCCUGCU C CACUGGG	379

1133	UCCCUUU A CGUCAUC	279	1648	CGGGGCU C CCCAAUG	380

1137	UUUACGU C AUCCCUG	280	1660	AUGGCCU C CUUUCAG	381

1140	ACGUCAU C CCUGAGC	281	1663	GCCUCCU U UCAGGAG	382

1153	GCACCAU C AACUAUG	282	1664	CCUCCUU U CAGGAGA	383

1158	AUCAACU A UGAUGAG	283	1665	CUCCUUU C AGGAGAU	384

1680	GAAGACU U CUCCUCC	284

1681	AAGACUU C UCCUCCA	285

1683	GACUUCU C CUCCAUU	286

1686	UUCUCCU C CAUUGCG	287

1690	CCUCCAU U GCGGACA	288

1704	AUGGACU U CUCAGCC	289

1705	UGGACUU C UCAGCCC	290

1707	GACUUCU C AGCCCUG	291

1721	GCUGAGU C AGAUCAG	292

1726	GUCAGAU C AGCUCCU	293

1731	AUCAGCU C CUAAGGG	294

1734	AGCUCCU A AGGGGGU	295

1754	CUGCCCU C CCCAGAG	296

TABLE IV


Mouse rel A HH Ribozyme Sequences

nt. Seq.	HH Ribozyme Sequence	Seq. ID No.

