Method and reagent for the treatment of diseases or conditions related to levels of vascular endothelial growth factor receptor

Abstract
Nucleic acid molecule which modulates the synthesis, expression and/or stability of an mRNA encoding one or more receptors of vascular endothelial growth factor.
Description




BACKGROUND OF THE INVENTION




This invention relates to methods and reagents for the treatment of diseases or conditions relating to the levels of expression of vascular endothelial growth factor (VEGF) receptor(s).




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




VEGF, also referred to as vascular permeability factor (VPF) and vasculotropin, is a potent and highly specific mitogen of vascular endothelial cells (for a review see Ferrara, 1993


Trends Cardiovas. Med.


3, 244; Neufeld et al., 1994


Prog. Growth Factor Res.


5, 89). VEGF induced neovascularization is implicated in various pathological conditions such as tumor angiogenesis, proliferative diabetic retinopathy, hypoxia-induced angiogenesis, rheumatoid arthritis, psoriasis, wound healing and others.




VEGF, an endothelial cell-specific mitogen, is a 34-45 kDa glycoprotein with a wide range of activities that include promotion of angiogenesis, enhancement of vascular-permeability and others. VEGF belongs to the platelet-derived growth factor (PDGF) family of growth factors with approximately 18% homology with the A and B chain of PDGF at the amino acid level. Additionally, VEGF contains the eight conserved cysteine residues common to all growth factors belonging to the PDGF family (Neufeld et al., supra). VEGF protein is believed to exist predominantly as disulfide-linked homodimers; monomers of VEGF have been shown to be inactive (Plouet et al., 1989


EMBO J.


8, 3801).




VEGF exerts its influence on vascular endothelial cells by binding to specific high-affinity cell surface receptors. Covalent cross-linking experiments with


125


I-labeled VEGF protein have led to the identification of three high molecular weight complexes of 225, 195 and 175 kDa presumed to be VEGF and VEGF receptor complexes (Vaisman et al., 1990


J. Biol. Chem.


265, 19461). Based on these studies VEGF-specific receptors of 180, 150 and 130 kDa molecular mass were predicted. In endothelial cells, receptors of 150 and the 130 kDa have been identified. The VEGF receptors belong to the superfamily of receptor tyrosine kinases (RTKs) characterized by a conserved cytoplasmic catalytic kinase domain and a hydrophylic kinase sequence. The extracellular domains of the VEGF receptors consist of seven immunoglobulin-like domains that are thought to be involved in VEGF binding functions.




The two most abundant and high-affinity receptors of VEGF are flt-1 (fms-like tyrosine kinase) cloned by Shibuya et al., 1990


Oncogene


5, 519 and KDR (kinase-insert-domain-containing receptor) cloned by Terman et al., 1991


Oncogene


6, 1677. The murine homolog of KDR, cloned by Mathews et al., 1991,


Proc. Natl. Acad. Sci.,


USA, 88, 9026, shares 85% amino acid homology with KDR and is termed as flk-1 (fetal liver kinase-1). Recently it has been shown that the high-affinity binding of VEGF to its receptors is modulated by cell surface-associated heparin and heparin-like molecules (Gitay-Goren et al, 1992


J. Biol. Chem.


267, 6093).




VEGF expression has been associated with several pathological states such as tumor angiogenesis, several forms of blindness, rheumatoid arthritis, psoriasis and others. Following is a brief summary of evidence supporting the involvement of VEGF in various diseases:




1) Tumor angiogenesis: Increased levels of VEGF gene expression have been reported in vascularized and edema-associated brain tumors (Berkman et al., 1993


J. Clini. Invest.


91, 153). A more direct demostration of the role of VEGF in tumor angiogenesis was demonstrated by Jim Kim et al., 1993


Nature


362,841 wherein, monoclonal antibodies against VEGF were successfully used to inhibit the growth of rhabdomyosarcoma, glioblastoma multiforme cells in nude mice. Similarly, expression of a dominant negative mutated form of the flt-1 VEGF receptor inhibits vascularization induced by human glioblastoma cells in nude mice (Millauer et al., 1994,


Nature


367, 576).




2) Ocular diseses: Aiello et al., 1994


New Engl. J. Med.


331, 1480, showed that the ocular fluid, of a majority of patients suffering from diabetic retinopathy and other retinal disorders, contains a high concentration of VEGF. Miller et al., 1994


Am. J. Pathol.


145, 574, reported elevated levels of VEGF mRNA in patients suffering from retinal ischemia. These observations support a direct role for VEGF in ocular diseases.




3) Psoriasis: Detmar et al., 1994


J. Exp. Med.


180, 1141 reported that VEGF and its receptors were over-expressed in psoriatic skin and psoriatic dermal microvessels, suggesting that VEGF plays a significant role in psoriasis.




4) Rheumatoid arthritis: Immunohistochemistry and in situ hybridization studies on tissues from the joints of patients suffering from rheumatoid arthritis show an increased level of VEGF and its receptors (Fava et al., 1994


J. Exp. Med.


180, 341). Additionally, Koch et al., 1994


J. Immunol.


152, 4149, found that VEGF-specific antibodies were able to significantly reduce the mitogenic activity of synovial tissues from patients suffering from rheumatoid arthritis. These observations support a direct role for VEGF in rheumatoid arthritis.




In addition to the above data on pathological conditions involving excessive angiogenesis, a number of studies have demonstrated that VEGF is both necessary and sufficient for neovascularization. Takashita et al., 1995


J. Clin. Invest.


93, 662, demonstrated that a single injection of VEGF augmented collateral vessel development in a rabbit model of ischemia. VEGF also can induce neovascularization when injected into the cornea. Expression of the VEGF gene in CHO cells is sufficient to confer tumorigenic potential to the cells. Kim et al., supra and Millauer et al., supra used monoclonal antibodies against VEGF or a dominant negative form of flk-1 receptor to inhibit tumor-induced neovascularization.




During development, VEGF and its receptors are associated with regions of new vascular growth (Millauer et al., 1993 Cell 72, 835; Shalaby et al., 1993


J. Clin. Invest.


91, 2235). Furthermore, transgenic mice lacking either of the VEGF receptors are defective in blood vessel formation, infact these mouse do not survive; flk-1 appears to be required for differentiation of endothelial cells, while flt-1 appears to be required at later stages of vessel formation (Shalaby et al., 1995


Nature


376, 62; Fung et al., 1995


Nature


376, 66). Thus, these receptors must be present to properly signal endothelial cells or their precursors to respond to vascularization-promoting stimuli.




All of the conditions listed above, involve extensive vascularization. This hyper-stimulation of endothelial cells may be alleviated by VEGF antagonists. Thus most of the therapeutic efforts for the above conditions have concentrated on finding inhibitors of the VEGF protein.




Kim et al., 1993


Nature


362, 841 have been successful in inhibiting VEGF-induced tumor growth and angiogenesis in nude mice by treating the mice with VEGF-specific monoclonal antibody.




Koch et al., 1994


J. Immunol.


152, 4149 showed that the mitogenic activity of microvascular endothelial cells found in rheumatoid arthritis (RA) synovial tissue explants and the chemotactic property of endothelial cells from RA synovial fluid can be neutralized significantly by treatment with VEGF-specific antibodies.




Ullrich et al., International PCT Publication No. WO 94/11499 and Millauer et al., 1994


Nature


367, 576 used a soluble form of flk-1 receptor (dominant-negative mutant) to prevent VEGF-mediated tumor angiogenesis in immunodeficient mice.