19	UCCUGUG CUGAUGAGGCCGAAAGGCCGAA AGCCAUU	385

22	CACCACG CUGAUGAGGCCGAAAGGCCGAA AGGAGCU	386

26	UGUCCGC CUGAUGAGGCCGAAAGGCCGAA AUGGAGG	387

93	GAGGGGA CUGAUGAGGCCGAAAGGCCGAA ACAGAUC	388

94	UGAGGGG CUGAUGAGGCCGAAAGGCCGAA AACAGAU	389

100	GAAAGAU CUGAUGAGGCCGAAAGGCCGAA AGGGGAA	390

103	AGGGAAA CUGAUGAGGCCGAAAGGCCGAA AUGAGGG	391

105	UGAGGGA CUGAUGAGGCCGAAAGGCCGAA AGAUGAG	392

106	CUGAGGG CUGAUGAGGCCGAAAGGCCGAA AAGAUGA	393

129	AGGCCCA CUGAUGAGGCCGAAAGGCCGAA AAGCCUG	394

138	CUCCACA CUGAUGAGGCCGAAAGGCCGAA AAGGCCC	395

148	GUUCGAU CUGAUGAGGCCGAAAGGCCGAA AUCUCCA	396

151	GCUGUUC CUGAUGAGGCCGAAAGGCCGAA AUGAUCU	397

180	AUAGCGG CUGAUGAGGCCGAAAGGCCGAA AUCGCAU	398

181	UAUAGCG CUGAUGAGGCCGAAAGGCCGAA AAUCGCA	399

186	GCAUUUA CUGAUGAGGCCGAAAGGCCGAA AGCGGAA	400

204	GCCCGCU CUGAUGAGGCCGAAAGGCCGAA AGCGCCC	401

217	CGCCAGG CUGAUGAGGCCGAAAGGCCGAA AUACUGC	402

239	UUGGUGG CUGAUGAGGCCGAAAGGCCGAA AUCUGUG	403

262	UGAUCUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGG	404

268	AGCCAUU CUGAUGAGGCCGAAAGGCCGAA AUCUUGA	405

276	UCCUGUG CUGAUGAGGCCGAAAGGCCGAA AGCCAUU	406

301	CCAGGGA CUGAUGAGGCCGAAAGGCCGAA AUUCGAA	407

303	GACCAGG CUGAUGAGGCCGAAAGGCCGAA AGAUUCG	408

310	CCUUGGU CUGAUGAGGCCGAAAGGCCGAA ACCAGGG	409

323	UCAGGAG CUGAUGAGGCCGAAAGGCCGAA AGGGGCC	410

326	GGCCGGU CUGAUGAGGCCGAAAGGCCGAA AGGUGGA	411

335	UGUGGAU CUGAUGAGGCCGAAAGGCCGAA AGGCCGG	412

349	UCCCCAC CUGAUGAGGCCGAAAGGCCGAA AGUUCAU	413

352	GCUGUUC CUGAUGAGGCCGAAAGGCCGAA AUGAUCU	414

375	CUCAUAG CUGAUGAGGCCGAAAGGCCGAA AGCCAUC	415

376	CUCCGGA CUGAUGAGGCCGAAAGGCCGAA AGACCAU	416

378	AGCCUCA CUGAUGAGGCCGAAAGGCCGAA AGUAGCC	417

391	CUGGGCA CUGAUGAGGCCGAAAGGCCGAA AGGUCAG	418

391	CUGGGCA CUGAUGAGGCCGAAAGGCCGAA AGGUCAG	428

409	AGCUAUG CUGAUGAGGCCGAAAGGCCGAA AUACUGC	419

416	CUAUGGA CUGAUGAGGCCGAAAGGCCGAA ACUGCGG	420

417	GUUCUGG CUGAUGAGGCCGAAAGGCCGAA AGCUAUG	421

418	GGUUCUG CUGAUGAGGCCGAAAGGCCGAA AAGCUAU	422

433	CACACUG CUGAUGAGGCCGAAAGGCCGAA AUCCCCA	423

467	CGAACAG CUGAUGAGGCCGAAAGGCCGAA AGCCUGG	424

469	GCUGGCU CUGAUGAGGCCGAAAGGCCGAA AUGGCUU	425

473	CUGAUCU CUGAUGAGGCCGAAAGGCCGAA ACUCAAA	426

481	UGGUCUG CUGAUGAGGCCGAAAGGCCGAA AUUCGCU	427

501	AACGUGA CUGAUGAGGCCGAAAGGCCGAA AGGGGUU	428

502	GAACGUG CUGAUGAGGCCGAAAGGCCGAA AAGGGGU	429

508	CUAUAGG CUGAUGAGGCCGAAAGGCCGAA ACGUGAA	430

509	UCUAUAG CUGAUGAGGCCGAAAGGCCGAA AACGUGA	431

512	UCCUCUA CUGAUGAGGCCGAAAGGCCGAA AGGAACG	432

514	GCUCCUC CUGAUGAGGCCGAAAGGCCGAA AUAGGAA	433

534	CAAGUCA CUGAUGAGGCCGAAAGGCCGAA AGUCCCC	434

556	GGAAGCA CUGAUGAGGCCGAAAGGCCGAA AGGCGCA	435

561	CACCUGG CUGAUGAGGCCGAAAGGCCGAA AGGAGAG	436

562	UCACCUG CUGAUGAGGCCGAAAGGCCGAA AAGCAGA	437

585	GCUGGCU CUGAUGAGGCCGAAAGGCCGAA AUGGCUU	438

598	UCAGGAG CUGAUGAGGCCGAAAGGCCGAA AGGGGCC	439

613	GUGAGAG CUGAUGAGGCCGAAAGGCCGAA ACAGGGG	440

616	GAUGUGA CUGAUGAGGCCGAAAGGCCGAA AGGACAG	441

617	GGCUGAG CUGAUGAGGCCGAAAGGCCGAA AAGGGAC	442

620	CAUGGCU CUGAUGAGGCCGAAAGGCCGAA AGGAAGG	443

623	GAGAUGG CUGAUGAGGCCGAAAGGCCGAA AGCAGGA	444

628	UAUCAAA CUGAUGAGGCCGAAAGGCCGAA AUCGGAU	445

630	GUUAUCA CUGAUGAGGCCGAAAGGCCGAA AAAUCGG	446

631	GGUUAUC CUGAUGAGGCCGAAAGGCCGAA AAAAUCG	447

638	GGAACAC CUGAUGAGGCCGAAAGGCCGAA AUGGCCA	448

661	AGAUCUU CUGAUGAGGCCGAAAGGCCGAA AGCUCGG	449

667	CUCGGCA CUGAUGAGGCCGAAAGGCCGAA AUCUUGA	450

687	GCUCCCA CUGAUGAGGCCGAAAGGCCGAA AGUUCCG	451

700	CCCCACC CUGAUGAGGCCGAAAGGCCGAA AGGCAGC	452

715	GCAAGAA CUGAUGAGGCCGAAAGGCCGAA AUCUCAU	453

717	CAGCAAG CUGAUGAGGCCGAAAGGCCGAA AGAUCUC	454

718	ACAGCAA CUGAUGAGGCCGAAAGGCCGAA AAGAUCU	455

721	CGCAAUG CUGAUGAGGCCGAAAGGCCGAA AGGAGAA	456

751	ACACCUC CUGAUGAGGCCGAAAGGCCGAA AUGUCUU	457

759	CGUGAAA CUGAUGAGGCCGAAAGGCCGAA ACACCUC	458

761	CCCGUGA CUGAUGAGGCCGAAAGGCCGAA AUACACC	459

762	UCCCGUG CUGAUGAGGCCGAAAGGCCGAA AAUACAC	460

763	GUCCCGU CUGAUGAGGCCGAAAGGCCGAA AAAUACA	461

792	AGAAAAG CUGAUGAGGCCGAAAGGCCGAA AGCCUCG	462

795	UUGAGAA CUGAUGAGGCCGAAAGGCCGAA AGGAGCC	463

796	CUUGAGA CUGAUGAGGCCGAAAGGCCGAA AAGGAGC	464

797	GCUUGAG CUGAUGAGGCCGAAAGGCCGAA AAAGGAG	465

798	AGCUUGA CUGAUGAGGCCGAAAGGCCGAA AAAAGGA	466

829	GGAACAC CUGAUGAGGCCGAAAGGCCGAA AUGGCCA	467

834	AGUCCGG CUGAUGAGGCCGAAAGGCCGAA ACACAAU	468

835	GAGUCCG CUGAUGAGGCCGAAAGGCCGAA AACACAA	469

845	GCGUACG CUGAUGAGGCCGAAAGGCCGAA AGGAGUC	470

849	GUCGGCG CUGAUGAGGCCGAAAGGCCGAA ACGGAGG	471

872	CGAACAG CUGAUGAGGCCGAAAGGCCGAA AGCCUGG	472

883	GCAUGGA CUGAUGAGGCCGAAAGGCCGAA ACUCGAA	473

885	CUGCAUG CUGAUGAGGCCGAAAGGCCGAA AGACUCG	474

905	CGAUCAG CUGAUGAGGCCGAAAGGCCGAA AGGCCGC	475

906	GCGAUCA CUGAUGAGGCCGAAAGGCCGAA AAGGCCG	476

919	GCUCACU CUGAUGAGGCCGAAAGGCCGAA AGCUCGC	477

936	GUACUGG CUGAUGAGGCCGAAAGGCCGAA ACUCCAU	478

937	AGUACUG CUGAUGAGGCCGAAAGGCCGAA AACUCCA	479

942	UGGCAAG CUGAUGAGGCCGAAAGGCCGAA ACUGGAA	480

953	UCAUGUG CUGAUGAGGCCGAAAGGCCGAA AUGAGGC	481

962	CGGUGGC CUGAUGAGGCCGAAAGGCCGAA AUCAUCU	482

965	GUCUGGC CUGAUGAGGCCGAAAGGCCGAA AGUACUG	483

973	UCUCUUC CUGAUGAGGCCGAAAGGCCGAA AUCCGGU	484

986	ACUCUUG CUGAUGAGGCCGAAAGGCCGAA AGGUCUC	485

1005	ACUCUUG CUGAUGAGGCCGAAAGGCCGAA AGGUCUC	486

1006	UACUCUU CUGAUGAGGCCGAAAGGCCGAA AAGGUCU	487

1015	UCUUCAU CUGAUGAGGCCGAAAGGCCGAA AUACUCU	488

1028	UUGAAAG CUGAUGAGGCCGAAAGGCCGAA ACUCUUC	490

1031	CCAUUGA CUGAUGAGGCCGAAAGGCCGAA AGGACUC	491

1032	UCCAUGG CUGAUGAGGCCGAAAGGCCGAA AAGGACU	492

1033	GUCCAUU CUGAUGAGGCCGAAAGGCCGAA AAAGGAC	493

1058	CGGGUUG CUGAUGAGGCCGAAAGGCCGAA AGGCCGG	494

1064	UUGGAUC CUGAUGAGGCCGAAAGGCCGAA AGGUGUA	495

1072	GCACAGC CUGAUGAGGCCGAAAGGCCGAA AUACGCC	496

1082	UUUCGGG CUGAUGAGGCCGAAAGGCCGAA AGGCACA	497

1083	ACUUCGG CUGAUGAGGCCGAAAGGCCGAA AAGGCUU	498

1092	AGAAGUU CUGAUGAGGCCGAAAGGCCGAA AGUUUCG	499

1097	GGGACAG CUGAUGAGGCCGAAAGGCCGAA AGUUGAG	500

1098	GGGGACA CUGAUGAGGCCGAAAGGCCGAA AAGUUGA	501

1102	GCUUGGG CUGAUGAGGCCGAAAGGCCGAA ACAGAAG	502

1125	GAAGGUG CUGAUGAGGCCGAAAGGCCGAA AGGGCUG	503

1127	GUAAGGC CUGAUGAGGCCGAAAGGCCGAA AUAUGGC	504

1131	UGGUGCU CUGAUGAGGCCGAAAGGCCGAA AGGGAUG	505

1132	AUGCUGG CUGAUGAGGCCGAAAGGCCGAA AAGGUGU	506

1133	GAAGCUG CUGAUGAGGCCGAAAGGCCGAA AGAUGGA	507

1137	GCGCGCU CUGAUGAGGCCGAAAGGCCGAA AAGUAAA	508

1140	GCUGAGG CUGAUGAGGCCGAAAGGCCGAA AUGCUGG	509

1153	CAAAGUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGC	510

1158	CUCAUCA CUGAUGAGGCCGAAAGGCCGAA AGUUGAU	511

1167	GGGGGAA CUGAUGAGGCCGAAAGGCCGAA ACUCAUC	512

1168	UGGGGGA CUGAUGAGGCCGAAAGGCCGAA AACUCAU	513

1169	AUGGGGG CUGAUGAGGCCGAAAGGCCGAA AAACUCA	514

1182	UGAUGGU CUGAUGAGGCCGAAAGGCCGAA ACAGCAU	515

1183	CUGAUGG CUGAUGAGGCCGAAAGGCCGAA AACAGCA	516

1184	UCAGGAG CUGAUGAGGCCGAAAGGCCGAA AGGGGCC	517

1187	GGCUGAG CUGAUGAGGCCGAAAGGCCGAA AAGGGAC	518

1188	CUGCCCU CUGAUGAGGCCGAAAGGCCGAA AUGGUAA	519

1198	UCAGACU CUGAUGAGGCCGAAAGGCCGAA AACUCCC	520

1209	GAAGGUG CUGAUGAGGCCGAAAGGCCGAA AGGGCUG	521

1215	CGGUGCU CUGAUGAGGCCGAAAGGCCGAA AGGCCAG	522

1229	GCUGAGG CUGAUGAGGCCGAAAGGCCGAA AGGGACC	523

1237	GGGGCAG CUGAUGAGGCCGAAAGGCCGAA AGCUGGG	524

1250	GAGCCUG CUGAUGAGGCCGAAAGGCCGAA AGGCUGG	525

1268	GGGGCAG CUGAUGAGGCCGAAAGGCCGAA AGCUGGG	526

1279	AGGAAGG CUGAUGAGGCCGAAAGGCCGAA ACCAUGG	527

1281	CGCAGCU CUGAUGAGGCCGAAAGGCCGAA AGCCCAC	528

1286	UGGGGGA CUGAUGAGGCCGAAAGGCCGAA AACUCAU	529

1309	AGACUCG CUGAUGAGGCCGAAAGGCCGAA ACAGGAG	530

1315	GGGUUAG CUGAUGAGGCCGAAAGGCCGAA ACUGGGG	531

1318	CCGGGGU CUGAUGAGGCCGAAAGGCCGAA AGAACUG	532

1331	GACUGGG CUGAUGAGGCCGAAAGGCCGAA AGGACCC	533

1334	UCAGCUU CUGAUGAGGCCGAAAGGCCGAA AGAAAAG	534

1389	GGCUUCC CUGAUGAGGCCGAAAGGCCGAA ACAGCGU	535

1413	AGCAUCA CUGAUGAGGCCGAAAGGCCGAA ACUGGAG	536

1414	CAGCAUC CUGAUGAGGCCGAAAGGCCGAA AACUGCA	537

1437	GCCAAGC CUGAUGAGGCCGAAAGGCCGAA AGGCCCC	538

1441	UGUUGCC CUGAUGAGGCCGAAAGGCCGAA AGCAAGG	539

1467	GUCUGUG CUGAUGAGGCCGAAAGGCCGAA ACACUCC	540

1468	GGUCUGU CUGAUGAGGCCGAAAGGCCGAA AACACUC	541

1482	GUCCACA CUGAUGAGGCCGAAAGGCCGAA AUGCCAG	542

1486	AGUUCCC CUGAUGAGGCCGAAAGGCCGAA ACCGAAG	543

1494	AAACUCU CUGAUGAGGCCGAAAGGCCGAA AGUUGUC	544

1500	CUGCUGA CUGAUGAGGCCGAAAGGCCGAA ACUCUGA	545

1501	GCUGCUG CUGAUGAGGCCGAAAGGCCGAA AACUCUG	546

1502	AGCUGCU CUGAUGAGGCCGAAAGGCCGAA AAACUCU	547

1525	ACACAGG CUGAUGAGGCCGAAAGGCCGAA AUGCACC	548

1566	UUCAGGG CUGAUGAGGCCGAAAGGCCGAA ACUCCAU	549

1577	CGAGUUA CUGAUGAGGCCGAAAGGCCGAA AGCUUCA	550

1579	GGCGAGU CUGAUGAGGCCGAAAGGCCGAA AUAGCUU	551

1583	ACCAGGC CUGAUGAGGCCGAAAGGCCGAA AGUUAUA	552

1588	CCCUCUC CUGAUGAGGCCGAAAGGCCGAA AGGAGAG	553

1622	GGGGCAG CUGAUGAGGCCGAAAGGCCGAA AGCUGGG	554

1628	CCUACCG CUGAUGAGGCCGAAAGGCCGAA AGCAGGA	555

1648	CAUUGGG CUGAUGAGGCCGAAAGGCCGAA AGCCCCG	556

1660	CUGGGCA CUGAUGAGGCCGAAAGGCCGAA AGGUCAG	557

1663	CACCUGG CUGAUGAGGCCGAAAGGCCGAA AGCAGAG	558

1664	UCACCUG CUGAUGAGGCCGAAAGGCCGAA AAGCAGA	559

1665	ACCUCCG CUGAUGAGGCCGAAAGGCCGAA AAGCGAG	560

1680	GGAGGAG CUGAUGAGGCCGAAAGGCCGAA AGUCUUC	561

1681	UGGAGGA CUGAUGAGGCCGAAAGGCCGAA AAGUCUU	562

1683	AAUGGAG CUGAUGAGGCCGAAAGGCCGAA AGAAGUC	563

1686	CGCAAUG CUGAUGAGGCCGAAAGGCCGAA AGGAGAA	564

1690	UGUCCGC CUGAUGAGGCCGAAAGGCCGAA AUGGAGG	565

1704	AGCAGAG CUGAUGAGGCCGAAAGGCCGAA AGUCCAU	566

1705	GAGCAGA CUGAUGAGGCCGAAAGGCCGAA AAGUCCA	567

1707	AAGAGCA CUGAUGAGGCCGAAAGGCCGAA AGAAGUC	568

1721	CUGAUCU CUGAUGAGGCCGAAAGGCCGAA ACUCAAA	569

1726	AGGAGCU CUGAUGAGGCCGAAAGGCCGAA AUCUGAC	570

1731	ACCUUAG CUGAUGAGGCCGAAAGGCCGAA AGCUGAU	571

1734	AGCACCU CUGAUGAGGCCGAAAGGCCGAA AGGAGCU	572

1754	CUCUUGG CUGAUGAGGCCGAAAGGCCGAA AGCACUG	573

TABLE V


Human rel A HH Ribozyme Sequences

nt.
Sequence	HH Ribozyme Sequence	SEQ ID NO.

19	UACAGAC CUGAUGAGGCCGAAAGGCCGAA AGCCAUU	574

22	CACUACA CUGAUGAGGCCGAAAGGCCGAA ACGAGCC	575

26	CGUGCAC CUGAUGAGGCCGAAAGGCCGAA ACAGACG	576

93	GAGGGGG CUGAUGAGGCCGAAAGGCCGAA ACAGUUC	577

94	UGAGGGG CUGAUGAGGCCGAAAGGCCGAA AACAGUU	578

100	GGAAGAU CUGAUGAGGCCGAAAGGCCGAA AGGGGGA	579

103	CCGGGAA CUGAUGAGGCCGAAAGGCCGAA AUGAGGG	580

105	UGCCGGG CUGAUGAGGCCGAAAGGCCGAA AGAUGAG	581

106	CUGCCGG CUGAUGAGGCCGAAAGGCCGAA AAGAUGA	582

129	GGGGCCA CUGAUGAGGCCGAAAGGCCGAA AGGCCUG	583

138	CUCCACA CUGAUGAGGCCGAAAGGCCGAA AGGGGCC	584

148	GCUCAAU CUGAUGAGGCCGAAAGGCCGAA AUCUCCA	585

151	GCUGCUC CUGAUGAGGCCGAAAGGCCGAA AUGAUCU	586

180	GUAGCGG CUGAUGAGGCCGAAAGGCCGAA AGCGCAU	587

181	UGUAGCG CUGAUGAGGCCGAAAGGCCGAA AAGCGCA	588

186	GCACUUG CUGAUGAGGCCGAAAGGCCGAA AGCGGAA	589

204	GCCCGCG CUGAUGAGGCCGAAAGGCCGAA AGCGCCC	590

217	CGCCUGG CUGAUGAGGCCGAAAGGCCGAA AUGCUGC	591

239	UUGGUGG CUGAUGAGGCCGAAAGGCCGAA AUCUGUG	592

262	UGAUCUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGG	593

268	AGCCAUU CUGAUGAGGCCGAAAGGCCGAA AUCUUGA	594

276	UCCUGUG CUGAUGAGGCCGAAAGGCCGAA AGCCAUU	595

301	CCAGGGA CUGAUGAGGCCGAAAGGCCGAA AUGCGCA	596

303	GACCAGG CUGAUGAGGCCGAAAGGCCGAA AGAUGCG	597

310	CCUUGGU CUGAUGAGGCCGAAAGGCCGAA ACCAGGG	598

323	CGGUGAG CUGAUGAGGCCGAAAGGCCGAA AGGGUCC	599

326	GGCCGGU CUGAUGAGGCCGAAAGGCCGAA AGGAGGG	600

335	UGGGGGU CUGAUGAGGCCGAAAGGCCGAA AGGCCGG	601

349	UUCCUAC CUGAUGAGGCCGAAAGGCCGAA AGCUCGU	602

352	CCUUUCC CUGAUGAGGCCGAAAGGCCGAA ACAAGCU	603

375	CUCAUAG CUGAUGAGGCCGAAAGGCCGAA AGCCAUC	604

376	CCUCAUA CUGAUGAGGCCGAAAGGCCGAA AAGCCAU	605

378	AGCCUCA CUGAUGAGGCCGAAAGGCCGAA AGAAGCC	606

391	CCGGGCA CUGAUGAGGCCGAAAGGCCGAA AGCUCAG	607

409	AACUGUG CUGAUGAGGCCGAAAGGCCGAA AUGCAGC	608

416	UUCUGGA CUGAUGAGGCCGAAAGGCCGAA ACUGUGG	609

417	GUUCUGG CUGAUGAGGCCGAAAGGCCGAA AACUGUG	610

418	GGUUCUG CUGAUGAGGCCGAAAGGCCGAA AAACUGU	611

433	CACACUG CUGAUGAGGCCGAAAGGCCGAA AUUCCCA	612

467	UGACUGA CUGAUGAGGCCGAAAGGCCGAA AGCCUGC	613

469	GCUGACU CUGAUGAGGCCGAAAGGCCGAA AUAGCCU	614

473	AUGCGCU CUGAUGAGGCCGAAAGGCCGAA ACUGAUA	615

481	UGGUCUG CUGAUGAGGCCGAAAGGCCGAA AUGCGCU	616

501	AACUUGG CUGAUGAGGCCGAAAGGCCGAA AGGGGUU	617

502	GAACUUG CUGAUGAGGCCGAAAGGCCGAA AAGGGGU	618

508	CUAUAGG CUGAUGAGGCCGAAAGGCCGAA ACUUGAA	619

509	UCUAUAG CUGAUGAGGCCGAAAGGCCGAA AACUUGG	620

512	UCUUCUA CUGAUGAGGCCGAAAGGCCGAA AGGAACU	621

514	GCUCUUC CUGAUGAGGCCGAAAGGCCGAA AUAGGAA	622

534	CAGGUCG CUGAUGAGGCCGAAAGGCCGAA AGUCCCC	623

556	GGAAGCA CUGAUGAGGCCGAAAGGCCGAA AGCCGCA	624

561	CACCUGG CUGAUGAGGCCGAAAGGCCGAA AGCAGAG	625

562	UCACCUG CUGAUGAGGCCGAAAGGCCGAA AAGCAGA	626

585	CCUGCCU CUGAUGAGGCCGAAAGGCCGAA AUGGGUC	627

598	GCAGGCG CUGAUGAGGCCGAAAGGCCGAA AGGGGCC	628

613	GAGGAAG CUGAUGAGGCCGAAAGGCCGAA ACAGGCG	629

616	GAUGAGG CUGAUGAGGCCGAAAGGCCGAA AGGACAG	630

617	GGAUGAG CUGAUGAGGCCGAAAGGCCGAA AAGGACA	631

620	AUGGGAU CUGAUGAGGCCGAAAGGCCGAA AGGAAGG	632

623	AAGAUGG CUGAUGAGGCCGAAAGGCCGAA AUGAGGA	633

628	UGUCAAA CUGAUGAGGCCGAAAGGCCGAA AUCGGAU	634

630	AUUGUCA CUGAUGAGGCCGAAAGGCCGAA AGAUGGG	635

631	GAUUGUC CUGAUGAGGCCGAAAGGCCGAA AAGAUGG	636

638	GGGGCAC CUGAUGAGGCCGAAAGGCCGAA AUUGUCA	637

661	AGAUCUU CUGAUGAGGCCGAAAGGCCGAA AGCUCGG	638

667	CUCGGCA CUGAUGAGGCCGAAAGGCCGAA AUCUUGA	639

687	GCUGCCA CUGAUGAGGCCGAAAGGCCGAA AGUUUCG	640

700	CCCCACC CUGAUGAGGCCGAAAGGCCGAA AGGCAGC	641

715	GUAGGAA CUGAUGAGGCCGAAAGGCCGAA AUCUCAU	642

717	CAGUAAG CUGAUGAGGCCGAAAGGCCGAA AGAUCUC	643

718	ACAGUAG CUGAUGAGGCCGAAAGGCCGAA AAGAUCU	644

721	CACACAG CUGAUGAGGCCGAAAGGCCGAA AGGAAGA	645

751	ACACCUC CUGAUGAGGCCGAAAGGCCGAA AUGUCCU	646

759	CGUGAAA CUGAUGAGGCCGAAAGGCCGAA ACACCUC	647

761	CCCGUGA CUGAUGAGGCCGAAAGGCCGAA AUACACC	648

762	UCCCGUG CUGAUGAGGCCGAAAGGCCGAA AAUACAC	649

763	GUCCCGU CUGAUGAGGCCGAAAGGCCGAA AAAUACA	650

792	CGAAAAG CUGAUGAGGCCGAAAGGCCGAA AGCCUCG	651

795	UUGCGAA CUGAUGAGGCCGAAAGGCCGAA AGGAGCC	652

796	CUUGCGA CUGAUGAGGCCGAAAGGCCGAA AAGGAGC	653

797	GCUUGCG CUGAUGAGGCCGAAAGGCCGAA AAAGGAG	654

798	AGCUUGC CUGAUGAGGCCGAAAGGCCGAA AAAAGGA	655

829	GGAACAC CUGAUGAGGCCGAAAGGCCGAA AUGGCCA	656

834	GGUCCGG CUGAUGAGGCCGAAAGGCCGAA ACACAAU	657

835	GGGUCCG CUGAUGAGGCCGAAAGGCCGAA AACACAA	658

845	GCGUAGG CUGAUGAGGCCGAAAGGCCGAA AGGGGUC	659

849	GUCUGCG CUGAUGAGGCCGAAAGGCCGAA AGGGAGG	660

872	CGCACAG CUGAUGAGGCCGAAAGGCCGAA AGCCUGC	661

883	GCAUGGA CUGAUGAGGCCGAAAGGCCGAA ACACGCA	662

885	CUGCAUG CUGAUGAGGCCGAAAGGCCGAA AGACACG	662

905	CGGUCGG CUGAUGAGGCCGAAAGGCCGAA AGGCCGC	664

906	CCGGUCG CUGAUGAGGCCGAAAGGCCGAA AAGGCCG	665

919	GCUCAGU CUGAUGAGGCCGAAAGGCCGAA AGCUCCC	666

936	GUACUGG CUGAUGAGGCCGAAAGGCCGAA AUUCCAU	667

937	GGUACUG CUGAUGAGGCCGAAAGGCCGAA AAUUCCA	668

942	UGGCAGG CUGAUGAGGCCGAAAGGCCGAA ACUGGAA	669

953	UCGUCUG CUGAUGAGGCCGAAAGGCCGAA AUCUGGC	670

962	CGGUGAC CUGAUGAGGCCGAAAGGCCGAA AUCGUCU	671

965	AUCCGGU CUGAUGAGGCCGAAAGGCCGAA ACGAUCG	672

973	UCUCCUC CUGAUGAGGCCGAAAGGCCGAA AUCCGGU	673

986	GUCCUUU CUGAUGAGGCCGAAAGGCCGAA AGGUUUC	674

996	GGUCUCA CUGAUGAGGCCGAAAGGCCGAA AUGUCCU	675

1005	GCUCUUG CUGAUGAGGCCGAAAGGCCGAA AGGUCUC	676

1006	UGCUCUU CUGAUGAGGCCGAAAGGCCGAA AAGGUCU	677

1015	UCUUCAU CUGAUGAGGCCGAAAGGCCGAA AUGCUCU	678

1028	CUGAAAG CUGAUGAGGCCGAAAGGCCGAA ACUCUUC	679

1031	CCGCUGA CUGAUGAGGCCGAAAGGCCGAA AGGACUC	680

1032	UCCGCUG CUGAUGAGGCCGAAAGGCCGAA AAGGACU	681

1033	GUCCGCU CUGAUGAGGCCGAAAGGCCGAA AAAGGAC	682

1058	CGAGGUG CUGAUGAGGCCGAAAGGCCGAA AGGCCGG	683

1064	AUGCGUC CUGAUGAGGCCGAAAGGCCGAA AGGUGGA	684

1072	GCACAGC CUGAUGAGGCCGAAAGGCCGAA AUGCGUC	685

1082	CUGCGGG CUGAUGAGGCCGAAAGGCCGAA AGGCACA	686

1083	GCUGCGG CUGAUGAGGCCGAAAGGCCGAA AAGGCAC	687

1092	AGAAGCU CUGAUGAGGCCGAAAGGCCGAA AGCUGCG	688

1097	GGGACAG CUGAUGAGGCCGAAAGGCCGAA AGCUGAG	689

1098	GGGGACA CUGAUGAGGCCGAAAGGCCGAA AAGCUGA	690

1102	GCUUGGG CUGAUGAGGCCGAAAGGCCGAA ACAGAAG	691

1125	AAAGGGA CUGAUGAGGCCGAAAGGCCGAA AGGGCUG	692

1127	GUAAAGG CUGAUGAGGCCGAAAGGCCGAA AUAGGGC	693

1131	UGACGUA CUGAUGAGGCCGAAAGGCCGAA AGGGAUA	694

1132	AUGACGU CUGAUGAGGCCGAAAGGCCGAA AAGGGAU	695

1133	GAUGACG CUGAUGAGGCCGAAAGGCCGAA AAAGGGA	696

1137	CAGGGAU CUGAUGAGGCCGAAAGGCCGAA ACGUAAA	697

1140	GCUCAGG CUGAUGAGGCCGAAAGGCCGAA AUGACGU	698

1153	CAUAGUU CUGAUGAGGCCGAAAGGCCGAA AUGGUGC	699

1158	CUCAUCA CUGAUGAGGCCGAAAGGCCGAA AGUUGAU	700

1167	GGUGGGA CUGAUGAGGCCGAAAGGCCGAA ACUCAUC	701

1168	UGGUGGG CUGAUGAGGCCGAAAGGCCGAA AACUCAU	702

1169	AUGGUGG CUGAUGAGGCCGAAAGGCCGAA AAACUCA	703

1182	AGAAGGA CUGAUGAGGCCGAAAGGCCGAA ACACCAU	704

1183	CAGAAGG CUGAUGAGGCCGAAAGGCCGAA AACACCA	705

1184	CCAGAAG CUGAUGAGGCCGAAAGGCCGAA AAACACC	706

1187	UGCCCAG CUGAUGAGGCCGAAAGGCCGAA AAGAAAC	707

1188	CUGCCCA CUGAUGAGGCCGAAAGGCCGAA AAGGAAA	708

1198	CCUGGCU CUGAUGAGGCCGAAAGGCCGAA AUCUGCC	709

1209	GAAGGCC CUGAUGAGGCCGAAAGGCCGAA AGGCCUG	710

1215	CGGGGCC CUGAUGAGGCCGAAAGGCCGAA AGGCCGA	711

1229	ACUUGGG CUGAUGAGGCCGAAAGGCCGAA AGGGGCC	712

1237	GGGGCAG CUGAUGAGGCCGAAAGGCCGAA ACUUGGG	713

1250	GGGGCUG CUGAUGAGGCCGAAAGGCCGAA AGCCUGG	714

1268	AUGGCUG CUGAUGAGGCCGAAAGGCCGAA AGCAGGG	715

1279	GAGCUGA CUGAUGAGGCCGAAAGGCCGAA ACCAUGG	716

1281	CAGAGCU CUGAUGAGGCCGAAAGGCCGAA AUACCAU	717

1286	UGGGCCA CUGAUGAGGCCGAAAGGCCGAA AGCUGAU	718

1309	GGACUGG CUGAUGAGGCCGAAAGGCCGAA ACAGGGG	719

1315	GGGCUAG CUGAUGAGGCCGAAAGGCCGAA ACUGGGA	720

1318	CUGGGGC CUGAUGAGGCCGAAAGGCCGAA AGGACUG	721

1331	GCCUGAG CUGAUGAGGCCGAAAGGCCGAA AGGGCCU	722

1334	ACAGCCU CUGAUGAGGCCGAAAGGCCGAA AGGAGGG	723

1389	GGCCUCU CUGAUGAGGCCGAAAGGCCGAA ACAGCGU	724

1413	AUCAUCA CUGAUGAGGCCGAAAGGCCGAA ACUGCAG	725

1414	CAUCAUC CUGAUGAGGCCGAAAGGCCGAA AACUGCA	726

1437	GCCAAGC CUGAUGAGGCCGAAAGGCCGAA AGGCCCC	727

1441	UGUUGCC CUGAUGAGGCCGAAAGGCCGAA AGCAAGG	728

1467	GUCUGUG CUGAUGAGGCCGAAAGGCCGAA ACACAGC	729

1468	GGUCUGU CUGAUGAGGCCGAAAGGCCGAA AACACAG	730

1482	GUCGACG CUGAUGAGGCCGAAAGGCCGAA AUGCCAG	731

1486	AGUUGUC CUGAUGAGGCCGAAAGGCCGAA ACGGAUG	732

1494	AAACUCG CUGAUGAGGCCGAAAGGCCGAA AGUUGUC	733

1500	CUGCUGA CUGAUGAGGCCGAAAGGCCGAA ACUCGGA	734

1501	GCUGCUG CUGAUGAGGCCGAAAGGCCGAA AACUCGG	735

1502	AGCUGCU CUGAUGAGGCCGAAAGGCCGAA AAACUCG	736

1525	CCACAGG CUGAUGAGGCCGAAAGGCCGAA AUGCCCU	737

1566	CACAGGG CUGAUGAGGCCGAAAGGCCGAA ACUCCAU	738

1577	CGAGUUA CUGAUGAGGCCGAAAGGCCGAA AGCCUCA	739

1579	GGCGAGU CUGAUGAGGCCGAAAGGCCGAA AUAGCCU	740

1583	ACCAGGC CUGAUGAGGCCGAAAGGCCGAA AGUUAUA	741

1588	CUGUCAC CUGAUGAGGCCGAAAGGCCGAA AGGCGAG	742

1622	GGAGCAG CUGAUGAGGCCGAAAGGCCGAA AGCUGGG	743

1628	CCCAGUG CUGAUGAGGCCGAAAGGCCGAA AGCAGGA	744

1648	CAUUGGG CUGAUGAGGCCGAAAGGCCGAA AGCCCCG	745

1660	CUGAAAG CUGAUGAGGCCGAAAGGCCGAA AGGCCAU	746

1663	CUCCUGA CUGAUGAGGCCGAAAGGCCGAA AGGAGGC	747

1664	UCUCCUG CUGAUGAGGCCGAAAGGCCGAA AAGGAGG	748

1665	AUCUCCU CUGAUGAGGCCGAAAGGCCGAA AAAGGAG	749

1680	GGAGGAG CUGAUGAGGCCGAAAGGCCGAA AGUCUUC	750

1681	UGGAGGA CUGAUGAGGCCGAAAGGCCGAA AAGUGUU	751

1683	AAUGGAG CUGAUGAGGCCGAAAGGCCGAA AGAAGUC	752

1686	CGCAAUG CUGAUGAGGCCGAAAGGCCGAA AGGAGAA	753

1690	UGUCCGC CUGAUGAGGCCGAAAGGCCGAA AUGGAGG	754

1704	GGCUGAG CUGAUGAGGCCGAAAGGCCGAA AGUCCAU	755

1705	GGGCUGA CUGAUGAGGCCGAAAGGCCGAA AAGUCCA	756

1707	CAGGGCU CUGAUGAGGCCGAAAGGCCGAA AGAAGUC	757

1721	CUGAUCU CUGAUGAGGCCGAAAGGCCGAA ACUCAGC	758

1726	AGGAGCU CUGAUGAGGCCGAAAGGCCGAA AUCUGAC	759

1731	CCCUUAG CUGAUGAGGCCGAAAGGCCGAA AGCUGAU	760

1734	ACCCCCU CUGAUGAGGCCGAAAGGCCGAA AGGAGCU	761

1754	CUCUGGG CUGAUGAGGCCGAAAGGCCGAA AGGGCAG	762

TABLE VI


Human rel A Hairpin Ribozyme/Target Sequences

nt.		Seq ID		Seq ID
Position	Hairpin Ribozyme sequence	No.	Substrate	No.

90	UGAGGGGG AGAA GUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	763	GAACU GUU CCCCCUCA	778

156	GCUGCUUG AGAA GCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	764	GAGCA GCC CAAGCAGC	779

362	GCCAUCCC AGAA GUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	765	GGACU GCC GGGAUGGC	780

413	GUUCUGGA AGAA GUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	766	CCACA GUU UCCAGAAC	781

606	GAAGGACA AGAA GCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	767	CUGCC GCC UGUCCUUC	782

652	UUGAGCUC AGAA GUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	768	ACACU GCC GAGCUCAA	783

695	CCCACCGA AGAA GCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	769	CAGCU GCC UCGGUGGG	784

853	AGGCUGGG AGAA GCGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	770	ACGCA GAC CCCAGCCU	785

900	GGUCGGAA AGAA GCCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	771	CGGCG GCC UUCCGACC	786

955	UGACGAUC AGAA GUAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	772	AUACA GAC GAUCGUCA	787

1037	GUCGGUGG AGAA GCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	773	CAGCG GAC CCACCGAC	788

1045	GGCCGGGG AGAA GUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	774	CCACC GAC CCCCGGCC	789

1410	CAUCAUCA AGAA GCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	775	CUGCA GUU UGAUGAUG	790

1453	ACAGCUGG AGAA GUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	776	GCACA GAC CCAGCUGU	791

1471	GAUGCCAG AGAA GUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	777	UCACA GAC CUGGCAUC	792

TABLE VII


Mouse rel A Hairpin Ribozyme/Target Sequences

nt.		Seq. ID		Seq. ID
Position	Hairpin Ribozyme sequence	No.	Substrate	No.