Kendall and Thomas, International PCT Publication No. WO 94/21679 describe the use of naturally occuring or recombinantly-engineered soluble forms of VEGF receptors to inhibit VEGF activity.




Robinson, International PCT Publication No. WO 95/04142 describes the use of antisense oligonucleotides targeted against VEGF RNA to inhibit VEGF expression.




Jellinek et al., 1994


Biochemistry


33, 10450 describe the use of VEGF-specific high-affinity RNA aptamers to inhibit the binding of VEGF to its receptors.




Rockwell and Goldstein, International PCT Publication No. WO 95/21868, describe the use of anti-VEGF receptor monoclonal antibodies to neutralize the the effect of VEGF on endothelial cells.




SUMMARY OF THE INVENTION




The invention features novel nucleic acid-based techniques [e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, 2-5A antisense chimeras, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups (Cook et al., U.S. Pat. No. 5,359,051)] and methods for their use to down regulate or inhibit the expression of receptors of VEGF (VEGF-R).




In a preferred embodiment, the invention features use of one or more of the nucleic acid-based techniques to inhibit the expression of flt-1 and/or flk-1 /KDR receptors.




By “inhibit” it is meant that the activity of VEGF-R or level of mRNAs or equivalent RNAs encoding VEGF-R is reduced below that observed in the absence of the nucleic acid. In one embodiment, inhibition with ribozymes preferably is below that level observed in the presence of an enzymatically inactive RNA molecule that is able to bind to the same site on the mRNA, but is unable to cleave that RNA. In another embodiment, inhibition with antisense oligonucleotides is preferably below that level observed in the presence of for example, an oligonucleotide with scrambled sequence or with mismatches.




By “enzymatic nucleic acid molecule” it is meant an RNA molecule which has complementarity in a substrate binding region to a specified gene target, and also has an enzymatic activity which is active to specifically cleave target RNA. That is, the enzymatic RNA molecule is able to intermolecularly cleave RNA and thereby inactivate a target RNA molecule. This complementary regions allow sufficient hybridization of the enzymatic RNA molecule to the target RNA and thus permit cleavage. One hundred percent complementarity is preferred, but complementarity as low as 50-75% may also be useful in this invention. By “equivalent” RNA to VEGF-R is meant to include those naturally occurring RNA molecules in various animals, including human, mice, rats, rabbits, primates and pigs.




By “antisense nucleic acid” it is meant a non-enzymatic nucleic acid molecule that binds to target RNA by means of RNA-RNA or RNA-DNA or RNA-PNA (protein nucleic acid; Egholm et al., 1993


Nature


365, 566) interactions and alters the activity of the target RNA (for a review see Stein and Cheng, 1993


Science


261, 1004).




By “2-5A antisense chimera” it is meant, an antisense oligonucleotide containing a 5′ phosphorylated 2′-5′-linked adenylate residues. These chimeras bind to target RNA in a sequence-specific manner and activate a cellular 2-5A-dependent ribonuclease which, in turn, cleaves the target RNA (Torrence et al., 1993


Proc. Natl. Acad. Sci. USA


90, 1300).




By “triplex DNA” it is meant an oligonucleotide that can bind to a double-stranded DNA in a sequence-specific manner to form a triple-strand helix. Formation of such triple helix structure has been shown to inhibit transcription of the targeted gene (Duval-Valentin et al., 1992


Proc. Natl. Acad. Sci. USA


89, 504).




By “gene” it is meant a nucleic acid that encodes an RNA.




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




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. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor of gene expression, 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.




Ribozymes that cleave the specified sites in VEGF-R mRNAs represent a novel therapeutic approach to treat tumor angiogenesis, ocular diseases, rhuematoid arthritis, psoriasis and others. Applicant indicates that ribozymes are able to inhibit the activity of VEGF-R (specifically flt-1 and flk-1/KDR) 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 VEGF-R mRNAs may be readily designed and are within the invention.




In preferred embodiments of this invention, the enzymatic nucleic acid molecule is formed in a hammerhead or hairpin motif, but may also be formed in the motif of a hepatitis delta virus, group I intron or RNaseP RNA (in association with an RNA guide sequence) or Neurospora VS RNA. Examples of such hammerhead motifs are described by Rossi et al., 1992,


AIDS Research and Human Retroviruses


8, 183, of hairpin motifs by Hampel et al., EP0360257, Hampel and Tritz, 1989


Biochemistry


28, 4929, and Hampel et al., 1990


Nucleic Acids Res.


18, 299, and an example of the hepatitis delta virus motif is described by Perrotta and Been, 1992


Biochemistry


31, 16; of the RNaseP motif by Guerrier-Takada et al., 1983


Cell


35, 849, Neurospora VS RNA ribozyme motif is described by Collins (Saville and Collins, 1990


Cell


61, 685-696; Saville and Collins, 1991


Proc. Natl. Acad. Sci. USA


88, 8826-8830; Collins and Olive, 1993


Biochemistry


32, 2795-2799) and of the Group I intron by Cech et al., U.S. Pat. No. 4,987,071. These specific motifs are not limiting in the invention and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule.




In a preferred embodiment the invention provides a method for producing a class of enzymatic cleaving agents which exhibit a high degree of specificity for the RNA of a desired target. The enzymatic nucleic acid molecule is preferably targeted to a highly conserved sequence region of target mRNAs encoding VEGF-R proteins (specifically flt-1 and flk-1/KDR) 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 tissue or cellular targets as required. Alternatively, the ribozymes can be expressed from DNA and/or RNA 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 nucleic acid motifs (e.g., antisense oligonucleotides, hammerhead or the hairpin ribozymes) are used for exogenous delivery. The simple structure of these molecules increases the ability of the nucleic acid to invade targeted regions of the mRNA structure. However, these nucleic acid molecules can also be expressed within cells from eukaryotic promoters (e.g., Izant and Weintraub, 1985


Science


229, 345; McGarry and Lindquist, 1986


Proc. Natl. Acad. Sci. USA


83, 399; SullengerScanlon et al., 1991,


Proc. Natl. Acad. Sci. USA,


88, 10591-5; Kashani-Sabet et al., 1992


Antisense Res. Dev.,


2, 3-15; Dropulic et al., 1992


J. Virol,


66, 1432-41; Weerasinghe et al., 1991


J. Virol,


65, 5531-4; Ojwang et al., 1992


Proc. Natl. Acad. Sci. USA


89, 10802-6; Chen et al., 1992


Nucleic Acids Res.,


20, 4581-9; Sarver et al., 1990


Science


247, 1222-1225; Thompson et al., 1995


Nucleic Acids Res.


23, 2259). Those skilled in the art realize that any nucleic acid can be expressed in eukaryotic cells from the appropriate DNA/RNA vector. The activity of such nucleic acids can be augmented by their release from the primary transcript by a ribozyme (Draper et al., PCT WO93/23569, and Sullivan et al., PCT WO94/02595, both hereby incorporated in their totality by reference herein; Ohkawa et al., 1992


Nucleic Acids Symp. Ser.,


27, 15-6; Taira et al., 1991,


Nucleic Acids Res.,


19, 5125-30; Ventura et al., 1993


Nucleic Acids Res.,


21, 3249-55; Chowrira et al., 1994


J. Biol. Chem.


269, 25856).




Such nucleic acids are useful for the prevention of the diseases and conditions discussed above, and any other diseases or conditions that are related to the levels of VEGF-R (specifically flt-1 and flk-1/KDR) in a cell or tissue.