137	GUUGCUUC AGAA GUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	793	GAACA GCC GAAGCAAC	812

273	GAGAUUCG AGAA GUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	794	GAACA GUU CGAAUCUC	813

343	GCCAUCCC AGAA GUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	795	GGACU GCC GGGAUGGC	814

366	GGGCAGAG AGAA GCCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	796	AGGCU GAC CUCUGCCC	815

633	UUGAGCUC AGAA GUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	797	ACACU GCC GAGCUCAA	816

676	CCCACCGA AGAA GCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	798	GAGCU GCC UCGGUGGG	817

834	AGGCUGGG AGAA GCGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	799	ACGCC GAC CCCAGCCU	818

881	GAUCAGAA AGAA GCCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	800	CGGCG GCC UUCUGAUC	819

1100	AGGUGUAG AGAA GCGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	801	CCGCA GCC CUACACCU	820

1205	GGGCAGAG AGAA GUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	802	GCACC GUC CUCUGCCC	821

1361	GGGCUUCC AGAA GCGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	803	ACGCU GUC GGAAGCCC	822

1385	CAGCAUCA AGAA GCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	804	CUGCA GUU UGAUGCUG	823

1431	ACUCCUGG AGAA GUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	805	GCACA GAC CCAGGAGU	824

1449	GAUGCCAG AGAA GUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	806	UCACA GAC CUGGCAUC	825

1802	AAGUCGGG AGAA GCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	807	CAGCU GCC CCCGACUU	826

2009	UGGCUCCA AGAA GUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	808	GGACA GAC UGGAGCCA	827

2124	UGGUGUCG AGAA GCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	809	GUGCU GCC CGACACCA	828

2233	AUUCUGAA AGAA GCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	810	UGGCC GCC UUCAGAAU	829

2354	UCAGUAAA AGAA GUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA	811	AGACA GCC UUUACUGA	830

[0076]
1 830 11 nucleic acid single linear The letter “N” stands for any base. “H” represents nucleotide C, A, or U. 1 NNNNUHNNNN N 11 32 nucleic acid single linear The letter “N” stands for any base. 2 NNNNNCUGAN GAGNNNNNNN NNNCGAAANN NN 32 14 nucleic acid single linear The letter “N” stands for any base. 3 NNNNNGUCNN NNNN 14 50 nucleic acid single linear The letter “N” stands for any base. 4 NNNNNNAGAA NNNNACCAGA GAAACACACG UUGUGGUAUA UUACCUGGUA 50 85 nucleic acid single linear 5 UGGCCGGCAU GGUCCCAGCC UCCUCGCUGG CGCCGGCUGG GCAACAUUCC GAGGGGACCG 60 UCCCCUCGGU AAUGGCGAAU GGGAC 85 176 nucleic acid single linear 6 GGGAAAGCUU GCGAAGGGCG UCGUCGCCCC GAGCGGUAGU AAGCAGGGAA CUCACCUCCA 60 AUUUCAGUAC UGAAAUUGUC GUAGCAGUUG ACUACUGUUA UGUGAUUGGU AGAGGCUAAG 120 UGACGGUAUU GGCGUAAGUC AGUAUUGCAG CACAGCACAA GCCCGCUUGC GAGAAU 176 15 base pairs nucleic acid single linear 7 AAUGGCUACA CAGGA 15 15 base pairs nucleic acid single linear 8 AGCUCCUACG UGGUG 15 15 base pairs nucleic acid single linear 9 CCUCCAUUGC GGACA 15 15 base pairs nucleic acid single linear 10 GAUCUGUUUC CCCUC 15 15 base pairs nucleic acid single linear 11 AUCUGUUUCC CCUCA 15 15 base pairs nucleic acid single linear 12 UUCCCCUCAU CUUUC 15 15 base pairs nucleic acid single linear 13 CCCUCAUCUU UCCCU 15 15 base pairs nucleic acid single linear 14 CUCAUCUUUC CCUCA 15 15 base pairs nucleic acid single linear 15 UCAUCUUUCC CUCAG 15 15 base pairs nucleic acid single linear 16 CAGGCUUCUG GGCCU 15 15 base pairs nucleic acid single linear 17 GGGCCUUAUG UGGAG 15 15 base pairs nucleic acid single linear 18 UGGAGAUCAU CGAAC 15 15 base pairs nucleic acid single linear 19 AGAUCAUCGA ACAGC 15 15 base pairs nucleic acid single linear 20 AUGCGAUUCC GCUAU 15 15 base pairs nucleic acid single linear 21 UGCGAUUCCG CUAUA 15 15 base pairs nucleic acid single linear 22 UUCCGCUAUA AAUGC 15 15 base pairs nucleic acid single linear 23 GGGCGCUCAG CGGGC 15 15 base pairs nucleic acid single linear 24 GCAGUAUUCC UGGCG 15 15 base pairs nucleic acid single linear 25 CACAGAUACC ACCAA 15 15 base pairs nucleic acid single linear 26 CCACCAUCAA GAUCA 15 15 base pairs nucleic acid single linear 27 UCAAGAUCAA UGGCU 15 15 base pairs nucleic acid single linear 28 AAUGGCUACA CAGGA 15 15 base pairs nucleic acid single linear 29 UUCGAAUCUC CCUGG 15 15 base pairs nucleic acid single linear 30 CGAAUCUCCC UGGUC 15 15 base pairs nucleic acid single linear 31 CCCUGGUCAC CAAGG 15 15 base pairs nucleic acid single linear 32 GGCCCCUCCU CCUGA 15 15 base pairs nucleic acid single linear 33 UCCACCUCAC CGGCC 15 15 base pairs nucleic acid single linear 34 CCGGCCUCAU CCACA 15 15 base pairs nucleic acid single linear 35 AUGAACUUGU GGGGA 15 15 base pairs nucleic acid single linear 36 AGAUCAUCGA ACAGC 15 15 base pairs nucleic acid single linear 37 GAUGGCUACU AUGAG 15 15 base pairs nucleic acid single linear 38 AUGGUCUCUC CGGAG 15 15 base pairs nucleic acid single linear 39 GGCUACUAUG AGGCU 15 15 base pairs nucleic acid single linear 40 CUGACCUCUG CCCAG 15 15 base pairs nucleic acid single linear 41 GCAGUAUCCA UAGCU 15 15 base pairs nucleic acid single linear 42 CCGCAGUAUC CAUAG 15 15 base pairs nucleic acid single linear 43 CAUAGCUUCC AGAAC 15 15 base pairs nucleic acid single linear 44 AUAGCUUCCA GAACC 15 15 base pairs nucleic acid single linear 45 UGGGGAUCCA GUGUG 15 15 base pairs nucleic acid single linear 46 GGCUCCUUUU CUCAA 15 15 base pairs nucleic acid single linear 47 GCUCCUUUUC UCAAG 15 15 base pairs nucleic acid single linear 48 CUCCUUUUCU CAAGC 15 15 base pairs nucleic acid single linear 49 UCCUUUUCUC AAGCU 15 15 base pairs nucleic acid single linear 50 UGGCCAUUGU GUUCC 15 15 base pairs nucleic acid single linear 51 AUUGUGUUCC GGACU 15 15 base pairs nucleic acid single linear 52 UUGUGUUCCG GACUC 15 15 base pairs nucleic acid single linear 53 GACUCCUCCG UACGC 15 15 base pairs nucleic acid single linear 54 CCUCCGUACG CCGAC 15 15 base pairs nucleic acid single linear 55 CCAGGCUCCU GUUCG 15 15 base pairs nucleic acid single linear 56 UUCGAGUCUC CAUGC 15 15 base pairs nucleic acid single linear 57 CGAGUCUCCA UGCAG 15 15 base pairs nucleic acid single linear 58 GCGGCCUUCU GAUCG 15 15 base pairs nucleic acid single linear 59 CGGCCUUCUG AUCGC 15 15 base pairs nucleic acid single linear 60 GCGAGCUCAG UGAGC 15 15 base pairs nucleic acid single linear 61 AUGGAGUUCC AGUAC 15 15 base pairs nucleic acid single linear 62 UGGAGUUCCA GUACU 15 15 base pairs nucleic acid single linear 63 UUCCAGUACU UGCCA 15 15 base pairs nucleic acid single linear 64 GCCUCAUCCA CAUGA 15 15 base pairs nucleic acid single linear 65 AGAUGAUCGC CACCG 15 15 base pairs nucleic acid single linear 66 CAGUACUUGC CAGAC 15 15 base pairs nucleic acid single linear 67 ACCGGAUUGA AGAGA 15 15 base pairs nucleic acid single linear 68 GAGACCUUCA AGAGU 15 15 base pairs nucleic acid single linear 69 AGGACCUAUG AGACC 15 15 base pairs nucleic acid single linear 70 GAGACCUUCA AGAGU 15 15 base pairs nucleic acid single linear 71 AGACCUUCAA GAGUA 15 15 base pairs nucleic acid single linear 72 AGAGUAUCAU GAAGA 15 15 base pairs nucleic acid single linear 73 GAAGAGUCCU UUCAA 15 15 base pairs nucleic acid single linear 74 GAGUCCUUUC AAUGG 15 15 base pairs nucleic acid single linear 75 AGUCCUUUCA AUGGA 15 15 base pairs nucleic acid single linear 76 GUCCUUUCAA UGGAC 15 15 base pairs nucleic acid single linear 77 CCGGCCUCCA ACCCG 15 15 base pairs nucleic acid single linear 78 UACACCUUGA UCCAA 15 15 base pairs nucleic acid single linear 79 GGCGUAUUGC UGUGC 15 15 base pairs nucleic acid single linear 80 UGUGCCUACC CGAAA 15 15 base pairs nucleic acid single linear 81 AAGCCUUCCC GAAGU 15 15 base pairs nucleic acid single linear 82 CGAAACUCAA CUUCU 15 15 base pairs nucleic acid single linear 83 CUCAACUUCU GUCCC 15 15 base pairs nucleic acid single linear 84 UCAACUUCUG UCCCC 15 15 base pairs nucleic acid single linear 85 CUUCUGUCCC CAAGC 15 15 base pairs nucleic acid single linear 86 CAGCCCUACA CCUUC 15 15 base pairs nucleic acid single linear 87 GCCAUAUAGC CUUAC 15 15 base pairs nucleic acid single linear 88 CAUCCCUCAG CACCA 15 15 base pairs nucleic acid single linear 89 ACACCUUCCC AGCAU 15 15 base pairs nucleic acid single linear 90 UCCAUCUCCA GCUUC 15 15 base pairs nucleic acid single linear 91 UUUACUUUAG CGCGC 15 15 base pairs nucleic acid single linear 92 CCAGCAUCCC UCAGC 15 15 base pairs nucleic acid single linear 93 GCACCAUCAA CUUUG 15 15 base pairs nucleic acid single linear 94 AUCAACUUUG AUGAG 15 15 base pairs nucleic acid single linear 95 GAAGACUUCU CCUCC 15 15 base pairs nucleic acid single linear 96 AAGACUUCUC CUCCA 15 15 base pairs nucleic acid single linear 97 GACUUCUCCU CCAUU 15 15 base pairs nucleic acid single linear 98 UUCUCCUCCA UUGCG 15 15 base pairs nucleic acid single linear 99 CCUCCAUUGC GGACA 15 15 base pairs nucleic acid single linear 100 AUGGACUUCU CUGCU 15 15 base pairs nucleic acid single linear 101 UGGACUUCUC UGCUC 15 15 base pairs nucleic acid single linear 102 GACUUCUCUG CUCUU 15 15 base pairs nucleic acid single linear 103 UUUGAGUCAG AUCAG 15 15 base pairs nucleic acid single linear 104 GUCAGAUCAG CUCCU 15 15 base pairs nucleic acid single linear 105 AUCAGCUCCU AAGGU 15 15 base pairs nucleic acid single linear 106 AGCUCCUAAG GUGCU 15 15 base pairs nucleic acid single linear 107 CAGUGCUCCC AAGAG 15 15 base pairs nucleic acid single linear 108 CCAGGCUCCU GUUCG 15 15 base pairs nucleic acid single linear 109 AAGCCAUUAG CCAGC 15 15 base pairs nucleic acid single linear 110 UUUGAGUCAG AUCAG 15 15 base pairs nucleic acid single linear 111 AGCGAAUCCA GACCA 15 15 base pairs nucleic acid single linear 112 AACCCCUUUC ACGUU 15 15 base pairs nucleic acid single linear 113 ACCCCUUUCA CGUUC 15 15 base pairs nucleic acid single linear 114 UUCACGUUCC UAUAG 15 15 base pairs nucleic acid single linear 115 UCACGUUCCU AUAGA 15 15 base pairs nucleic acid single linear 116 CGUUCCUAUA GAGGA 15 15 base pairs nucleic acid single linear 117 UUCCUAUAGA GGAGC 15 15 base pairs nucleic acid single linear 118 GGGGACUAUG ACUUG 15 15 base pairs nucleic acid single linear 119 UGCGCCUCUG CUUCC 15 15 base pairs nucleic acid single linear 120 CUCUGCUUCC AGGUG 15 15 base pairs nucleic acid single linear 121 UCUGCUUCCA GGUGA 15 15 base pairs nucleic acid single linear 122 AAGCCAUUAG CCAGC 15 15 base pairs nucleic acid single linear 123 GGCCCCUCCU CCUGA 15 15 base pairs nucleic acid single linear 124 CCCCUGUCCU CUCAC 15 15 base pairs nucleic acid single linear 125 CUGUCCUCUC ACAUC 15 15 base pairs nucleic acid single linear 126 GUCCCUUCCU CAGCC 15 15 base pairs nucleic acid single linear 127 CCUUCCUCAG CCAUG 15 15 base pairs nucleic acid single linear 128 UCCUGCUUCC AUCUC 15 15 base pairs nucleic acid single linear 129 AUCCGAUUUU UGAUA 15 15 base pairs nucleic acid single linear 130 CCGAUUUUUG AUAAC 15 15 base pairs nucleic acid single linear 131 CGAUUUUUGA UAACC 15 15 base pairs nucleic acid single linear 132 UGGCCAUUGU GUUCC 15 15 base pairs nucleic acid single linear 133 CCGAGCUCAA GAUCU 15 15 base pairs nucleic acid single linear 134 UCAAGAUCUG CCGAG 15 15 base pairs nucleic acid single linear 135 CGGAACUCUG GGAGC 15 15 base pairs nucleic acid single linear 136 GCUGCCUCGG UGGGG 15 15 base pairs nucleic acid single linear 137 AUGAGAUCUU CUUGC 15 15 base pairs nucleic acid single linear 138 GAGAUCUUCU UGCUG 15 15 base pairs nucleic acid single linear 139 AGAUCUUCUU GCUGU 15 15 base pairs nucleic acid single linear 140 UUCUCCUCCA UUGCG 15 15 base pairs nucleic acid single linear 141 AAGACAUUGA GGUGU 15 15 base pairs nucleic acid single linear 142 GAGGUGUAUU UCACG 15 15 base pairs nucleic acid single linear 143 GGUGUAUUUC ACGGG 15 15 base pairs nucleic acid single linear 144 GUGUAUUUCA CGGGA 15 15 base pairs nucleic acid single linear 145 UGUAUUUCAC GGGAC 15 15 base pairs nucleic acid single linear 146 CGAGGCUCCU UUUCU 15 15 base pairs nucleic acid single linear 147 GAUGAGUUUU CCCCC 15 15 base pairs nucleic acid single linear 148 AUGAGUUUUC CCCCA 15 15 base pairs nucleic acid single linear 149 UGAGUUUUCC CCCAU 15 15 base pairs nucleic acid single linear 150 AUGCUGUUAC CAUCA 15 15 base pairs nucleic acid single linear 151 UGCUGUUACC AUCAG 15 15 base pairs nucleic acid single linear 152 GGCCCCUCCU CCUGA 15 15 base pairs nucleic acid single linear 153 GUCCCUUCCU CAGCC 15 15 base pairs nucleic acid single linear 154 UUACCAUCAG GGCAG 15 15 base pairs nucleic acid single linear 155 GGGAGUUUAG UCUGA 15 15 base pairs nucleic acid single linear 156 CAGCCCUACA CCUUC 15 15 base pairs nucleic acid single linear 157 CUGGCCUUAG CACCG 15 15 base pairs nucleic acid single linear 158 GGUCCCUUCC UCAGC 15 15 base pairs nucleic acid single linear 159 CCCAGCUCCU GCCCC 15 15 base pairs nucleic acid single linear 160 CCAGCCUCCA GGCUC 15 15 base pairs nucleic acid single linear 161 CCCAGCUCCU GCCCC 15 15 base pairs nucleic acid single linear 162 CCAUGGUCCC UUCCU 15 15 base pairs nucleic acid single linear 163 GUGGGCUCAG CUGCG 15 15 base pairs nucleic acid single linear 164 AUGAGUUUUC CCCCA 15 15 base pairs nucleic acid single linear 165 CUCCUGUUCG AGUCU 15 15 base pairs nucleic acid single linear 166 CCCCAGUUCU AACCC 15 15 base pairs nucleic acid single linear 167 CAGUUCUAAC CCCGG 15 15 base pairs nucleic acid single linear 168 GGGUCCUCCC CAGUC 15 15 base pairs nucleic acid single linear 169 CUUUUCUCAA GCUGA 15 15 base pairs nucleic acid single linear 170 ACGCUGUCGG AAGCC 15 15 base pairs nucleic acid single linear 171 CUGCAGUUUG AUGCU 15 15 base pairs nucleic acid single linear 172 UGCAGUUUGA UGCUG 15 15 base pairs nucleic acid single linear 173 GGGGCCUUGC UUGGC 15 15 base pairs nucleic acid single linear 174 CCUUGCUUGG CAACA 15 15 base pairs nucleic acid single linear 175 GGAGUGUUCA CAGAC 15 15 base pairs nucleic acid single linear 176 GAGUGUUCAC AGACC 15 15 base pairs nucleic acid single linear 177 CUGGCAUCUG UGGAC 15 15 base pairs nucleic acid single linear 178 CUUCGGUAGG GAACU 15 15 base pairs nucleic acid single linear 179 GACAACUCAG AGUUU 15 15 base pairs nucleic acid single linear 180 UCAGAGUUUC AGCAG 15 15 base pairs nucleic acid single linear 181 CAGAGUUUCA GCAGC 15 15 base pairs nucleic acid single linear 182 AGAGUUUCAG CAGCU 15 15 base pairs nucleic acid single linear 183 GGUGCAUCCC UGUGU 15 15 base pairs nucleic acid single linear 184 AUGGAGUACC CUGAA 15 15 base pairs nucleic acid single linear 185 UGAAGCUAUA ACUCG 15 15 base pairs nucleic acid single linear 186 AAGCUAUAAC UCGCC 15 15 base pairs nucleic acid single linear 187 UAUAACUCGC CUGGU 15 15 base pairs nucleic acid single linear 188 CUCUCCUAGA GAGGG 15 15 base pairs nucleic acid single linear 189 CCCAGCUCCU GCCCC 15 15 base pairs nucleic acid single linear 190 UCCUGCUUCG GUAGG 15 15 base pairs nucleic acid single linear 191 CGGGGCUUCC CAAUG 15 15 base pairs nucleic acid single linear 192 CUGACCUCUG CCCAG 15 15 base pairs nucleic acid single linear 193 CUCUGCUUCC AGGUG 15 15 base pairs nucleic acid single linear 194 UCUGCUUCCA GGUGA 15 15 base pairs nucleic acid single linear 195 CUCGCUUUCG GAGGU 15 15 base pairs nucleic acid single linear 196 AAUGGCUCGU CUGUA 15 15 base pairs nucleic acid single linear 197 GGCUCGUCUG UAGUG 15 15 base pairs nucleic acid single linear 198 CGUCUGUAGU GCACG 15 15 base pairs nucleic acid single linear 199 GAACUGUUCC CCCUC 15 15 base pairs nucleic acid single linear 200 AACUGUUCCC CCUCA 15 15 base pairs nucleic acid single linear 201 UCCCCCUCAU CUUCC 15 15 base pairs nucleic acid single linear 202 CCCUCAUCUU CCCGG 15 15 base pairs nucleic acid single linear 203 CUCAUCUUCC CGGCA 15 15 base pairs nucleic acid single linear 204 UCAUCUUCCC GGCAG 15 15 base pairs nucleic acid single linear 205 CAGGCCUCUG GCCCC 15 15 base pairs nucleic acid single linear 206 GGCCCCUAUG UGGAG 15 15 base pairs nucleic acid single linear 207 UGGAGAUCAU UGAGC 15 15 base pairs nucleic acid single linear 208 AGAUCAUUGA GCAGC 15 15 base pairs nucleic acid single linear 209 AUGCGCUUCC GCUAC 15 15 base pairs nucleic acid single linear 210 UGCGCUUCCG CUACA 15 15 base pairs nucleic acid single linear 211 UUCCGCUACA AGUGC 15 15 base pairs nucleic acid single linear 212 GGGCGCUCCG CGGGC 15 15 base pairs nucleic acid single linear 213 GCAGCAUCCC AGGCG 15 15 base pairs nucleic acid single linear 214 CACAGAUACC ACCAA 15 15 base pairs nucleic acid single linear 215 CCACCAUCAA GAUCA 15 15 base pairs nucleic acid single linear 216 UCAAGAUCAA UGGCU 15 15 base pairs