By “related” is meant that the reduction of VEGF-R (specifically flt-1 and flk-1/KDR) RNA levels and thus reduction in the level of the respective protein 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 or tissues. The nucleic acid or nucleic acid complexes can be locally administered to relevant tissues ex vivo, or in vivo through injection, infusion pump or stent, with or without their incorporation in biopolymers. In preferred embodiments, the ribozymes have binding arms which are complementary to the sequences in Tables II to IX. Examples of such ribozymes also are shown in Tables II to IX. 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 RNA molecules and inhibit VEGF-R (specifically flt-1 and flk-1/KDR) activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the ribozymes are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of ribozymes. Such vectors might be repeatedly administered as necessary. Once expressed, the ribozymes cleave the target mRNA. Delivery of ribozyme expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that would allow for introduction into the desired target cell.




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




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











First the drawings will be described briefly.




DRAWINGS





FIG. 1

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





FIGS. 2



a


-


2




d:


is a diagrammatic representation of the hammerhead ribozyme domain known in the art;

FIG. 2



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



c


is a similar diagram showing the hammerhead divided by Haseloff and Gerlach (1988,


Nature ,


334, 585-591) into two portions; and

FIG. 2



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 diagramatic representation of the general structure of a hairpin ribozyme. Helix 2 (H2) is provided with a least 4 base pairs (i.e., n is 1, 2, 3 or 4) and helix 5 can be optionally provided of length 2 or more bases (preferably 3-20 bases, i.e., m is from 1-20 or more). Helix 2 and helix 5 may be covalently linked by one or more bases (i.e., r is ≧1 base). Helix 1, 4 or 5 may also be extended by 2 or more base pairs (e.g., 4-20 base pairs) to stabilize the ribozyme structure, and preferably is a protein binding site. In each instance, each N and N′ independently is any normal or modified base and each dash represents a potential base-pairing interaction. These nucleotides may be modified at the sugar, base or phosphate. Complete base-pairing is not required in the helices, but is preferred. Helix 1 and 4 can be of any size (i.e., o and p is each independently from 0 to any number, e.g., 20) as long as some base-pairing is maintained. Essential bases are shown as specific bases in the structure, but those in the art will recognize that one or more may be modified chemically (abasic, base, sugar and/or phosphate modifications) or replaced with another base without significant effect. Helix 4 can be formed from two separate molecules, i.e., without a connecting loop. The connecting loop when present may be a ribonucleotide with or without modifications to its base, sugar or phosphate. “q” is ≧2 bases. The connecting loop can also be replaced with a non-nucleotide linker molecule. H refers to bases A, U, or C. Y refers to pyrimidine bases. “_” refers to a covalent bond.





FIG. 4

is a representation of the general structure of the hepatitis delta virus ribozyme domain known in the art.





FIG. 5

is a representation of the general structure of the VS RNA ribozyme domain (SEQ ID NO:8).





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.





FIG. 7

shows the effect of hammerhead ribozymes targeted against flt-1 receptor on the binding of VEGF to the surface of human microvascular endothelial cells. Sequences of the ribozymes used are shown in Table II; the length of stem II region is 3 bp. The hammerhead ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions (see FIG.


11


); U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ terminus contains phosphorothioate substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose. The results of two separate experiments are shown as separate bars for each set. Each bar represents the average of triplicate samples. The standard deviation is shown with error bars. For the flt-1 data, 500 nM ribozyme (3:1 charge ratio with LipofectAMINE®) was used. Control 1-10 is the control for ribozymes 307-2797, control 11-20 is the control for ribozymes 3008-5585. The Control 1-10 and Control 11-20 represent the treatment of cells with LipofectAMINE® alone without any ribozymes.





FIG. 8

shows the effect of hammerhead ribozymes targeted against KDR receptor on the binding of VEGF to KDR on the surface of human microvascular endothelial cells. Sequences of the ribozymes used are shown in Table IV; the length of stem II region is 3 bp. The hammerhead ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions (see FIG.


11


); U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ terminus contains phosphorothioate substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose. The Control 1-10 and Control 11-20 represent the treatment of cells with LipofectAMINE® alone without any ribozymes. Irrel. RZ, is a control experiment wherein the cells are treated with a non-KDR-targeted ribozyme complexed with Lipofectamine®. 200 nM ribozyme (3:1 charge ratio with LipofectAMINE(®) was used. In addition to the KDR-targeted ribozymes, the effect on VEGF binding of a ribozyme targeted to an irrelevant mRNA (irrel. RZ) is also shown. Because the affinity of KDR for VEGF is about 10-fold lower than the affinity of flt-1 for VEGF, a higher concentration of VEGF was used in the binding assay.





FIG. 9

shows the specificity of hammerhead ribozymes targeted against flt-1 receptor. Inhibition of the binding of VEGF, urokinase plasminogen activator (UPA) and fibroblast growth factor (FGF) to their corresponding receptors as a function of anti-FLT ribozymes is shown. The sequence and description of the ribozymes used are as described under

FIG. 7

above. The average of triplicate samples is given; percent inhibition as calculated below.





FIG. 10

shows the inhibition of the proliferation of Human aortic endothelial cells (HAEC) mediated by phosphorothioate antisense oligodeoxynucleotides targeted against human KDR receptor RNA. Cell proliferation (O.D. 490) as a function of antisense oligodeoxynucleotide concentration is shown. KDR 21AS represents a 21 nt phosphorothioate antisense oligodeoxynucleotide targeted against KDR RNA. KDR 21 Scram represents a 21 nt phosphorothioate oligodeoxynucleotide having a scrambled sequence. LF represents the lipid carrier Lipofectin.





FIGS. 11

A-C show in vitro cleavage of flt-1 RNA by hammerhead ribozymes. A) diagrammatic representation of hammerhead ribozymes targeted against flt-1 RNA. The hammerhead (HH) ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ terminus contains phosphorothioate substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose (designated as 3′-iH). 1358 HH-A and 4229 HH-A contain 3 base-paired stem 11 region. 1358 HH-B and 4229 HH-B contain 4 base-paired stem II region. B) and C) shows in vitro cleavage kinetics of HH ribozymes targeted against sites 1358 and 4229 within the flt-1 RNA.





FIGS. 12

A-B show inhibition of human microvascular endothelial cell proliferation mediated by anti-flt-1 hammerhead ribozymes. A) Diagrammatic representation of hammerhead (HH) ribozymes targeted against sites 1358 and 4229 within the the flt-1 RNA. B) Graphical representation of the inhibition of cell proliferation mediated by 1358HH and 4229HH ribozymes.





FIG. 13

shows inhibition of human microvascular endothelial cell proliferation mediated by anti-KDR hammerhead ribozymes. The figure is a graphical representation of the inhibition of cell proliferation mediated by hammerhead ribozymes targeted against sites 527, 730, 3702 and 3950 within the KDR RNA. Irrelevant HH RZ is a hammerhead ribozyme targeted to an irrelevant target. All of these ribozymes, including the Irrelevant HH RZ, were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ termini contain phosphorothioate substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose (3′-iH).





FIG. 14

shows in vitro cleavage of KDR RNA by hammerhead ribozymes. The hammerhead (HH) ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose (designated as 3′-iH). 726 HH and 527 HH contain 4 base-paired stem II region. Percentin vitro cleavage kinetics as a function of time of HH ribozymes targeted against sites 527 and 726 within the KDR RNA is shown.





FIG. 15

shows in vitro cleavage of KDR RNA by hammerhead ribozymes. The hammerhead (HH) ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose (designated as 3′-iH). 3702 HH and 3950 HH contain 4 base-paired stem II region. Percentin vitro cleavage kinetics as a function of time of HH ribozymes targeted against sites 3702 and 3950 within the KDR RNA is shown.





FIG. 16

shows in vitro cleavage of RNA by hammerhead ribozymes that are targeted to sites that are conserved between flt-1 and KDR RNA. The hammerhead (HH) ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions. Additionally, the 3′end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose (designated as 3′-iH). FLT/KDR-I HH ribozyme was synthesized with either a 4 base-paired or a 3 base-paired stem II region. FLT/KDR-I HH can cleave site 3388 within flt-1 RNA and site 3151 within KDR RNA. Percentin vitro cleavage kinetics as a function of time of HH ribozymes targeted against sites 3702 and 3950 within the KDR RNA is shown.





FIG. 17

shows inhibition of human microvascular endothelial cell proliferation mediated by anti-KDR and anti-flt-1 hammerhead ribozymes. The figure is a graphical representation of the inhibition of cell proliferation mediated by hammerhead ribozymes targeted against sites KDR sites-527, 726 or 3950 or flt-1 site 4229. The figure also shows enhanced inhibition of cell proliferation by a combination of flt-1 and KDR hammerhead ribozymes. 4229+527, indicates the treatment of cells with both the fit 4229 and the KDR 527 ribozymes. 4229+726, indicates the treatment of cells with both the fit 4229 and the KDR 726 ribozymes. 4229+3950, indicates the treatment of cells with both the fit 4229 and the KDR 3950 ribozymes. VEGF −, indicates the basal level of cell proliferation in the absence of VEGF. A, indicates catalytically active ribozyme; I, indicates catalytically inactive ribozyme. All of these ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ termini contain phosphorothioate substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose (3′-iH).





FIG. 18

shows the inhibition of VEGF-induced angiogenesis in rat cornea mediated by anti-flt-1 hammerhead ribozyme. All of these ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 position contains 2′-C-allyl modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ termini contain phosphorothioate substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose (3′-iH). A decrease in the Surface Area corresponds to a reduction in angiogenesis. VEGF alone, corresponds to treatment of the cornea with VEGF and no ribozymes. Vehicle alone, corresponds to the treatment of the cornea with the carrier alone and no VEGF. This control gives a basal level of Surface Area. Active 4229 HH, corresponds to the treatment of cornea with the flt-1 4229 HH ribozyme in the absence of any VEGF. This control also gives a basal level of Surface Area. Active 4229 HH+VEGF, corresponds to the co-treatment of cornea with the flt-1 4229 HH ribozyme and VEGF. Inactive 4229 HH+VEGF, corresponds to the co-treatment of cornea with a catalytically inactive version of 4229 HH ribozyme and VEGF.











Ribozymes




Ribozymes of this invention block to some extent VEGF-R (specifically flt-1 and flk-1/KDR) production and can be used to treat disease or diagnose such disease. Ribozymes will be delivered to cells in culture, to cells or tissues in animal models of angiogenesis and/or RA and to human cells or tissues ex vivo or in vivo. Ribozyme cleavage of VEGF-R RNAs (specifically RNAs that encode flt-1 and flk-1/KDR) in these systems may alleviate disease symptoms.




Target Sites




Targets for useful ribozymes can be determined as disclosed in Draper et al., International PCT Publication No. WO 95/13380, and hereby incorporated by reference herein in totality. Other examples include the following PCT applications which concern inactivation of expression of disease-related genes: WO 95/23225, WO 95/13380, WO 94/02595, incorporated by reference herein. 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.




The sequence of human and mouse flt-1, KDR and/or flk-1 mRNAs were screened for optimal ribozyme target sites using a computer folding algorithm. Hammerhead or hairpin ribozyme cleavage sites were identified. These sites are shown in Tables II to IX (all sequences are 5′ to 3′ in the tables; X can be any base-paired sequence, the actual sequence is not relevant here). The nucleotide base position is noted in the Tables as that site to be cleaved by the designated type of ribozyme. While mouse and human sequences can be screened and ribozymes thereafter designed, the human targeted sequences are of most utility. However, as discussed in Stinchcomb et al., “Method and Composition for Treatment of Restenosis and Cancer Using Ribozymes,” filed May 18, 1994, U.S. Ser. No. 08/245,466, mouse targeted ribozymes may be useful to test efficacy of action of the ribozyme prior to testing in humans. The nucleotide base position is noted in the Tables as that site to be cleaved by the designated type of ribozyme.




Hammerhead or hairpin ribozymes were designed that could bind and cleave target RNA in a sequence-specific manner. The ribozymes were individually analyzed by computer folding (Jaeger et al., 1989


Proc. Natl. Acad. Sci. USA,


86, 7706) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity.




Referring to

FIG. 6

, mRNA is screened for accessible cleavage sites by the method described generally in Draper et al., PCT WO93/23569, hereby incorporated by reference herein. Briefly, DNA oligonucleotides complementary to potential hammerhead or hairpin ribozyme cleavage sites were synthesized. A polymerase chain reaction is used to generate substrates for T7 RNA polymerase transcription from human and mouse flt-1, KDR and/or flk-1 cDNA clones. Labeled RNA transcripts are synthesized in vitro from the templates. The oligonucleotides and the labeled transcripts were annealed, RNAseH was added and the mixtures were incubated for the designated times at 37° C. Reactions are stopped and RNA separated on sequencing polyacrylamide gels. The percentage of the substrate cleaved is determined by autoradiographic quantitation using a PhosphorImaging system. From these data, hammerhead or hairpin ribozyme sites are chosen as the most accessible.




Ribozymes of the hammerhead or hairpin motif were designed to anneal to various sites in the mRNA message. The binding arms are complementary to the target site sequences described above. The ribozymes were chemically synthesized. The method of synthesis used follows the procedure for normal RNA synthesis as described in Usman et al., 1987


J. Am. Chem. Soc.,


109, 7845; Scaringe et al., 1990


Nucleic Acids Res.,


18, 5433; and Wincott et al., 1995


Nucleic Acids Res.


23, 2677-2684 and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. Small scale synthesis were conducted on a 394 Applied Biosystems, Inc. synthesizer using a modified 2.5 μmol scale protocol with a 5 min coupling step for alkylsilyl protected nucleotides and 2.5 min coupling step for 2′-O-methylated nucleotides. Table XI outlines the amounts, and the contact times, of the reagents used in the synthesis cycle. A 6.5-fold excess (163 μL of 0.1 M=16.3 μmol) of phosphoramidite and a 24-fold excess of S-ethyl tetrazole (238 μL of 0.25 M=59.5 μmol) relative to polymer-bound 5′-hydroxyl was used in each coupling cycle. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, were 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer: detritylation solution was 2% TCA in methylene chloride (ABI); capping was performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); oxidation solution was 16.9 mM I


2


, 49 mM pyridine, 9% water in THF (Millipore). B & J Synthesis Grade acetonitrile was used directly from the reagent bottle. S-Ethyl tetrazole solution (0.25 M in acetonitrile) was made up from the solid obtained from American International Chemical, Inc.




Deprotection of the RNA was performed as follows. The polymer-bound oligoribonucleotide, trityl-off, was transferred from the synthesis column to a 4mL glass screw top vial and suspended in a solution of methylamine (MA) at 65° C. for 10 min. After cooling to −20 ° C., the supernatant was removed from the polymer support. The support was washed three times with 1.0 mL of EtOH:MeCN:H


2


O/3:1:1, vortexed and the supernatant was then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, were dried to a white powder.