nucleic acid single linear 217 AAUGGCUACA CAGGA 15 15 base pairs nucleic acid single linear 218 UGCGCAUCUC CCUGG 15 15 base pairs nucleic acid single linear 219 CGCAUCUCCC UGGUC 15 15 base pairs nucleic acid single linear 220 CCCUGGUCAC CAAGG 15 15 base pairs nucleic acid single linear 221 GGACCCUCCU CACCG 15 15 base pairs nucleic acid single linear 222 CCCUCCUCAC CGGCC 15 15 base pairs nucleic acid single linear 223 CCGGCCUCAC CCCCA 15 15 base pairs nucleic acid single linear 224 ACGAGCUUGU AGGAA 15 15 base pairs nucleic acid single linear 225 AGCUUGUAGG AAAGG 15 15 base pairs nucleic acid single linear 226 GAUGGCUUCU AUGAG 15 15 base pairs nucleic acid single linear 227 AUGGCUUCUA UGAGG 15 15 base pairs nucleic acid single linear 228 GGCUUCUAUG AGGCU 15 15 base pairs nucleic acid single linear 229 CUGAGCUCUG CCCGG 15 15 base pairs nucleic acid single linear 230 GCUGCAUCCA CAGUU 15 15 base pairs nucleic acid single linear 231 CCACAGUUUC CAGAA 15 15 base pairs nucleic acid single linear 232 CACAGUUUCC AGAAC 15 15 base pairs nucleic acid single linear 233 ACAGUUUCCA GAACC 15 15 base pairs nucleic acid single linear 234 UGGGAAUCCA GUGUG 15 15 base pairs nucleic acid single linear 235 GGCUCCUUUU CGCAA 15 15 base pairs nucleic acid single linear 236 GCUCCUUUUC GCAAG 15 15 base pairs nucleic acid single linear 237 CUCCUUUUCG CAAGC 15 15 base pairs nucleic acid single linear 238 UCCUUUUCGC AAGCU 15 15 base pairs nucleic acid single linear 239 UGGCCAUUGU GUUCC 15 15 base pairs nucleic acid single linear 240 AUUGUGUUCC GGACC 15 15 base pairs nucleic acid single linear 241 UUGUGUUCCG GACCC 15 15 base pairs nucleic acid single linear 242 GACCCCUCCC UACGC 15 15 base pairs nucleic acid single linear 243 CCUCCCUACG CAGAC 15 15 base pairs nucleic acid single linear 244 GCAGGCUCCU GUGCG 15 15 base pairs nucleic acid single linear 245 UGCGUGUCUC CAUGC 15 15 base pairs nucleic acid single linear 246 CGUGUCUCCA UGCAG 15 15 base pairs nucleic acid single linear 247 GCGGCCUUCC GACCG 15 15 base pairs nucleic acid single linear 248 CGGCCUUCCG ACCGG 15 15 base pairs nucleic acid single linear 249 GGGAGCUCAG UGAGC 15 15 base pairs nucleic acid single linear 250 AUGGAAUUCC AGUAC 15 15 base pairs nucleic acid single linear 251 UGGAAUUCCA GUACC 15 15 base pairs nucleic acid single linear 252 UUCCAGUACC UGCCA 15 15 base pairs nucleic acid single linear 253 GCCAGAUACA GACGA 15 15 base pairs nucleic acid single linear 254 AGACGAUCGU CACCG 15 15 base pairs nucleic acid single linear 255 CGAUCGUCAC CGGAU 15 15 base pairs nucleic acid single linear 256 ACCGGAUUGA GGAGA 15 15 base pairs nucleic acid single linear 257 GAAACGUAAA AGGAC 15 15 base pairs nucleic acid single linear 258 AGGACAUAUG AGACC 15 15 base pairs nucleic acid single linear 259 GAGACCUUCA AGAGC 15 15 base pairs nucleic acid single linear 260 AGACCUUCAA GAGCA 15 15 base pairs nucleic acid single linear 261 AGAGCAUCAU GAAGA 15 15 base pairs nucleic acid single linear 262 GAAGAGUCCU UUCAG 15 15 base pairs nucleic acid single linear 263 GAGUCCUUUC AGCGG 15 15 base pairs nucleic acid single linear 264 AGUCCUUUCA GCGGA 15 15 base pairs nucleic acid single linear 265 GUCCUUUCAG CGGAC 15 15 base pairs nucleic acid single linear 266 CCGGCCUCCA CCUCG 15 15 base pairs nucleic acid single linear 267 UCCACCUCGA CGCAU 15 15 base pairs nucleic acid single linear 268 GACGCAUUGC UGUGC 15 15 base pairs nucleic acid single linear 269 UGUGCCUUCC CGCAG 15 15 base pairs nucleic acid single linear 270 GUGCCUUCCC GCAGC 15 15 base pairs nucleic acid single linear 271 CGCAGCUCAG CUUCU 15 15 base pairs nucleic acid single linear 272 CUCAGCUUCU GUCCC 15 15 base pairs nucleic acid single linear 273 UCAGCUUCUG UCCCC 15 15 base pairs nucleic acid single linear 274 CUUCUGUCCC CAAGC 15 15 base pairs nucleic acid single linear 275 CAGCCCUAUC CCUUU 15 15 base pairs nucleic acid single linear 276 GCCCUAUCCC UUUAC 15 15 base pairs nucleic acid single linear 277 UAUCCCUUUA CGUCA 15 15 base pairs nucleic acid single linear 278 AUCCCUUUAC GUCAU 15 15 base pairs nucleic acid single linear 279 UCCCUUUACG UCAUC 15 15 base pairs nucleic acid single linear 280 UUUACGUCAU CCCUG 15 15 base pairs nucleic acid single linear 281 ACGUCAUCCC UGAGC 15 15 base pairs nucleic acid single linear 282 GCACCAUCAA CUAUG 15 15 base pairs nucleic acid single linear 283 AUCAACUAUG AUGAG 15 15 base pairs nucleic acid single linear 284 GAAGACUUCU CCUCC 15 15 base pairs nucleic acid single linear 285 AAGACUUCUC CUCCA 15 15 base pairs nucleic acid single linear 286 GACUUCUCCU CCAUU 15 15 base pairs nucleic acid single linear 287 UUCUCCUCCA UUGCG 15 15 base pairs nucleic acid single linear 288 CCUCCAUUGC GGACA 15 15 base pairs nucleic acid single linear 289 AUGGACUUCU CAGCC 15 15 base pairs nucleic acid single linear 290 UGGACUUCUC AGCCC 15 15 base pairs nucleic acid single linear 291 GACUUCUCAG CCCUG 15 15 base pairs nucleic acid single linear 292 GCUGAGUCAG AUCAG 15 15 base pairs nucleic acid single linear 293 GUCAGAUCAG CUCCU 15 15 base pairs nucleic acid single linear 294 AUCAGCUCCU AAGGG 15 15 base pairs nucleic acid single linear 295 AGCUCCUAAG GGGGU 15 15 base pairs nucleic acid single linear 296 CUGCCCUCCC CAGAG 15 15 base pairs nucleic acid single linear 297 GCAGGCUAUC AGUCA 15 15 base pairs nucleic acid single linear 298 AGGCUAUCAG UCAGC 15 15 base pairs nucleic acid single linear 299 UAUCAGUCAG CGCAU 15 15 base pairs nucleic acid single linear 300 AGCGCAUCCA GACCA 15 15 base pairs nucleic acid single linear 301 AACCCCUUCC AAGUU 15 15 base pairs nucleic acid single linear 302 ACCCCUUCCA AGUUC 15 15 base pairs nucleic acid single linear 303 UCCAAGUUCC UAUAG 15 15 base pairs nucleic acid single linear 304 CCAAGUUCCU AUAGA 15 15 base pairs nucleic acid single linear 305 AGUUCCUAUA GAAGA 15 15 base pairs nucleic acid single linear 306 UUCCUAUAGA AGAGC 15 15 base pairs nucleic acid single linear 307 GGGGACUACG ACCUG 15 15 base pairs nucleic acid single linear 308 UGCGGCUCUG CUUCC 15 15 base pairs nucleic acid single linear 309 CUCUGCUUCC AGGUG 15 15 base pairs nucleic acid single linear 310 UCUGCUUCCA GGUGA 15 15 base pairs nucleic acid single linear 311 GACCCAUCAG GCAGG 15 15 base pairs nucleic acid single linear 312 GGCCCCUCCG CCUGC 15 15 base pairs nucleic acid single linear 313 CGCCUGUCCU UCCUC 15 15 base pairs nucleic acid single linear 314 CUGUCCUUCC UCAUC 15 15 base pairs nucleic acid single linear 315 UGUCCUUCCU CAUCC 15 15 base pairs nucleic acid single linear 316 CCUUCCUCAU CCCAU 15 15 base pairs nucleic acid single linear 317 UCCUCAUCCC AUCUU 15 15 base pairs nucleic acid single linear 318 AUCCCAUCUU UGACA 15 15 base pairs nucleic acid single linear 319 CCCAUCUUUG ACAAU 15 15 base pairs nucleic acid single linear 320 CCAUCUUUGA CAAUC 15 15 base pairs nucleic acid single linear 321 UGACAAUCGU GCCCC 15 15 base pairs nucleic acid single linear 322 CCGAGCUCAA GAUCU 15 15 base pairs nucleic acid single linear 323 UCAAGAUCUG CCGAG 15 15 base pairs nucleic acid single linear 324 CGAAACUCUG GCAGC 15 15 base pairs nucleic acid single linear 325 GCUGCCUCGG UGGGG 15 15 base pairs nucleic acid single linear 326 AUGAGAUCUU CCUAC 15 15 base pairs nucleic acid single linear 327 GAGAUCUUCC UACUG 15 15 base pairs nucleic acid single linear 328 AGAUCUUCCU ACUGU 15 15 base pairs nucleic acid single linear 329 UCUUCCUACU GUGUG 15 15 base pairs nucleic acid single linear 330 AGGACAUUGA GGUGU 15 15 base pairs nucleic acid single linear 331 GAGGUGUAUU UCACG 15 15 base pairs nucleic acid single linear 332 GGUGUAUUUC ACGGG 15 15 base pairs nucleic acid single linear 333 GUGUAUUUCA CGGGA 15 15 base pairs nucleic acid single linear 334 UGUAUUUCAC GGGAC 15 15 base pairs nucleic acid single linear 335 CGAGGCUCCU UUUCG 15 15 base pairs nucleic acid single linear 336 GAUGAGUUUC CCACC 15 15 base pairs nucleic acid single linear 337 AUGAGUUUCC CACCA 15 15 base pairs nucleic acid single linear 338 UGAGUUUCCC ACCAU 15 15 base pairs nucleic acid single linear 339 AUGGUGUUUC CUUCU 15 15 base pairs nucleic acid single linear 340 UGGUGUUUCC UUCUG 15 15 base pairs nucleic acid single linear 341 GGUGUUUCCU UCUGG 15 15 base pairs nucleic acid single linear 342 GUUUCCUUCU GGGCA 15 15 base pairs nucleic acid single linear 343 UUUCCUUCUG GGCAG 15 15 base pairs nucleic acid single linear 344 GGCAGAUCAG CCAGG 15 15 base pairs nucleic acid single linear 345 CAGGCCUCGG CCUUG 15 15 base pairs nucleic acid single linear 346 UCGGCCUUGG CCCCG 15 15 base pairs nucleic acid single linear 347 GGCCCCUCCC CAAGU 15 15 base pairs nucleic acid single linear 348 CCCAAGUCCU GCCCC 15 15 base pairs nucleic acid single linear 349 CCAGGCUCCA GCCCC 15 15 base pairs nucleic acid single linear 350 CCCUGCUCCA GCCAU 15 15 base pairs nucleic acid single linear 351 CCAUGGUAUC AGCUC 15 15 base pairs nucleic acid single linear 352 AUGGUAUCAG CUCUG 15 15 base pairs nucleic acid single linear 353 AUCAGCUCUG GCCCA 15 15 base pairs nucleic acid single linear 354 CCCCUGUCCC AGUCC 15 15 base pairs nucleic acid single linear 355 UCCCAGUCCU AGCCC 15 15 base pairs nucleic acid single linear 356 CAGUCCUAGC CCCAG 15 15 base pairs nucleic acid single linear 357 AGGCCCUCCU CAGGC 15 15 base pairs nucleic acid single linear 358 CCCUCCUCAG GCUGU 15 15 base pairs nucleic acid single linear 359 ACGCUGUCAG AGGCC 15 15 base pairs nucleic acid single linear 360 CUGCAGUUUG AUGAU 15 15 base pairs nucleic acid single linear 361 UGCAGUUUGA UGAUG 15 15 base pairs nucleic acid single linear 362 GGGGCCUUGC UUGGC 15 15 base pairs nucleic acid single linear 363 CCUUGCUUGG CAACA 15 15 base pairs nucleic acid single linear 364 GCUGUGUUCA CAGAC 15 15 base pairs nucleic acid single linear 365 CUGUGUUCAC AGACC 15 15 base pairs nucleic acid single linear 366 CUGGCAUCCG UCGAC 15 15 base pairs nucleic acid single linear 367 CAUCCGUCGA CAACU 15 15 base pairs nucleic acid single linear 368 GACAACUCCG AGUUU 15 15 base pairs nucleic acid single linear 369 UCCGAGUUUC AGCAG 15 15 base pairs nucleic acid single linear 370 CCGAGUUUCA GCAGC 15 15 base pairs nucleic acid single linear 371 CGAGUUUCAG CAGCU 15 15 base pairs nucleic acid single linear 372 AGGGCAUACC UGUGG 15 15 base pairs nucleic acid single linear 373 AUGGAGUACC CUGAG 15 15 base pairs nucleic acid single linear 374 UGAGGCUAUA ACUCG 15 15 base pairs nucleic acid single linear 375 AGGCUAUAAC UCGCC 15 15 base pairs nucleic acid single linear 376 UAUAACUCGC CUAGU 15 15 base pairs nucleic acid single linear 377 CUCGCCUAGU GACAG 15 15 base pairs nucleic acid single linear 378 CCCAGCUCCU GCUCC 15 15 base pairs nucleic acid single linear 379 UCCUGCUCCA CUGGG 15 15 base pairs nucleic acid single linear 380 CGGGGCUCCC CAAUG 15 15 base pairs nucleic acid single linear 381 AUGGCCUCCU UUCAG 15 15 base pairs nucleic acid single linear 382 GCCUCCUUUC AGGAG 15 15 base pairs nucleic acid single linear 383 CCUCCUUUCA GGAGA 15 15 base pairs nucleic acid single linear 384 CUCCUUUCAG GAGAU 15 36 base pairs nucleic acid single linear 385 UCCUGUGCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acid single linear 386 CACCACGCUG AUGAGGCCGA AAGGCCGAAA GGAGCU 36 36 base pairs nucleic acid single linear 387 UGUCCGCCUG AUGAGGCCGA AAGGCCGAAA UGGAGG 36 36 base pairs nucleic acid single linear 388 GAGGGGACUG AUGAGGCCGA AAGGCCGAAA CAGAUC 36 36 base pairs nucleic acid single linear 389 UGAGGGGCUG AUGAGGCCGA AAGGCCGAAA ACAGAU 36 36 base pairs nucleic acid single linear 390 GAAAGAUCUG AUGAGGCCGA AAGGCCGAAA GGGGAA 36 36 base pairs nucleic acid single linear 391 AGGGAAACUG AUGAGGCCGA AAGGCCGAAA UGAGGG 36 36 base pairs nucleic acid single linear 392 UGAGGGACUG AUGAGGCCGA AAGGCCGAAA GAUGAG 36 36 base pairs nucleic acid single linear 393 CUGAGGGCUG AUGAGGCCGA AAGGCCGAAA AGAUGA 36 36 base pairs nucleic acid single linear 394 AGGCCCACUG AUGAGGCCGA AAGGCCGAAA AGCCUG 36 36 base pairs nucleic acid single linear 395 CUCCACACUG AUGAGGCCGA AAGGCCGAAA AGGCCC 36 36 base pairs nucleic acid single linear 396 GUUCGAUCUG AUGAGGCCGA AAGGCCGAAA UCUCCA 36 36 base pairs nucleic acid single linear 397 GCUGUUCCUG AUGAGGCCGA AAGGCCGAAA UGAUCU 36 36 base pairs nucleic acid single linear 398 AUAGCGGCUG AUGAGGCCGA AAGGCCGAAA UCGCAU 36 36 base pairs nucleic acid single linear 399 UAUAGCGCUG AUGAGGCCGA AAGGCCGAAA AUCGCA 36 36 base pairs nucleic acid single linear 400 GCAUUUACUG AUGAGGCCGA AAGGCCGAAA GCGGAA 36 36 base pairs nucleic acid single linear 401 GCCCGCUCUG AUGAGGCCGA AAGGCCGAAA GCGCCC 36 36 base pairs nucleic acid single linear 402 CGCCAGGCUG AUGAGGCCGA AAGGCCGAAA UACUGC 36 36 base pairs nucleic acid single linear 403 UUGGUGGCUG AUGAGGCCGA AAGGCCGAAA UCUGUG 36 36 base pairs nucleic acid single linear 404 UGAUCUUCUG AUGAGGCCGA AAGGCCGAAA UGGUGG 36 36 base pairs nucleic acid single linear 405 AGCCAUUCUG AUGAGGCCGA AAGGCCGAAA UCUUGA 36 36 base pairs nucleic acid single linear 406 UCCUGUGCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acid single linear 407 CCAGGGACUG AUGAGGCCGA AAGGCCGAAA UUCGAA 36 36 base pairs nucleic acid single linear 408 GACCAGGCUG AUGAGGCCGA AAGGCCGAAA GAUUCG 36 36 base pairs nucleic acid single linear 409 CCUUGGUCUG AUGAGGCCGA AAGGCCGAAA CCAGGG 36 36 base pairs nucleic acid single linear 410 UCAGGAGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear 411 GGCCGGUCUG AUGAGGCCGA AAGGCCGAAA GGUGGA 36 36 base pairs nucleic acid single linear 412 UGUGGAUCUG AUGAGGCCGA AAGGCCGAAA GGCCGG 36 36 base pairs nucleic acid single linear 413 UCCCCACCUG AUGAGGCCGA AAGGCCGAAA GUUCAU 36 36 base pairs nucleic acid single linear 414 GCUGUUCCUG AUGAGGCCGA AAGGCCGAAA UGAUCU 36 36 base pairs nucleic acid single linear 415 CUCAUAGCUG AUGAGGCCGA AAGGCCGAAA GCCAUC 36 36 base pairs nucleic acid single linear 416 CUCCGGACUG AUGAGGCCGA AAGGCCGAAA GACCAU 36 36 base pairs nucleic acid single linear 417 AGCCUCACUG AUGAGGCCGA AAGGCCGAAA GUAGCC 36 36 base pairs nucleic acid single linear 418 CUGGGCACUG AUGAGGCCGA AAGGCCGAAA GGUCAG 36 36 base pairs nucleic acid single linear 419 AGCUAUGCUG AUGAGGCCGA AAGGCCGAAA UACUGC 36 36 base pairs nucleic acid single linear 420 CUAUGGACUG AUGAGGCCGA AAGGCCGAAA CUGCGG 36 36 base pairs nucleic acid single linear 421 GUUCUGGCUG AUGAGGCCGA AAGGCCGAAA GCUAUG 36 36 base pairs nucleic acid single linear 422 GGUUCUGCUG AUGAGGCCGA AAGGCCGAAA AGCUAU 36 36 base pairs nucleic acid single linear 423 CACACUGCUG AUGAGGCCGA AAGGCCGAAA UCCCCA 36 36 base pairs nucleic acid single linear 424 CGAACAGCUG AUGAGGCCGA AAGGCCGAAA GCCUGG 36 36 base pairs nucleic acid single linear 425 GCUGGCUCUG AUGAGGCCGA AAGGCCGAAA UGGCUU 36 36 base pairs nucleic acid single linear 426 CUGAUCUCUG AUGAGGCCGA AAGGCCGAAA CUCAAA 36 36 base pairs nucleic acid single linear 427 UGGUCUGCUG AUGAGGCCGA AAGGCCGAAA UUCGCU 36 36 base pairs nucleic acid single linear 428 AACGUGACUG AUGAGGCCGA AAGGCCGAAA GGGGUU 36 36 base pairs nucleic acid single linear 429 GAACGUGCUG AUGAGGCCGA AAGGCCGAAA AGGGGU 36 36 base pairs nucleic acid single linear 430 CUAUAGGCUG AUGAGGCCGA AAGGCCGAAA CGUGAA 36 36 base pairs nucleic acid single linear 431 UCUAUAGCUG AUGAGGCCGA AAGGCCGAAA ACGUGA 36 36 base pairs nucleic acid single linear 432 UCCUCUACUG AUGAGGCCGA AAGGCCGAAA GGAACG 36 36 base pairs nucleic acid single linear 433 GCUCCUCCUG AUGAGGCCGA AAGGCCGAAA UAGGAA 36 36 base pairs nucleic acid single linear 434 CAAGUCACUG AUGAGGCCGA AAGGCCGAAA GUCCCC 36 36 base pairs nucleic acid single linear 435 GGAAGCACUG AUGAGGCCGA AAGGCCGAAA GGCGCA 36 36 base pairs nucleic acid single linear 436 CACCUGGCUG AUGAGGCCGA AAGGCCGAAA GCAGAG 36 36 base pairs nucleic acid single linear 437 UCACCUGCUG AUGAGGCCGA AAGGCCGAAA AGCAGA 36 36 base pairs nucleic acid single linear 438 GCUGGCUCUG AUGAGGCCGA AAGGCCGAAA UGGCUU 36 36 base pairs nucleic acid single linear 439 UCAGGAGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear 440 GUGAGAGCUG AUGAGGCCGA AAGGCCGAAA CAGGGG 36 36 base pairs nucleic acid single linear 441 GAUGUGACUG AUGAGGCCGA AAGGCCGAAA GGACAG 36 36 base pairs nucleic acid single linear 442 GGCUGAGCUG AUGAGGCCGA AAGGCCGAAA AGGGAC 36 36 base pairs nucleic acid single linear 443 CAUGGCUCUG AUGAGGCCGA AAGGCCGAAA GGAAGG 36 36 base pairs nucleic acid single linear 444 GAGAUGGCUG AUGAGGCCGA AAGGCCGAAA GCAGGA 36 36 base pairs nucleic acid single linear 445 UAUCAAACUG AUGAGGCCGA AAGGCCGAAA UCGGAU 36 36 base pairs nucleic acid single linear 446 GUUAUCACUG AUGAGGCCGA AAGGCCGAAA AAUCGG 36 36 base pairs nucleic acid single