The base-deprotected oligoribonucleotide was resuspended in anhydrous TEA.HF/NMP solution (250 μL of a solution of 1.5 mL N-methyl-pyrrolidinone, 750 μL TEA and 1.0 mL TEA.3HF to provide a 1.4M HF concentration) and heated to 65° C. for 1.5 h. The resulting, fully deprotected, oligomer was quenched with 50 mM TEAB (9 mL) prior to anion exchange desalting.




For anion exchange desalting of the deprotected oligomer, the TEAB solution was loaded onto a Qiagen 500® anion exchange cartridge (Qiagen Inc.) that was prewashed with 50 mM TEAB (10 mL). After washing the loaded cartridge with 50 mM TEAB (10 mL), the RNA was eluted with 2 M TEAB (10 mL) and dried down to a white powder.




Inactive hammerhead ribozymes were synthesized by substituting a U Hertel, K. J., et al., 1992,


Nucleic Acids Res.


20, 3252).




The average stepwise coupling yields were >98% (Wincott et al., 1995


Nucleic Acids Res.


23, 2677-2684).




Hairpin ribozymes are synthesized in two parts and annealed to reconstruct the active ribozyme (Chowrira and Burke, 1992


Nucleic Acids Res.,


20, 2835-2840). Ribozymes are also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989,


Methods Enzymol.


180, 51).




All ribozymes are modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-O-methyl, 2′-H (for a review see Usman and Cedergren, 1992


TIBS


17, 34; Usman et al., 1994


Nucleic Acids Symp. Ser.


31, 163). Ribozymes are purified by gel electrophoresis using general methods or are purified by high pressure liquid chromatography (HPLC; See Usman et al., PCT Publication No. WO95/23225, the totality of which is hereby incorporated herein by reference) and are resuspended in water.




The sequences of the ribozymes that are chemically synthesized, useful in this study, are shown in Tables II to IX. 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. Stem-loop IV sequence of hairpin ribozymes listed in for example Table III (5′-CACGUUGUG-3′) can be altered (substitution, deletion, and/or insertion) to contain any sequence, provided a minimum of two base-paired stem structure can form. The sequences listed in Tables II to IX may be formed of ribonucleotides or other nucleotides or non-nucleotides. Such ribozymes are equivalent to the ribozymes described specifically in the Tables.




Optimizing Ribozyme Activity




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 II, see

FIG. 2



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., 1990


Nature


344, 565; Pieken et al., 1991


Science


253, 314; Usman and Cedergren, 1992


Trends in Biochem. Sci.


17, 334; Usman et al., International Publication No. WO 93/15187; Rossi et al., International Publication No. WO 91/03162; Beigelman et al., 1995


J Biol Chem.


in press; as well as Sproat, U.S. Pat. No. 5,334,711 which describe various chemical modifications that can be made to the sugar moieties of enzymatic RNA molecules). Modifications which enhance their efficacy in cells, and removal of stem II bases to shorten RNA synthesis times and reduce chemical requirements are desired. (All these publications are hereby incorporated by reference herein).




Sullivan, et al., supra, describes the general methods for delivery of enzymatic RNA molecules. Ribozymes may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres. For some indications, ribozymes may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the RNA/vehicle combination is locally delivered by direct injection or by use of a catheter, infusion pump or stent. Other routes of delivery include, but are not limited to, intravascular, intramuscular, subcutaneous or joint injection, aerosol inhalation, oral (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery. More detailed descriptions of ribozyme delivery and administration are provided in Sullivan et al., supra and Draper et al., supra which have been incorporated by reference herein.




Another means of accumulating high concentrations of a ribozyme(s) within cells is to incorporate the ribozyme-encoding sequences into a DNA or RNA expression vector. Transcription of the ribozyme sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol III promoters will be expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters are also used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990


Proc. Natl. Acad. Sci. U.S.A.,


87, 6743-7; Gao and Huang 1993


Nucleic Acids Res.,


21, 2867-72; Lieber et al., 1993


Methods Enzymol.,


217, 47-66; Zhou et al., 1990


Mol. Cell. Biol.,


10, 4529≧37; Thompson et al., 1995 supra). Several investigators have demonstrated that ribozymes expressed from such promoters can function in mammalian cells (e.g. Kashani-Sabet et al., 1992


Antisense Res. Dev.,


2, 3-15;


Ojwang et al.,


1992


Proc. Natl. Acad. Sci. U.S.A.,


89,10802-6; Chen et al., 1992


Nucleic Acids Res.,


20, 4581-9; Yu et al., 1993


Proc. Natl. Acad. Sci. U.S.A,


90, 6340-4; L'Huillier et al., 1992


EMBO J.


11, 4411-8; Lisziewicz et al., 1993


Proc. Natl. Acad. Sci. U.S.A.,


90, 8000-4; Thompson et al., 1995


Nucleic Acids Res.


23, 2259). The above ribozyme transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated virus vectors), or viral RNA vectors (such as retroviral or alphavirus vectors).




In a preferred embodiment of the invention, a transcription unit expressing a ribozyme that cleaves RNAs that encode flt-1, KDR and/or flk-1 are inserted into a plasmid DNA vector or an adenovirus or adeno-associated virus DNA viral vector or a retroviral RNA vector. Viral vectors have been used to transfer genes and lead to either transient or long term gene expression (Zabner et al., 1993 Cell 75, 207; Carter, 1992


Curr. Opi. Biotech.


3, 533). The adenovirus, AAV or retroviral vector is delivered as recombinant viral particles. The DNA may be delivered alone or complexed with vehicles (as described for RNA above). The recombinant adenovirus or AAV or retroviral particles are locally administered to the site of treatment, e.g., through incubation or inhalation in vivo or by direct application to cells or tissues ex vivo. Retroviral vectors have also been used to express ribozymes in mammalian cells (Ojwang et al., 1992 supra; Thompson et al., 1995 supra).




flt-1, KDR and/or flk-1 are attractive nucleic acid-based therapeutic targets by several criteria. The interaction between VEGF and VEGF-R is well-established. Efficacy can be tested in well-defined and predictive animal models. Finally, the disease conditions are serious and current therapies are inadequate. Whereas protein-based therapies would inhibit VEGF activity nucleic acid-based therapy provides a direct and elegant approach to directly modulate flt-1, KDR and/or flk-1 expression.




Because flt-1 and KDR mRNAs are highly homologous in certain regions, some ribozyme target sites are also homologous (see Table X). In this case, a single ribozyme will target both flt-1 and KDR mRNAs. At partially homologous sites, a single ribozyme can sometimes be designed to accomodate a site on both mRNAs by including G/U basepairing. For example, if there is a G present in a ribozyme target site in KDR mRNA at the same position there is an A in the flt-1 ribozyme target site, the ribozyme can be synthesized with a U at the complementary position and it will bind both to sites. The advantage of one ribozyme that targets both VEGF-R mRNAs is clear, especially in cases where both VEGF receptors may contribute to the progression of angiogenesis in the disease state.




“Angiogenesis” refers to formation of new blood vessels which is an essential process in reproduction, development and wound repair. “Tumor ngiogenesis” refers to the induction of the growth of blood vessels from surrounding tissue into a solid tumor. Tumor growth and tumor metastasis are dependent on angiogenesis (for a review see Folkman, 1985 supra; Folkman 1990


J. Natl. Cancer Inst.,


82, 4; Folkman and Shing, 1992


J Biol. Chem.


267, 10931).




Angiogenesis plays an important role in other diseases such as arthritis wherein new blood vessels have been shown to invade the joints and degrade cartilage (Folkman and Shing, supra).