linear 447 GGUUAUCCUG AUGAGGCCGA AAGGCCGAAA AAAUCG 36 36 base pairs nucleic acid single linear 448 GGAACACCUG AUGAGGCCGA AAGGCCGAAA UGGCCA 36 36 base pairs nucleic acid single linear 449 AGAUCUUCUG AUGAGGCCGA AAGGCCGAAA GCUCGG 36 36 base pairs nucleic acid single linear 450 CUCGGCACUG AUGAGGCCGA AAGGCCGAAA UCUUGA 36 36 base pairs nucleic acid single linear 451 GCUCCCACUG AUGAGGCCGA AAGGCCGAAA GUUCCG 36 36 base pairs nucleic acid single linear 452 CCCCACCCUG AUGAGGCCGA AAGGCCGAAA GGCAGC 36 36 base pairs nucleic acid single linear 453 GCAAGAACUG AUGAGGCCGA AAGGCCGAAA UCUCAU 36 36 base pairs nucleic acid single linear 454 CAGCAAGCUG AUGAGGCCGA AAGGCCGAAA GAUCUC 36 36 base pairs nucleic acid single linear 455 ACAGCAACUG AUGAGGCCGA AAGGCCGAAA AGAUCU 36 36 base pairs nucleic acid single linear 456 CGCAAUGCUG AUGAGGCCGA AAGGCCGAAA GGAGAA 36 36 base pairs nucleic acid single linear 457 ACACCUCCUG AUGAGGCCGA AAGGCCGAAA UGUCUU 36 36 base pairs nucleic acid single linear 458 CGUGAAACUG AUGAGGCCGA AAGGCCGAAA CACCUC 36 36 base pairs nucleic acid single linear 459 CCCGUGACUG AUGAGGCCGA AAGGCCGAAA UACACC 36 36 base pairs nucleic acid single linear 460 UCCCGUGCUG AUGAGGCCGA AAGGCCGAAA AUACAC 36 36 base pairs nucleic acid single linear 461 GUCCCGUCUG AUGAGGCCGA AAGGCCGAAA AAUACA 36 36 base pairs nucleic acid single linear 462 AGAAAAGCUG AUGAGGCCGA AAGGCCGAAA GCCUCG 36 36 base pairs nucleic acid single linear 463 UUGAGAACUG AUGAGGCCGA AAGGCCGAAA GGAGCC 36 36 base pairs nucleic acid single linear 464 CUUGAGACUG AUGAGGCCGA AAGGCCGAAA AGGAGC 36 36 base pairs nucleic acid single linear 465 GCUUGAGCUG AUGAGGCCGA AAGGCCGAAA AAGGAG 36 36 base pairs nucleic acid single linear 466 AGCUUGACUG AUGAGGCCGA AAGGCCGAAA AAAGGA 36 36 base pairs nucleic acid single linear 467 GGAACACCUG AUGAGGCCGA AAGGCCGAAA UGGCCA 36 36 base pairs nucleic acid single linear 468 AGUCCGGCUG AUGAGGCCGA AAGGCCGAAA CACAAU 36 36 base pairs nucleic acid single linear 469 GAGUCCGCUG AUGAGGCCGA AAGGCCGAAA ACACAA 36 36 base pairs nucleic acid single linear 470 GCGUACGCUG AUGAGGCCGA AAGGCCGAAA GGAGUC 36 36 base pairs nucleic acid single linear 471 GUCGGCGCUG AUGAGGCCGA AAGGCCGAAA CGGAGG 36 36 base pairs nucleic acid single linear 472 CGAACAGCUG AUGAGGCCGA AAGGCCGAAA GCCUGG 36 36 base pairs nucleic acid single linear 473 GCAUGGACUG AUGAGGCCGA AAGGCCGAAA CUCGAA 36 36 base pairs nucleic acid single linear 474 CUGCAUGCUG AUGAGGCCGA AAGGCCGAAA GACUCG 36 36 base pairs nucleic acid single linear 475 CGAUCAGCUG AUGAGGCCGA AAGGCCGAAA GGCCGC 36 36 base pairs nucleic acid single linear 476 GCGAUCACUG AUGAGGCCGA AAGGCCGAAA AGGCCG 36 36 base pairs nucleic acid single linear 477 GCUCACUCUG AUGAGGCCGA AAGGCCGAAA GCUCGC 36 36 base pairs nucleic acid single linear 478 GUACUGGCUG AUGAGGCCGA AAGGCCGAAA CUCCAU 36 36 base pairs nucleic acid single linear 479 AGUACUGCUG AUGAGGCCGA AAGGCCGAAA ACUCCA 36 36 base pairs nucleic acid single linear 480 UGGCAAGCUG AUGAGGCCGA AAGGCCGAAA CUGGAA 36 36 base pairs nucleic acid single linear 481 UCAUGUGCUG AUGAGGCCGA AAGGCCGAAA UGAGGC 36 36 base pairs nucleic acid single linear 482 CGGUGGCCUG AUGAGGCCGA AAGGCCGAAA UCAUCU 36 36 base pairs nucleic acid single linear 483 GUCUGGCCUG AUGAGGCCGA AAGGCCGAAA GUACUG 36 36 base pairs nucleic acid single linear 484 UCUCUUCCUG AUGAGGCCGA AAGGCCGAAA UCCGGU 36 36 base pairs nucleic acid single linear 485 ACUCUUGCUG AUGAGGCCGA AAGGCCGAAA GGUCUC 36 36 base pairs nucleic acid single linear 486 GGUCUCACUG AUGAGGCCGA AAGGCCGAAA GGUCCU 36 36 base pairs nucleic acid single linear 487 ACUCUUGCUG AUGAGGCCGA AAGGCCGAAA GGUCUC 36 36 base pairs nucleic acid single linear 488 UACUCUUCUG AUGAGGCCGA AAGGCCGAAA AGGUCU 36 36 base pairs nucleic acid single linear 489 UCUUCAUCUG AUGAGGCCGA AAGGCCGAAA UACUCU 36 36 base pairs nucleic acid single linear 490 UUGAAAGCUG AUGAGGCCGA AAGGCCGAAA CUCUUC 36 36 base pairs nucleic acid single linear 491 CCAUUGACUG AUGAGGCCGA AAGGCCGAAA GGACUC 36 36 base pairs nucleic acid single linear 492 UCCAUUGCUG AUGAGGCCGA AAGGCCGAAA AGGACU 36 36 base pairs nucleic acid single linear 493 GUCCAUUCUG AUGAGGCCGA AAGGCCGAAA AAGGAC 36 36 base pairs nucleic acid single linear 494 CGGGUUGCUG AUGAGGCCGA AAGGCCGAAA GGCCGG 36 36 base pairs nucleic acid single linear 495 UUGGAUCCUG AUGAGGCCGA AAGGCCGAAA GGUGUA 36 36 base pairs nucleic acid single linear 496 GCACAGCCUG AUGAGGCCGA AAGGCCGAAA UACGCC 36 36 base pairs nucleic acid single linear 497 UUUCGGGCUG AUGAGGCCGA AAGGCCGAAA GGCACA 36 36 base pairs nucleic acid single linear 498 ACUUCGGCUG AUGAGGCCGA AAGGCCGAAA AGGCUU 36 36 base pairs nucleic acid single linear 499 AGAAGUUCUG AUGAGGCCGA AAGGCCGAAA GUUUCG 36 36 base pairs nucleic acid single linear 500 GGGACAGCUG AUGAGGCCGA AAGGCCGAAA GUUGAG 36 36 base pairs nucleic acid single linear 501 GGGGACACUG AUGAGGCCGA AAGGCCGAAA AGUUGA 36 36 base pairs nucleic acid single linear 502 GCUUGGGCUG AUGAGGCCGA AAGGCCGAAA CAGAAG 36 36 base pairs nucleic acid single linear 503 GAAGGUGCUG AUGAGGCCGA AAGGCCGAAA GGGCUG 36 36 base pairs nucleic acid single linear 504 GUAAGGCCUG AUGAGGCCGA AAGGCCGAAA UAUGGC 36 36 base pairs nucleic acid single linear 505 UGGUGCUCUG AUGAGGCCGA AAGGCCGAAA GGGAUG 36 36 base pairs nucleic acid single linear 506 AUGCUGGCUG AUGAGGCCGA AAGGCCGAAA AGGUGU 36 36 base pairs nucleic acid single linear 507 GAAGCUGCUG AUGAGGCCGA AAGGCCGAAA GAUGGA 36 36 base pairs nucleic acid single linear 508 GCGCGCUCUG AUGAGGCCGA AAGGCCGAAA AGUAAA 36 36 base pairs nucleic acid single linear 509 GCUGAGGCUG AUGAGGCCGA AAGGCCGAAA UGCUGG 36 36 base pairs nucleic acid single linear 510 CAAAGUUCUG AUGAGGCCGA AAGGCCGAAA UGGUGC 36 36 base pairs nucleic acid single linear 511 CUCAUCACUG AUGAGGCCGA AAGGCCGAAA GUUGAU 36 36 base pairs nucleic acid single linear 512 GGGGGAACUG AUGAGGCCGA AAGGCCGAAA CUCAUC 36 36 base pairs nucleic acid single linear 513 UGGGGGACUG AUGAGGCCGA AAGGCCGAAA ACUCAU 36 36 base pairs nucleic acid single linear 514 AUGGGGGCUG AUGAGGCCGA AAGGCCGAAA AACUCA 36 36 base pairs nucleic acid single linear 515 UGAUGGUCUG AUGAGGCCGA AAGGCCGAAA CAGCAU 36 36 base pairs nucleic acid single linear 516 CUGAUGGCUG AUGAGGCCGA AAGGCCGAAA ACAGCA 36 36 base pairs nucleic acid single linear 517 UCAGGAGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear 518 GGCUGAGCUG AUGAGGCCGA AAGGCCGAAA AGGGAC 36 36 base pairs nucleic acid single linear 519 CUGCCCUCUG AUGAGGCCGA AAGGCCGAAA UGGUAA 36 36 base pairs nucleic acid single linear 520 UCAGACUCUG AUGAGGCCGA AAGGCCGAAA ACUCCC 36 36 base pairs nucleic acid single linear 521 GAAGGUGCUG AUGAGGCCGA AAGGCCGAAA GGGCUG 36 36 base pairs nucleic acid single linear 522 CGGUGCUCUG AUGAGGCCGA AAGGCCGAAA GGCCAG 36 36 base pairs nucleic acid single linear 523 GCUGAGGCUG AUGAGGCCGA AAGGCCGAAA GGGACC 36 36 base pairs nucleic acid single linear 524 GGGGCAGCUG AUGAGGCCGA AAGGCCGAAA GCUGGG 36 36 base pairs nucleic acid single linear 525 GAGCCUGCUG AUGAGGCCGA AAGGCCGAAA GGCUGG 36 36 base pairs nucleic acid single linear 526 GGGGCAGCUG AUGAGGCCGA AAGGCCGAAA GCUGGG 36 36 base pairs nucleic acid single linear 527 AGGAAGGCUG AUGAGGCCGA AAGGCCGAAA CCAUGG 36 36 base pairs nucleic acid single linear 528 CGCAGCUCUG AUGAGGCCGA AAGGCCGAAA GCCCAC 36 36 base pairs nucleic acid single linear 529 UGGGGGACUG AUGAGGCCGA AAGGCCGAAA ACUCAU 36 36 base pairs nucleic acid single linear 530 AGACUCGCUG AUGAGGCCGA AAGGCCGAAA CAGGAG 36 36 base pairs nucleic acid single linear 531 GGGUUAGCUG AUGAGGCCGA AAGGCCGAAA CUGGGG 36 36 base pairs nucleic acid single linear 532 CCGGGGUCUG AUGAGGCCGA AAGGCCGAAA GAACUG 36 36 base pairs nucleic acid single linear 533 GACUGGGCUG AUGAGGCCGA AAGGCCGAAA GGACCC 36 36 base pairs nucleic acid single linear 534 UCAGCUUCUG AUGAGGCCGA AAGGCCGAAA GAAAAG 36 36 base pairs nucleic acid single linear 535 GGCUUCCCUG AUGAGGCCGA AAGGCCGAAA CAGCGU 36 36 base pairs nucleic acid single linear 536 AGCAUCACUG AUGAGGCCGA AAGGCCGAAA CUGCAG 36 36 base pairs nucleic acid single linear 537 CAGCAUCCUG AUGAGGCCGA AAGGCCGAAA ACUGCA 36 36 base pairs nucleic acid single linear 538 GCCAAGCCUG AUGAGGCCGA AAGGCCGAAA GGCCCC 36 36 base pairs nucleic acid single linear 539 UGUUGCCCUG AUGAGGCCGA AAGGCCGAAA GCAAGG 36 36 base pairs nucleic acid single linear 540 GUCUGUGCUG AUGAGGCCGA AAGGCCGAAA CACUCC 36 36 base pairs nucleic acid single linear 541 GGUCUGUCUG AUGAGGCCGA AAGGCCGAAA ACACUC 36 36 base pairs nucleic acid single linear 542 GUCCACACUG AUGAGGCCGA AAGGCCGAAA UGCCAG 36 36 base pairs nucleic acid single linear 543 AGUUCCCCUG AUGAGGCCGA AAGGCCGAAA CCGAAG 36 36 base pairs nucleic acid single linear 544 AAACUCUCUG AUGAGGCCGA AAGGCCGAAA GUUGUC 36 36 base pairs nucleic acid single linear 545 CUGCUGACUG AUGAGGCCGA AAGGCCGAAA CUCUGA 36 36 base pairs nucleic acid single linear 546 GCUGCUGCUG AUGAGGCCGA AAGGCCGAAA ACUCUG 36 36 base pairs nucleic acid single linear 547 AGCUGCUCUG AUGAGGCCGA AAGGCCGAAA AACUCU 36 36 base pairs nucleic acid single linear 548 ACACAGGCUG AUGAGGCCGA AAGGCCGAAA UGCACC 36 36 base pairs nucleic acid single linear 549 UUCAGGGCUG AUGAGGCCGA AAGGCCGAAA CUCCAU 36 36 base pairs nucleic acid single linear 550 CGAGUUACUG AUGAGGCCGA AAGGCCGAAA GCUUCA 36 36 base pairs nucleic acid single linear 551 GGCGAGUCUG AUGAGGCCGA AAGGCCGAAA UAGCUU 36 36 base pairs nucleic acid single linear 552 ACCAGGCCUG AUGAGGCCGA AAGGCCGAAA GUUAUA 36 36 base pairs nucleic acid single linear 553 CCCUCUCCUG AUGAGGCCGA AAGGCCGAAA GGAGAG 36 36 base pairs nucleic acid single linear 554 GGGGCAGCUG AUGAGGCCGA AAGGCCGAAA GCUGGG 36 36 base pairs nucleic acid single linear 555 CCUACCGCUG AUGAGGCCGA AAGGCCGAAA GCAGGA 36 36 base pairs nucleic acid single linear 556 CAUUGGGCUG AUGAGGCCGA AAGGCCGAAA GCCCCG 36 36 base pairs nucleic acid single linear 557 CUGGGCACUG AUGAGGCCGA AAGGCCGAAA GGUCAG 36 36 base pairs nucleic acid single linear 558 CACCUGGCUG AUGAGGCCGA AAGGCCGAAA GCAGAG 36 36 base pairs nucleic acid single linear 559 UCACCUGCUG AUGAGGCCGA AAGGCCGAAA AGCAGA 36 36 base pairs nucleic acid single linear 560 ACCUCCGCUG AUGAGGCCGA AAGGCCGAAA AGCGAG 36 36 base pairs nucleic acid single linear 561 GGAGGAGCUG AUGAGGCCGA AAGGCCGAAA GUCUUC 36 36 base pairs nucleic acid single linear 562 UGGAGGACUG AUGAGGCCGA AAGGCCGAAA AGUCUU 36 36 base pairs nucleic acid single linear 563 AAUGGAGCUG AUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 base pairs nucleic acid single linear 564 CGCAAUGCUG AUGAGGCCGA AAGGCCGAAA GGAGAA 36 36 base pairs nucleic acid single linear 565 UGUCCGCCUG AUGAGGCCGA AAGGCCGAAA UGGAGG 36 36 base pairs nucleic acid single linear 566 AGCAGAGCUG AUGAGGCCGA AAGGCCGAAA GUCCAU 36 36 base pairs nucleic acid single linear 567 GAGCAGACUG AUGAGGCCGA AAGGCCGAAA AGUCCA 36 36 base pairs nucleic acid single linear 568 AAGAGCACUG AUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 base pairs nucleic acid single linear 569 CUGAUCUCUG AUGAGGCCGA AAGGCCGAAA CUCAAA 36 36 base pairs nucleic acid single linear 570 AGGAGCUCUG AUGAGGCCGA AAGGCCGAAA UCUGAC 36 36 base pairs nucleic acid single linear 571 ACCUUAGCUG AUGAGGCCGA AAGGCCGAAA GCUGAU 36 36 base pairs nucleic acid single linear 572 AGCACCUCUG AUGAGGCCGA AAGGCCGAAA GGAGCU 36 36 base pairs nucleic acid single linear 573 CUCUUGGCUG AUGAGGCCGA AAGGCCGAAA GCACUG 36 36 base pairs nucleic acid single linear 574 UACAGACCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acid single linear 575 CACUACACUG AUGAGGCCGA AAGGCCGAAA CGAGCC 36 36 base pairs nucleic acid single linear 576 CGUGCACCUG AUGAGGCCGA AAGGCCGAAA CAGACG 36 36 base pairs nucleic acid single linear 577 GAGGGGGCUG AUGAGGCCGA AAGGCCGAAA CAGUUC 36 36 base pairs nucleic acid single linear 578 UGAGGGGCUG AUGAGGCCGA AAGGCCGAAA ACAGUU 36 36 base pairs nucleic acid single linear 579 GGAAGAUCUG AUGAGGCCGA AAGGCCGAAA GGGGGA 36 36 base pairs nucleic acid single linear 580 CCGGGAACUG AUGAGGCCGA AAGGCCGAAA UGAGGG 36 36 base pairs nucleic acid single linear 581 UGCCGGGCUG AUGAGGCCGA AAGGCCGAAA GAUGAG 36 36 base pairs nucleic acid single linear 582 CUGCCGGCUG AUGAGGCCGA AAGGCCGAAA AGAUGA 36 36 base pairs nucleic acid single linear 583 GGGGCCACUG AUGAGGCCGA AAGGCCGAAA GGCCUG 36 36 base pairs nucleic acid single linear 584 CUCCACACUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear 585 GCUCAAUCUG AUGAGGCCGA AAGGCCGAAA UCUCCA 36 36 base pairs nucleic acid single linear 586 GCUGCUCCUG AUGAGGCCGA AAGGCCGAAA UGAUCU 36 36 base pairs nucleic acid single linear 587 GUAGCGGCUG AUGAGGCCGA AAGGCCGAAA GCGCAU 36 36 base pairs nucleic acid single linear 588 UGUAGCGCUG AUGAGGCCGA AAGGCCGAAA AGCGCA 36 36 base pairs nucleic acid single linear 589 GCACUUGCUG AUGAGGCCGA AAGGCCGAAA GCGGAA 36 36 base pairs nucleic acid single linear 590 GCCCGCGCUG AUGAGGCCGA AAGGCCGAAA GCGCCC 36 36 base pairs nucleic acid single linear 591 CGCCUGGCUG AUGAGGCCGA AAGGCCGAAA UGCUGC 36 36 base pairs nucleic acid single linear 592 UUGGUGGCUG AUGAGGCCGA AAGGCCGAAA UCUGUG 36 36 base pairs nucleic acid single linear 593 UGAUCUUCUG AUGAGGCCGA AAGGCCGAAA UGGUGG 36 36 base pairs nucleic acid single linear 594 AGCCAUUCUG AUGAGGCCGA AAGGCCGAAA UCUUGA 36 36 base pairs nucleic acid single linear 595 UCCUGUGCUG AUGAGGCCGA AAGGCCGAAA GCCAUU 36 36 base pairs nucleic acid single linear 596 CCAGGGACUG AUGAGGCCGA AAGGCCGAAA UGCGCA 36 36 base pairs nucleic acid single linear 597 GACCAGGCUG AUGAGGCCGA AAGGCCGAAA GAUGCG 36 36 base pairs nucleic acid single linear 598 CCUUGGUCUG AUGAGGCCGA AAGGCCGAAA CCAGGG 36 36 base pairs nucleic acid single linear 599 CGGUGAGCUG AUGAGGCCGA AAGGCCGAAA GGGUCC 36 36 base pairs nucleic acid single linear 600 GGCCGGUCUG AUGAGGCCGA AAGGCCGAAA GGAGGG 36 36 base pairs nucleic acid single linear 601 UGGGGGUCUG AUGAGGCCGA AAGGCCGAAA GGCCGG 36 36 base pairs nucleic acid single linear 602 UUCCUACCUG AUGAGGCCGA AAGGCCGAAA GCUCGU 36 36 base pairs nucleic acid single linear 603 CCUUUCCCUG AUGAGGCCGA AAGGCCGAAA CAAGCU 36 36 base pairs nucleic acid single linear 604 CUCAUAGCUG AUGAGGCCGA AAGGCCGAAA GCCAUC 36 36 base pairs nucleic acid single linear 605 CCUCAUACUG AUGAGGCCGA AAGGCCGAAA AGCCAU 36 36 base pairs nucleic acid single linear 606 AGCCUCACUG AUGAGGCCGA AAGGCCGAAA GAAGCC 36 36 base pairs nucleic acid single linear 607 CCGGGCACUG AUGAGGCCGA AAGGCCGAAA GCUCAG 36 36 base pairs nucleic acid single linear 608 AACUGUGCUG AUGAGGCCGA AAGGCCGAAA UGCAGC 36 36 base pairs nucleic acid single linear 609 UUCUGGACUG AUGAGGCCGA AAGGCCGAAA CUGUGG 36 36 base pairs nucleic acid single linear 610 GUUCUGGCUG AUGAGGCCGA AAGGCCGAAA ACUGUG 36 36 base pairs nucleic acid single linear 611 GGUUCUGCUG AUGAGGCCGA AAGGCCGAAA AACUGU 36 36 base pairs nucleic acid single linear 612 CACACUGCUG AUGAGGCCGA AAGGCCGAAA UUCCCA 36 36 base pairs nucleic acid single linear 613 UGACUGACUG AUGAGGCCGA AAGGCCGAAA GCCUGC 36 36 base pairs nucleic acid single linear 614 GCUGACUCUG AUGAGGCCGA AAGGCCGAAA UAGCCU 36 36 base pairs nucleic acid single linear 615 AUGCGCUCUG AUGAGGCCGA AAGGCCGAAA CUGAUA 36 36 base pairs nucleic acid single linear 616 UGGUCUGCUG AUGAGGCCGA AAGGCCGAAA UGCGCU 36 36 base pairs nucleic acid single linear 617 AACUUGGCUG AUGAGGCCGA AAGGCCGAAA GGGGUU 36 36 base pairs nucleic acid single linear 618 GAACUUGCUG AUGAGGCCGA AAGGCCGAAA AGGGGU 36 36 base pairs nucleic acid single linear 619 CUAUAGGCUG AUGAGGCCGA AAGGCCGAAA CUUGGA 36 36 base pairs nucleic acid single linear 620 UCUAUAGCUG AUGAGGCCGA AAGGCCGAAA ACUUGG 36 36 base pairs nucleic acid single linear 621 UCUUCUACUG AUGAGGCCGA AAGGCCGAAA GGAACU 36 36 base pairs nucleic acid single linear 622 GCUCUUCCUG AUGAGGCCGA AAGGCCGAAA UAGGAA 36 36 base pairs nucleic acid single linear 623 CAGGUCGCUG AUGAGGCCGA AAGGCCGAAA GUCCCC 36 36 base pairs nucleic acid single linear 624 GGAAGCACUG AUGAGGCCGA AAGGCCGAAA GCCGCA 36 36 base pairs nucleic acid single linear 625 CACCUGGCUG AUGAGGCCGA AAGGCCGAAA GCAGAG 36 36 base pairs nucleic acid single linear 626 UCACCUGCUG AUGAGGCCGA AAGGCCGAAA AGCAGA 36 36 base pairs nucleic acid single linear 627 CCUGCCUCUG AUGAGGCCGA AAGGCCGAAA UGGGUC 36 36 base pairs nucleic acid single linear 628 GCAGGCGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear 629 GAGGAAGCUG AUGAGGCCGA AAGGCCGAAA CAGGCG 36 36 base pairs nucleic acid single linear 630 GAUGAGGCUG AUGAGGCCGA AAGGCCGAAA GGACAG 36 36 base pairs nucleic acid single linear 631 GGAUGAGCUG AUGAGGCCGA AAGGCCGAAA AGGACA 36 36 base pairs nucleic acid single linear 632 AUGGGAUCUG AUGAGGCCGA AAGGCCGAAA GGAAGG 36 36 base pairs nucleic acid