“Retinopathy” refers to inflammation of the retina and/or degenerative condition of the retina which may lead to occlusion of the retina and eventual blindness. In “diabetic retinopathy” angiogenesis causes the capillaries in the retina to invade the vitreous resulting in bleeding and blindness which is also seen in neonatal retinopathy (for a review see Folkman, 1985 supra; Folkman 1990 supra; Folkman and Shing, 1992 supra).




EXAMPLE 1




flt-1. KDR and/or flk-1 Ribozymes




By engineering ribozyme motifs applicant has designed several ribozymes directed against flt-1, KDR and/or flk-1 encoded mRNA sequences. These ribozymes were synthesized with modifications that improve their nuclease resistance (Beigelman et al., 1995


J Biol. Chem.


270, 25702) and enhance their activity in cells. The ability of ribozymes to cleave target sequences in vitro was evaluated essentially as described in Thompson et al., PCT Publication No. WO 93/23057; Draper et al., PCT Publication No. WO 95/04818.




EXAMPLE 2




Effect of Ribozymes on the Binding of VEGF to flt-1. KDR and/or flk-1 Receptors




Several common human cell lines are available that express endogenous flt-1, KDR and/or flk-1. flt-1, KDR and/or flk-1 can be detected easily with monoclonal antibodies. Use of appropriate fluorescent reagents and fluorescence-activated cell-sorting (FACS) will permit direct quantitation of surface flt-1, KDR and/or flk-1 on a cell-by-cell basis. Active ribozymes are expected to directly reduce flt-1, KDR and/or flk-1 expression and thereby reduce VEGF binding to the cells. In this example, human umbelical cord microvascular endothelial cells were used.




Cell Preparation




Plates are coated with 1.5% gelatin and allowed to stand for one hour. Cells (e.g., microvascular endothelial cells derived from human umbilical cord vein) are plated at 20,000 cells/well (24 well plate) in 200 μl growth media and incubated overnight (˜1 doubling) to yield ˜40,000 cells (75-80% confluent).




Ribozyme Treatment




Media is removed from cells and the cells are washed two times with 300 μl 1× PBS: Ca


2+


: Mg


2+


mixture. A complex of 200-500 nM ribozyme and LipofectAMINE® (3:1 lipid:phosphate ratio) in 200 μl OptiMEM® (5% FBS) was added to the cells. The cells are incubated for 6 hr (equivalent to 2-3 VEGF-R turnovers).






125


I VEGF Binding Assay




The assay is carried out on ice to inhibit internalization of VEGF during the experiment. The media containing the ribozyme is removed from the cells and the cells are washed twice with with 300 μl 1× PBS: Ca


2+


: Mg


2 +


mixture containing 1% BSA. Appropriate


125


I VEGF solution (100,000 cpm/well, +/−10× cold 1× PBS, 1% BSA) was applied to the cells. The cells are incubated on ice for 1 h.


1251


I VEGF-containing solution is removed and the cells are washed three times with with 300 μl 1× PBS: Ca


2+


: Mg


2+


mixture containing 1% BSA. To each well 300 μl of 100 mM Tris-HCl, pH 8.0, 0.5% Triton X-100 was added and the the mixture was incubated for 2 min. The


125


I VEGF-binding was quantitated using standard scintillation counting techniques.







Percent





Inhibition

=




cpm



125


|

VEGF





bound





by





the





ribozyme


-


treated





samples




cpm



125


|

VEGF





bound





by





the





Control





sample



×
100











EXAMPLE 3




Effect of Hammerhead Ribozymes Targeted Against flt-1 Receptor on the Binding of VEGF




Hammerhead ribozymes targeted to twenty sites within flt-1 RNA were synthesized as described above. Sequence of the ribozymes used are shown in Table II; the length of stem II region is 3 bp. The hammerhead ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ terminus contains phosphorothioate substitutions. Additionally, 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic ribose.




Referring to

FIG. 7

, the effect of hammerhead ribozymes targeted against flt-1 receptor on the binding of VEGF to flt-1 on the surface of human microvascular endothelial cells is shown. The majority of the ribozymes tested were able to inhibit the expression of flt-1 and thereby were able to inhibit the binding of VEGF.




In order to determine the specificity of ribozymes targeted against flt-1 RNA, the effect of five anti-flt-1 ribozymes on the binding of VEGF, UPA (urokinase plasminogen activator) and FGF (fibroblast growth factor) to their corresponding receptors were assayed. As shown in

FIG. 9

, there was significant inhibition of VEGF binding to its receptors on cells treated with anti-flt-1 ribozymes. There was no specific inhibition of the binding of UPA and FGF to their corresponding receptors. These data strongly suggest that anti-flt-1 ribozymes specifically cleave flt-1 RNA and not RNAs encoding the receptors for UPA and FGF, resulting in the inhibition of flt-1 receptor expression on the surface of the cells. Thus the ribozymes are responsible for the inhibition of VEGF binding but not the binding of UPA and FGF.




EXAMPLE 4




Effect of Hammerhead Ribozymes Targeted Against KDR Receptor on the Binding of VEGF




Hammerhead ribozymes targeted to twenty one sites within KDR RNA were synthesized as described above. Sequence of the ribozymes used are shown in Table IV; the length of stem II region is 3 bp. The hammerhead ribozymes were chemically modified such that the ribozyme consists of ribose residues at five positions; U4 and U7 positions contain 2′-NH


2


modifications, the remaining nucleotide positions contain 2′-O-methyl substitutions; four nucleotides at the 5′ terminus contains phosphorothioate substitutions. Additionally, the 3′ end of the ribozyme contains a 3′-3′ linked inverted abasic deoxyribose.




Referring to

FIG. 8

, the effect of hammerhead ribozymes targeted against KDR receptor on the binding of VEGF to KDR on the surface of human microvascular endothelial cells is shown. A majority of the ribozymes tested were able to inhibit the expression of KDR and thereby were able to inhibit the binding of VEGF. As a control, the cells were treated with a ribozyme that is not targeted towards KDR RNA (irrel. RZ); there was no specific inhibition of VEGF binding. The results from this control experiment strongly suggest that the inhibition of VEGF binding observed with anti-KDR ribozymes is a ribozyme-mediated inhibition.




EXAMPLE 5




Effect of Ribozymes Targeted Against VEGF Receptors on Cell Proliferation




Cell Preparation




24-well plates are coated with 1.5% gelatin (porcine skin 300 bloom). After 1 hr, excess gelatin is washed off of the plate. Microvascular endothelial cells are plated at 5,000 cells/well (24 well plate) in 200 μl growth media. The cells are allowed to grow for ˜18 hr (˜1 doubling) to yield ˜10,000 cells (25-30% confluent).




Ribozyme Treatment




Media is removed from the cells, and the cells are washed two times with 300 μl 1× PBS: Ca


2+


: Mg


2+


mixture.




For anti-flt-1 HH ribozyme experiment (

FIG. 12

) a complex of 500 nM ribozyme; 15 μM LFA (3:1 lipid:phosphate ratio) in 200 μl OptiMEM (5% FCS) media was added to the cells. Incubation of cells is carried out for 6 hr (equivalent to 2-3 VEGF receptor turnovers).




For anti-KDR HH ribozyme experiment (

FIG. 13

) a complex of 200 nM ribozyme; 5.25 μM LFA (3:1 lipid:phosphate ratio) in 200 μl OptiMEM (5% FCS) media was added to the cells. Incubation of cells is carried out for 3 hr.




Proliferation




After three or six hours, the media is removed from the cells and the cells are washed with 300 μl 1× PBS: Ca


2+


: Mg


2+


mixture. Maintenance media (contains dialyzed 10% FBS) +/−VEGF or basic FGF at 10 ng/ml is added to the cells. The cells are incubated for 48 or 72 h. The cells are trypsinized and counted (Coulter counter). Trypan blue is added on one well of each treatment as control.




As shown in

FIG. 12B

, VEGF and basic FGF can stimulate human microvascular endothelial cell proliferation. However, treatment of cells with 1358 HH or 4229 HH ribozymes, targeted against flt-1 mRNA, results in a significant decrease in the ability of VEGF to stimulate endothelial cell proliferation. These ribozymes do not inhibit the FGF-mediated stimulation of endothelial cell proliferation.




Human microvascular endothalial cells were also treated with hammerhead ribozymes targeted against sites 527, 730, 3702 or 3950 within the KDR mRNA. As shown in

FIG. 13

, all four ribozymes caused significant inhibition of VEGF-mediated induction of cell proliferation. No significant inhibition of cell proliferation was observed when the cells were treated with a hammerhead ribozyme targeted to an irrelevant RNA. Additionally, none of the ribozymes inhibited FGF-mediated stimulation of cell proliferation.




These results strongly suggest that hammerhead ribozymes targeted against either flt-1 or KDR mRNA can specifically inhibit VEGF-mediated induction of endothelial cell proliferation.




EXAMPLE 6




Effect of Antisense Oligonucleotides Targeted Against VEGF Receptors on Cell Proliferation (Colorimetric Assay)




Following are some of the reagents used in the proliferation assay:




Cells: Human aortic endothelial cells (HAEC) from Clonetics®. Cells at early passage are preferably used.




Uptake Medium: EBM (from Clonetics®);1% L-Glutamine;20 mM Hepes;No serum;No antibiotics.




Growth Medium: EGM (from Clonetics®);FBS to 20%;1% L-Glutamine; 20 mM Hepes.




Cell Plating: 96-well tissue culture plates are coated with 0.2% gelatin (50 μl/well). The gelatin is incubated in the wells at room temperature for 15-30 minutes. The gelatin is removed by aspiration and the wells are washed with PBS:Ca


2+


: Mg


2+


mixture. PBS mixture is left in the wells until cells are ready to be added. HAEC cells were detached by trypsin treatment and resuspended at 1.25×10


4


/ml in growth medium. PBS is removed from plates and 200 μl of cells (i.e. 2.5×10


3


cells/well) are added to each well. The cells are allowed to grow for 48 hours before the proliferation assay.




Assay: Growth medium is removed from the wells. The cells are washed twice with PBS:Ca


2+


: Mg


2+


mixture without antibiotics. A formulation of lipid/antisense oligonucleotide (antisense oligonucleotide is used here as a non-limiting example) complex is added to each well (100 μl/well) in uptake medium. The cells are incubated for 2-3 hours at 37° C. in C


2


incubator. After uptake, 100 μl/well of growth medium is added (gives final FBS concentration of 10%). After approximately 72 hours, 40 μl MTS® stock solution (made as described by manufacturer) was added to each well and incubated at 37° C. for 1-3 hours, depending on the color development. (For this assay, 2 hours was sufficient). The intensity of color formation was determined on a plate reader at 490 nM.




Phosphorothioate-substituted antisense oligodeoxynucleotides were custom synthesized by The Midland Certified Reagent Company®, Midland, Tex. Following non-limiting antisense oligodeoxynucleotides targeted against KDR RNA were used in the proliferation assay:




KDR 21 AS: 5′-GCA GCA CCT TGC TCT CCA TCC-3′




SCRAMBLED CONTROL: 5′-CTG CCA ACT TCC CAT GCC TGC-3′




As shown in

FIG. 10

, proliferation of HAEC cells are specifically inhibited by increasing concentrations of the phosphorothioate anti-KDR-antisense oligodeoxynucleotide. The scrambled antisense oligonucleotide is not expected to bind the KDR RNA and therefore is not expected to inhibit KDR expression. As expected, there is no detectable inhibition of proliferation of HAEC cells treated with a phosphorothioate antisense oligonucleotide with scrambled sequence.




EXAMPLE 7




In Vitro Cleavage of flt-1 RNA by Hammerhead Ribozymes




Referring to

FIG. 11A

, hammerhead ribozymes (HH) targeted against sites 1358 and 4229 within the flt-1 RNA were synthesized as described above.




RNA Cleavage Assay in vitro




Substrate RNA was 5′ end-labeled using [γ-


32


P] ATP and T4 polynucleotide kinase (US Biochemicals). Cleavage reactions were carried out under ribozyme “excess” conditions. Trace amount (≦1 nM) of 5′ end-labeled substrate and 40 nM unlabeled ribozyme were denatured and renatured separately by heating to 90° C. for 2 min and snap-cooling on ice for 10-15 min. The ribozyme and substrate were incubated, separately, at 37° C. for 10 min in a buffer containing 50 mM Tris-HCl and 10 mM MgCl


2


. The reaction was initiated by mixing the ribozyme and substrate solutions and incubating at 37° C. Aliquots of 5 μl are taken at regular intervals of time and the reaction is quenched by mixing with equal volume of 2× formamide stop mix. The samples are resolved on 20 % denaturing polyacrylamide gels. The results were quantified and percentage of target RNA cleaved is plotted as a function of time.




Referring to

FIG. 11B and 11C

, hammerhead ribozymes targeted against sites 1358 and 4229 within the flt-1 RNA are capable of cleaving target RNA efficiently in vitro.




EXAMPLE 8




In Vitro Cleavage of KDR RNA by Hammerhead Ribozymes




In this non-limiting example, hammerhead ribozymes targeted against sites 726, 527, 3702 and 3950 within KDR RNA were synthesized as described above. RNA cleavage reactions were carried out in vitro essentially as described under Example 7.




Referring to

FIGS. 14 and 15

, all four ribozymes were able to cleave their cognate target RNA efficiently in a sequence-specific manner.




EXAMPLE 9




In Vitro Cleavage of RNA by Hammerhead Ribozymes Targeted Against Cleavage Sites that are Homologous Between KDR and flt-1 mRNA




Because flt-1 and KDR mRNAs are highly homologous in certain regions, some ribozyme target sites are also homologous (see Table X). In this case, a single ribozyme will target both flt-1 and KDR mRNAs. Hammerhead ribozyme (FLT/KDR-I) targeted against one of the homologous sites between flt-1 and KDR (flt-1 site 3388 and KDR site 3151) was synthesized as described above. Ribozymes with either a 3 bp stem II or a 4 bp stem II were synthesized. RNA cleavage reactions were carried out in vitro essentially as described under Example 7.




Referring to

FIG. 16

, FLT/KDR-I ribozyme with either a 3 or a 4 bp stem II was able to cleave its target RNA efficiently in vitro.




EXAMPLE 10




Effect of Multiple Ribozymes Targeted Against Both flt-1 and KDR RNA on Cell Proliferation




Since both flt-1 and KDR receptors of VEGF are involved in angiogenesis, the inhibition of the expression of both of these genes may be an effective approach to inhibit angiogenesis.