single linear 633 AAGAUGGCUG AUGAGGCCGA AAGGCCGAAA UGAGGA 36 36 base pairs nucleic acid single linear 634 UGUCAAACUG AUGAGGCCGA AAGGCCGAAA UGGGAU 36 36 base pairs nucleic acid single linear 635 AUUGUCACUG AUGAGGCCGA AAGGCCGAAA GAUGGG 36 36 base pairs nucleic acid single linear 636 GAUUGUCCUG AUGAGGCCGA AAGGCCGAAA AGAUGG 36 36 base pairs nucleic acid single linear 637 GGGGCACCUG AUGAGGCCGA AAGGCCGAAA UUGUCA 36 36 base pairs nucleic acid single linear 638 AGAUCUUCUG AUGAGGCCGA AAGGCCGAAA GCUCGG 36 36 base pairs nucleic acid single linear 639 CUCGGCACUG AUGAGGCCGA AAGGCCGAAA UCUUGA 36 36 base pairs nucleic acid single linear 640 GCUGCCACUG AUGAGGCCGA AAGGCCGAAA GUUUCG 36 36 base pairs nucleic acid single linear 641 CCCCACCCUG AUGAGGCCGA AAGGCCGAAA GGCAGC 36 36 base pairs nucleic acid single linear 642 GUAGGAACUG AUGAGGCCGA AAGGCCGAAA UCUCAU 36 36 base pairs nucleic acid single linear 643 CAGUAGGCUG AUGAGGCCGA AAGGCCGAAA GAUCUC 36 36 base pairs nucleic acid single linear 644 ACAGUAGCUG AUGAGGCCGA AAGGCCGAAA AGAUCU 36 36 base pairs nucleic acid single linear 645 CACACAGCUG AUGAGGCCGA AAGGCCGAAA GGAAGA 36 36 base pairs nucleic acid single linear 646 ACACCUCCUG AUGAGGCCGA AAGGCCGAAA UGUCCU 36 36 base pairs nucleic acid single linear 647 CGUGAAACUG AUGAGGCCGA AAGGCCGAAA CACCUC 36 36 base pairs nucleic acid single linear 648 CCCGUGACUG AUGAGGCCGA AAGGCCGAAA UACACC 36 36 base pairs nucleic acid single linear 649 UCCCGUGCUG AUGAGGCCGA AAGGCCGAAA AUACAC 36 36 base pairs nucleic acid single linear 650 GUCCCGUCUG AUGAGGCCGA AAGGCCGAAA AAUACA 36 36 base pairs nucleic acid single linear 651 CGAAAAGCUG AUGAGGCCGA AAGGCCGAAA GCCUCG 36 36 base pairs nucleic acid single linear 652 UUGCGAACUG AUGAGGCCGA AAGGCCGAAA GGAGCC 36 36 base pairs nucleic acid single linear 653 CUUGCGACUG AUGAGGCCGA AAGGCCGAAA AGGAGC 36 36 base pairs nucleic acid single linear 654 GCUUGCGCUG AUGAGGCCGA AAGGCCGAAA AAGGAG 36 36 base pairs nucleic acid single linear 655 AGCUUGCCUG AUGAGGCCGA AAGGCCGAAA AAAGGA 36 36 base pairs nucleic acid single linear 656 GGAACACCUG AUGAGGCCGA AAGGCCGAAA UGGCCA 36 36 base pairs nucleic acid single linear 657 GGUCCGGCUG AUGAGGCCGA AAGGCCGAAA CACAAU 36 36 base pairs nucleic acid single linear 658 GGGUCCGCUG AUGAGGCCGA AAGGCCGAAA ACACAA 36 36 base pairs nucleic acid single linear 659 GCGUAGGCUG AUGAGGCCGA AAGGCCGAAA GGGGUC 36 36 base pairs nucleic acid single linear 660 GUCUGCGCUG AUGAGGCCGA AAGGCCGAAA GGGAGG 36 36 base pairs nucleic acid single linear 661 CGCACAGCUG AUGAGGCCGA AAGGCCGAAA GCCUGC 36 36 base pairs nucleic acid single linear 662 GCAUGGACUG AUGAGGCCGA AAGGCCGAAA CACGCA 36 36 base pairs nucleic acid single linear 663 CUGCAUGCUG AUGAGGCCGA AAGGCCGAAA GACACG 36 36 base pairs nucleic acid single linear 664 CGGUCGGCUG AUGAGGCCGA AAGGCCGAAA GGCCGC 36 36 base pairs nucleic acid single linear 665 CCGGUCGCUG AUGAGGCCGA AAGGCCGAAA AGGCCG 36 36 base pairs nucleic acid single linear 666 GCUCACUCUG AUGAGGCCGA AAGGCCGAAA GCUCCC 36 36 base pairs nucleic acid single linear 667 GUACUGGCUG AUGAGGCCGA AAGGCCGAAA UUCCAU 36 36 base pairs nucleic acid single linear 668 GGUACUGCUG AUGAGGCCGA AAGGCCGAAA AUUCCA 36 36 base pairs nucleic acid single linear 669 UGGCAGGCUG AUGAGGCCGA AAGGCCGAAA CUGGAA 36 36 base pairs nucleic acid single linear 670 UCGUCUGCUG AUGAGGCCGA AAGGCCGAAA UCUGGC 36 36 base pairs nucleic acid single linear 671 CGGUGACCUG AUGAGGCCGA AAGGCCGAAA UCGUCU 36 36 base pairs nucleic acid single linear 672 AUCCGGUCUG AUGAGGCCGA AAGGCCGAAA CGAUCG 36 36 base pairs nucleic acid single linear 673 UCUCCUCCUG AUGAGGCCGA AAGGCCGAAA UCCGGU 36 36 base pairs nucleic acid single linear 674 GUCCUUUCUG AUGAGGCCGA AAGGCCGAAA CGUUUC 36 36 base pairs nucleic acid single linear 675 GGUCUCACUG AUGAGGCCGA AAGGCCGAAA UGUCCU 36 36 base pairs nucleic acid single linear 676 GCUCUUGCUG AUGAGGCCGA AAGGCCGAAA GGUCUC 36 36 base pairs nucleic acid single linear 677 UGCUCUUCUG AUGAGGCCGA AAGGCCGAAA AGGUCU 36 36 base pairs nucleic acid single linear 678 UCUUCAUCUG AUGAGGCCGA AAGGCCGAAA UGCUCU 36 36 base pairs nucleic acid single linear 679 CUGAAAGCUG AUGAGGCCGA AAGGCCGAAA CUCUUC 36 36 base pairs nucleic acid single linear 680 CCGCUGACUG AUGAGGCCGA AAGGCCGAAA GGACUC 36 36 base pairs nucleic acid single linear 681 UCCGCUGCUG AUGAGGCCGA AAGGCCGAAA AGGACU 36 36 base pairs nucleic acid single linear 682 GUCCGCUCUG AUGAGGCCGA AAGGCCGAAA AAGGAC 36 36 base pairs nucleic acid single linear 683 CGAGGUGCUG AUGAGGCCGA AAGGCCGAAA GGCCGG 36 36 base pairs nucleic acid single linear 684 AUGCGUCCUG AUGAGGCCGA AAGGCCGAAA GGUGGA 36 36 base pairs nucleic acid single linear 685 GCACAGCCUG AUGAGGCCGA AAGGCCGAAA UGCGUC 36 36 base pairs nucleic acid single linear 686 CUGCGGGCUG AUGAGGCCGA AAGGCCGAAA GGCACA 36 36 base pairs nucleic acid single linear 687 GCUGCGGCUG AUGAGGCCGA AAGGCCGAAA AGGCAC 36 36 base pairs nucleic acid single linear 688 AGAAGCUCUG AUGAGGCCGA AAGGCCGAAA GCUGCG 36 36 base pairs nucleic acid single linear 689 GGGACAGCUG AUGAGGCCGA AAGGCCGAAA GCUGAG 36 36 base pairs nucleic acid single linear 690 GGGGACACUG AUGAGGCCGA AAGGCCGAAA AGCUGA 36 36 base pairs nucleic acid single linear 691 GCUUGGGCUG AUGAGGCCGA AAGGCCGAAA CAGAAG 36 36 base pairs nucleic acid single linear 692 AAAGGGACUG AUGAGGCCGA AAGGCCGAAA GGGCUG 36 36 base pairs nucleic acid single linear 693 GUAAAGGCUG AUGAGGCCGA AAGGCCGAAA UAGGGC 36 36 base pairs nucleic acid single linear 694 UGACGUACUG AUGAGGCCGA AAGGCCGAAA GGGAUA 36 36 base pairs nucleic acid single linear 695 AUGACGUCUG AUGAGGCCGA AAGGCCGAAA AGGGAU 36 36 base pairs nucleic acid single linear 696 GAUGACGCUG AUGAGGCCGA AAGGCCGAAA AAGGGA 36 36 base pairs nucleic acid single linear 697 CAGGGAUCUG AUGAGGCCGA AAGGCCGAAA CGUAAA 36 36 base pairs nucleic acid single linear 698 GCUCAGGCUG AUGAGGCCGA AAGGCCGAAA UGACGU 36 36 base pairs nucleic acid single linear 699 CAUAGUUCUG AUGAGGCCGA AAGGCCGAAA UGGUGC 36 36 base pairs nucleic acid single linear 700 CUCAUCACUG AUGAGGCCGA AAGGCCGAAA GUUGAU 36 36 base pairs nucleic acid single linear 701 GGUGGGACUG AUGAGGCCGA AAGGCCGAAA CUCAUC 36 36 base pairs nucleic acid single linear 702 UGGUGGGCUG AUGAGGCCGA AAGGCCGAAA ACUCAU 36 36 base pairs nucleic acid single linear 703 AUGGUGGCUG AUGAGGCCGA AAGGCCGAAA AACUCA 36 36 base pairs nucleic acid single linear 704 AGAAGGACUG AUGAGGCCGA AAGGCCGAAA CACCAU 36 36 base pairs nucleic acid single linear 705 CAGAAGGCUG AUGAGGCCGA AAGGCCGAAA ACACCA 36 36 base pairs nucleic acid single linear 706 CCAGAAGCUG AUGAGGCCGA AAGGCCGAAA AACACC 36 36 base pairs nucleic acid single linear 707 UGCCCAGCUG AUGAGGCCGA AAGGCCGAAA GGAAAC 36 36 base pairs nucleic acid single linear 708 CUGCCCACUG AUGAGGCCGA AAGGCCGAAA AGGAAA 36 36 base pairs nucleic acid single linear 709 CCUGGCUCUG AUGAGGCCGA AAGGCCGAAA UCUGCC 36 36 base pairs nucleic acid single linear 710 CAAGGCCCUG AUGAGGCCGA AAGGCCGAAA GGCCUG 36 36 base pairs nucleic acid single linear 711 CGGGGCCCUG AUGAGGCCGA AAGGCCGAAA GGCCGA 36 36 base pairs nucleic acid single linear 712 ACUUGGGCUG AUGAGGCCGA AAGGCCGAAA GGGGCC 36 36 base pairs nucleic acid single linear 713 GGGGCAGCUG AUGAGGCCGA AAGGCCGAAA CUUGGG 36 36 base pairs nucleic acid single linear 714 GGGGCUGCUG AUGAGGCCGA AAGGCCGAAA GCCUGG 36 36 base pairs nucleic acid single linear 715 AUGGCUGCUG AUGAGGCCGA AAGGCCGAAA GCAGGG 36 36 base pairs nucleic acid single linear 716 GAGCUGACUG AUGAGGCCGA AAGGCCGAAA CCAUGG 36 36 base pairs nucleic acid single linear 717 CAGAGCUCUG AUGAGGCCGA AAGGCCGAAA UACCAU 36 36 base pairs nucleic acid single linear 718 UGGGCCACUG AUGAGGCCGA AAGGCCGAAA GCUGAU 36 36 base pairs nucleic acid single linear 719 GGACUGGCUG AUGAGGCCGA AAGGCCGAAA CAGGGG 36 36 base pairs nucleic acid single linear 720 GGGCUAGCUG AUGAGGCCGA AAGGCCGAAA CUGGGA 36 36 base pairs nucleic acid single linear 721 CUGGGGCCUG AUGAGGCCGA AAGGCCGAAA GGACUG 36 36 base pairs nucleic acid single linear 722 GCCUGAGCUG AUGAGGCCGA AAGGCCGAAA GGGCCU 36 36 base pairs nucleic acid single linear 723 ACAGCCUCUG AUGAGGCCGA AAGGCCGAAA GGAGGG 36 36 base pairs nucleic acid single linear 724 GGCCUCUCUG AUGAGGCCGA AAGGCCGAAA CAGCGU 36 36 base pairs nucleic acid single linear 725 AUCAUCACUG AUGAGGCCGA AAGGCCGAAA CUGCAG 36 36 base pairs nucleic acid single linear 726 CAUCAUCCUG AUGAGGCCGA AAGGCCGAAA ACUGCA 36 36 base pairs nucleic acid single linear 727 GCCAAGCCUG AUGAGGCCGA AAGGCCGAAA GGCCCC 36 36 base pairs nucleic acid single linear 728 UGUUGCCCUG AUGAGGCCGA AAGGCCGAAA GCAAGG 36 36 base pairs nucleic acid single linear 729 GUCUGUGCUG AUGAGGCCGA AAGGCCGAAA CACAGC 36 36 base pairs nucleic acid single linear 730 GGUCUGUCUG AUGAGGCCGA AAGGCCGAAA ACACAG 36 36 base pairs nucleic acid single linear 731 GUCGACGCUG AUGAGGCCGA AAGGCCGAAA UGCCAG 36 36 base pairs nucleic acid single linear 732 AGUUGUCCUG AUGAGGCCGA AAGGCCGAAA CGGAUG 36 36 base pairs nucleic acid single linear 733 AAACUCGCUG AUGAGGCCGA AAGGCCGAAA GUUGUC 36 36 base pairs nucleic acid single linear 734 CUGCUGACUG AUGAGGCCGA AAGGCCGAAA CUCGGA 36 36 base pairs nucleic acid single linear 735 GCUGCUGCUG AUGAGGCCGA AAGGCCGAAA ACUCGG 36 36 base pairs nucleic acid single linear 736 AGCUGCUCUG AUGAGGCCGA AAGGCCGAAA AACUCG 36 36 base pairs nucleic acid single linear 737 CCACAGGCUG AUGAGGCCGA AAGGCCGAAA UGCCCU 36 36 base pairs nucleic acid single linear 738 CUCAGGGCUG AUGAGGCCGA AAGGCCGAAA CUCCAU 36 36 base pairs nucleic acid single linear 739 CGAGUUACUG AUGAGGCCGA AAGGCCGAAA GCCUCA 36 36 base pairs nucleic acid single linear 740 GGCGAGUCUG AUGAGGCCGA AAGGCCGAAA UAGCCU 36 36 base pairs nucleic acid single linear 741 ACUAGGCCUG AUGAGGCCGA AAGGCCGAAA GUUAUA 36 36 base pairs nucleic acid single linear 742 CUGUCACCUG AUGAGGCCGA AAGGCCGAAA GGCGAG 36 36 base pairs nucleic acid single linear 743 GGAGCAGCUG AUGAGGCCGA AAGGCCGAAA GCUGGG 36 36 base pairs nucleic acid single linear 744 CCCAGUGCUG AUGAGGCCGA AAGGCCGAAA GCAGGA 36 36 base pairs nucleic acid single linear 745 CAUUGGGCUG AUGAGGCCGA AAGGCCGAAA GCCCCG 36 36 base pairs nucleic acid single linear 746 CUGAAAGCUG AUGAGGCCGA AAGGCCGAAA GGCCAU 36 36 base pairs nucleic acid single linear 747 CUCCUGACUG AUGAGGCCGA AAGGCCGAAA GGAGGC 36 36 base pairs nucleic acid single linear 748 UCUCCUGCUG AUGAGGCCGA AAGGCCGAAA AGGAGG 36 36 base pairs nucleic acid single linear 749 AUCUCCUCUG AUGAGGCCGA AAGGCCGAAA AAGGAG 36 36 base pairs nucleic acid single linear 750 GGAGGAGCUG AUGAGGCCGA AAGGCCGAAA GUCUUC 36 36 base pairs nucleic acid single linear 751 UGGAGGACUG AUGAGGCCGA AAGGCCGAAA AGUCUU 36 36 base pairs nucleic acid single linear 752 AAUGGAGCUG AUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 base pairs nucleic acid single linear 753 CGCAAUGCUG AUGAGGCCGA AAGGCCGAAA GGAGAA 36 36 base pairs nucleic acid single linear 754 UGUCCGCCUG AUGAGGCCGA AAGGCCGAAA UGGAGG 36 36 base pairs nucleic acid single linear 755 GGCUGAGCUG AUGAGGCCGA AAGGCCGAAA GUCCAU 36 36 base pairs nucleic acid single linear 756 GGGCUGACUG AUGAGGCCGA AAGGCCGAAA AGUCCA 36 36 base pairs nucleic acid single linear 757 CAGGGCUCUG AUGAGGCCGA AAGGCCGAAA GAAGUC 36 36 base pairs nucleic acid single linear 758 CUGAUCUCUG AUGAGGCCGA AAGGCCGAAA CUCAGC 36 36 base pairs nucleic acid single linear 759 AGGAGCUCUG AUGAGGCCGA AAGGCCGAAA UCUGAC 36 36 base pairs nucleic acid single linear 760 CCCUUAGCUG AUGAGGCCGA AAGGCCGAAA GCUGAU 36 36 base pairs nucleic acid single linear 761 ACCCCCUCUG AUGAGGCCGA AAGGCCGAAA GGAGCU 36 36 base pairs nucleic acid single linear 762 CUCUGGGCUG AUGAGGCCGA AAGGCCGAAA GGGCAG 36 52 base pairs nucleic acid single linear 763 UGAGGGGGAG AAGUUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 764 GCUGCUUGAG AAGCUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 765 GCCAUCCCAG AAGUCCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 766 GUUCUGGAAG AAGUGGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 767 GAAGGACAAG AAGCAGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 768 UUGAGCUCAG AAGUGUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 769 CCCACCGAAG AAGCUGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 770 AGGCUGGGAG AAGCGUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 771 GGUCGGAAAG AAGCCGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 772 UGACGAUCAG AAGUAUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 773 GUCGGUGGAG AAGCUGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 774 GGCCGGGGAG AAGUGGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 775 CAUCAUCAAG AAGCAGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 776 ACAGCUGGAG AAGUGCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 777 GAUGCCAGAG AAGUGAACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 16 base pairs nucleic acid single linear 778 GAACUGUUCC CCCUCA 16 16 base pairs nucleic acid single linear 779 GAGCAGCCCA AGCAGC 16 16 base pairs nucleic acid single linear 780 GGACUGCCGG GAUGGC 16 16 base pairs nucleic acid single linear 781 CCACAGUUUC CAGAAC 16 16 base pairs nucleic acid single linear 782 CUGCCGCCUG UCCUUC 16 16 base pairs nucleic acid single linear 783 ACACUGCCGA GCUCAA 16 16 base pairs nucleic acid single linear 784 CAGCUGCCUC GGUGGG 16 16 base pairs nucleic acid single linear 785 ACGCAGACCC CAGCCU 16 16 base pairs nucleic acid single linear 786 CGGCGGCCUU CCGACC 16 16 base pairs nucleic acid single linear 787 AUACAGACGA UCGUCA 16 16 base pairs nucleic acid single linear 788 CAGCGGACCC ACCGAC 16 16 base pairs nucleic acid single linear 789 CCACCGACCC CCGGCC 16 16 base pairs nucleic acid single linear 790 CUGCAGUUUG AUGAUG 16 16 base pairs nucleic acid single linear 791 GCACAGACCC AGCUGU 16 16 base pairs nucleic acid single linear 792 UCACAGACCU GGCAUC 16 52 base pairs nucleic acid single linear 793 GUUGCUUCAG AAGUUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 794 GAGAUUCGAG AAGUUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 795 GCCAUCCCAG AAGUCCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 796 GGGCAGAGAG AAGCCUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 797 UUGAGCUCAG AAGUGUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 798 CCCACCGAAG AAGCUCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 799 AGGCUGGGAG AAGCGUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 800 GAUCAGAAAG AAGCCGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 801 AGGUGUAGAG AAGCGGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 802 GGGCAGAGAG AAGUGCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 803 GGGCUUCCAG AAGCGUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 804 CAGCAUCAAG AAGCAGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 805 ACUCCUGGAG AAGUGCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 806 GAUGCCAGAG AAGUGAACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 807 AAGUCGGGAG AAGCUGACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 808 UGGCUCCAAG AAGUCCACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 809 UGGUGUCGAG AAGCACACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 810 AUUCUGAAAG AAGCCAACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 52 base pairs nucleic acid single linear 811 UCAGUAAAAG AAGUCUACCA GAGAAACACA CGUUGUGGUA CAUUACCUGG UA 52 16 base pairs nucleic acid single linear 812 GAACAGCCGA AGCAAC 16 16 base pairs nucleic acid single linear 813 GAACAGUUCG AAUCUC 16 16 base pairs nucleic acid single linear 814 GGACUGCCGG GAUGGC 16 16 base pairs nucleic acid single linear 815 AGGCUGACCU CUGCCC 16 16 base pairs nucleic acid single linear 816 ACACUGCCGA GCUCAA 16 16 base pairs nucleic acid single linear 817 GAGCUGCCUC GGUGGG 16 16 base pairs nucleic acid single linear 818 ACGCCGACCC CAGCCU 16 16 base pairs nucleic acid single linear 819 CGGCGGCCUU CUGAUC 16 16 base pairs nucleic acid single linear 820 CCGCAGCCCU ACACCU 16 16 base pairs nucleic acid single linear 821 GCACCGUCCU CUGCCC 16 16 base pairs nucleic acid single linear 822 ACGCUGUCGG AAGCCC 16 16 base pairs nucleic acid single linear 823 CUGCAGUUUG AUGCUG 16 16 base pairs nucleic acid single linear 824 GCACAGACCC AGGAGU 16 16 base pairs nucleic acid single linear 825 UCACAGACCU GGCAUC 16 16 base pairs nucleic acid single linear 826 CAGCUGCCCC CGACUU 16 16 base pairs nucleic acid single linear 827 GGACAGACUG GAGCCA 16 16 base pairs nucleic acid single linear 828 GUGCUGCCCG ACACCA 16 16 base pairs nucleic acid single linear 829 UGGCCGCCUU CAGAAU 16 16 base pairs nucleic acid single linear 830 AGACAGCCUU UACUGA 16

Claims

1. An enzymatic RNA molecule which cleaves rel A mRNA.

2. An enzymatic RNA molecule of claim 1, the binding arms of which contain sequences complementary to the sequences defined in Table II.

3. The enzymatic RNA molecule of claim 1, the binding arms of which contain sequences complementary to the sequences defined in any one of Tables III, and IV-VII

4. The enzymatic RNA molecule of claim 1, 2, or 3, wherein said RNA molecule is in a hammerhead motif.

5. The enzymatic RNA molecule of claim 1, 2, or 3, wherein said RNA molecule is in a hairpin, hepatitis delta virus, group 1 intron, VS RNA or RNAseP RNA motif.

6. The enzymatic RNA molecule of claim 6, wherein said ribozyme comprises between 12 and 100 bases complementary to said mRNA.

7. The enzymatic RNA molecule of claim 6, wherein said ribozyme comprises between 14 and 24 bases complementary to said mRNA.

8. Enzymatic RNA molecule consisting essentially of any sequence selected from the group of those shown in Tables IV, V, VI, and VII.

9. A mammalian cell including an enzymatic RNA molecule of claim 1, 2, or 3.

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

11. An expression vector including nucleic acid encoding an enzymatic RNA molecule or multiple enzymatic molecules of claim 1, 2, or 3 in a manner which allows expression of that enzymatic RNA molecule(s) within a mammalian cell.

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

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

14. A method for treatment of a condition related to the level of NF-κB activity by administering to a patient an enzymatic nucleic acid molecule of claim 1, 2, or 3,

15. A method for treatment of a condition related to the level of NF-κB activity by administering to a patient an expression vector of claim 11.

16. The method of claim 14 or 15, wherein said patient is a human.

17. The method of claim 14 wherein said condition is selected from the group consisting of restenosis, rheumatoid arthritis, asthma, inflammatory or autoimmune disorders, and transplant rejection.

18. The method of claim 15 wherein said condition is selected from the group consisting of restenosis, rheumatoid arthritis, asthma, inflammatory or autoimmune disorders, and transplant rejection.