Human microvascular endothalial cells were treated with hammerhead ribozymes targeted against sites flt-1 4229 alone, KDR 527 alone, KDR 726 alone, KDR 3950 alone, flt-1 4229+KDR 527, flt-1 4229+KDR 726 or flt-1 4229+KDR 3950. As shown in

FIG. 17

, all the combinations of active ribozymes (A) caused significant inhibition of VEGF-mediated induction of cell proliferation. No significant inhibition of cell proliferation was observed when the cells were treated with a catalytically inactive (I) hammerhead ribozymes. Additionally, cells treated with ribozymes targeted against both flt-i and KDR RNAs- flt-1 4229+KDR 527; flt-1 4229+KDR 726; flt-1 4229+KDR 3950, were able to cause a greater inhibition of VEGF-mediated induction of cell proliferation when compared with individual ribozymes targeted against either flt-1 or KDR RNA (see flt-1 4229 alone; KDR 527 alone; KDR 726 alone; KDR 3950 alone). This strongly suggests that treatment of cells with multiple ribozymes may be a more effective means of inhibition of gene expression.




Animal Models




There are several animal models in which the anti-angiogenesis effect of nucleic acids of the present invention, such as ribozymes, directed against VEGF-R mRNAs can be tested. Typically a corneal model has been used to study angiogenesis in rat and rabbit since recruitment of vessels can easily be followed in this normally avascular tissue (Pandey et al., 1995


Science


268: 567-569). In these models, a small Teflon or Hydron disk pretreated with an angiogenesis factor (e.g. bFGF or VEGF) is inserted into a pocket surgically created in the cornea. Angiogenesis is monitored 3 to 5 days later. Ribozymes directed against VEGF-R mRNAs would be delivered in the disk as well, or dropwise to the eye over the time course of the experiment. In another eye model, hypoxia has been shown to cause both increased expression of VEGF and neovascularization in the retina (Pierce et al., 1995


Proc. Natl. Acad. Sci. USA.


92: 905-909; Shweiki et al., 1992


J. Clin. Invest,


91: 2235-2243).




In human glioblastomas, it has been shown that VEGF is at least partially responsible for tumor angiogenesis (Plate et al., 1992


Nature


359, 845). Animal models have been developed in which glioblastoma cells are implanted subcutaneously into nude mice and the progress of tumor growth and angiogenesism is studied (Kim et al., 1993 supra; Millauer et al., 1994 supra).




Another animal model that addresses neovascularization involves Matrigel, an extract of basement membrane that becomes a solid gel when injected subcutaneously (Passaniti et al., 1992


Lab. Invest.


67: 519-528). When the Matrigel is supplemented with angiogenesis factors such as VEGF, vessels grow into the Matrigel over a period of 3 to 5 days and angiogenesis can be assessed. Again, ribozymes directed against VEGF-R mRNAs would be delivered in the Matrigel.




Several animal models exist for screening of anti-angiogenic agents. These include corneal vessel formation following corneal injury (Burger et al., 1985 Cornea 4: 35-41; Lepri, et al., 1994


J. Ocular Pharmacol.


10: 273-280; Ormerod et al., 1990


Am. J. Pathol.


137: 1243-1252) or intracorneal growth factor implant (Grant et al., 1993


Diabetologia


36: 282-291; Pandey et al. 1995 supra; Zieche et al., 1992


Lab. Invest


67: 711-715), vessel growth into Matrigel matrix containing growth factors (Passaniti et al., 1992 supra), female reproductive organ neovascularization following hormonal manipulation (Shweiki et al., 1993


Clin. Invest.


91: 2235-2243), several models involving inhibition of tumor growth in highly vascularized solid tumors (O'Reilly et al., 1994


Cell


79: 315-328; Senger et al., 1993


Cancer and Metas. Rev.


12: 303-324; Takahasi et al., 1994


Cancer Res.


54: 4233-4237; Kim et al., 1993 supra), and transient hypoxia-induced neovascularization in the mouse retina (Pierce et al., 1995


Proc. Natl. Acad. Sci. USA.


92: 905-909).




The cornea model, described in Pandey et al. supra, is the most common and well characterized anti-angiogenic agent efficacy screening model. This model involves an avascular tissue into which vessels are recruited by a stimulating agent (growth factor, thermal or alkalai burn, endotoxin). The corneal model would utilize the intrastromal corneal implantation of a Teflon pellet soaked in a VEGF-Hydron solution to recruit blood vessels toward the pellet which can be quantitated using standard microscopic and image analysis techniques. To evaluate their anti-angiogenic efficacy, ribozymes are applied topically to the eye or bound within Hydron on the Teflon pellet itself. This avascular cornea as well as the Matrigel (see below) provide for low background assays. While the corneal model has been performed extensively in the rabbit, studies in the rat have also been conducted.




The mouse model (Passaniti et al., supra) is a non-tissue model which utilizes Matrigel, an extract of basement membrane (Kleinman et al., 1986) or Millipore® filter disk, which can be impregnated with growth factors and anti-angiogenic agents in a liquid form prior to injection. Upon subcutaneous administration at body temperature, the Matrigel or Millipore® filter disk forms a solid implant. VEGF embedded in the Matrigel or Millipore® filter disk would be used to recruit vessels within the matrix of the Matrigel or Millipore® filter disk which can be processed histologically for endothelial cell specific vWF (factor VIII antigen) immunohistochemistry, Trichrome-Masson stain, or hemoglobin content. Like the cornea, the Matrigel or Millipore® filter disk are avascular; however, it is not tissue. In the Matrigel or Millipore® filter disk model, ribozymes are administered within the matrix of the Matrigel or Millipore® filter disk to test their anti-angiogenic efficacy. Thus, delivery issues in this model, as with delivery of ribozymes by Hydron- coated Teflon pellets in the rat cornea model, may be less problematic due to the homogeneous presence of the ribozyme within the respective matrix.




These models offer a distinct advantage over several other angiogenic models listed previously. The ability to use VEGF as a pro-angiogenic stimulus in both models is highly desirable since ribozymes will target only VEGFr mRNA. In other words, the involvement of other non-specific types of stimuli in the cornea and Matrigel models is not advantageous from the standpoint of understanding the pharmacologic mechanism by which the anti-VEGFr mRNA ribozymes produce their effects. In addition, the models will allow for testing the specificity of the anti-VEGFr mRNA ribozymes by using either a- or bFGF as a pro-angiogenic factor. Vessel recruitment using FGF should not be affected in either model by anti-VEGFr mRNA ribozymes. Other models of angiogenesis including vessel formation in the female reproductive system using hormonal manipulation (Shweiki et al., 1993 supra); a variety of vascular solid tumor models which involve indirect correltations with angiogenesis (O'Reilly et al., 1994 supra; Senger et al., 1993 supra; Takahasi et al., 1994 supra; Kim et al., 1993 supra); and retinal neovascularization following transient hypoxia (Pierce et al., 1995 supra) were not selected for efficacy screening due to their non-specific nature, although there is a correlation between VEGF and angiogenesis in these models.




Other model systems to study tumor angiogenesis is reviewed by Folkman, 1985 Adv. Cancer. Res. 43,175.




flt-1, KDR and/or flk-1 protein levels can be measured clinically or experimentally by FACS analysis. flt-1, KDR and/or flk-1 encoded mRNA levels will be assessed by Northern analysis, RNase-protection, primer extension analysis and/or quantitative RT-PCR. Ribozymes that block flt-1, KDR and/or flk-1 protein encoding mRNAs and therefore result in decreased levels of flt-1, KDR and/or flk-1 activity by more than 20% in vitro will be identified.




Ribozymes and/or genes encoding them are delivered by either free delivery, liposome delivery, cationic lipid delivery, adeno-associated virus vector delivery, adenovirus vector delivery, retrovirus vector delivery or plasmid vector delivery in these animal model experiments (see above).




Patients can be treated by locally administering nucleic acids targeted against VEGF-R by direct injection. Routes of administration may include, but are not limited to, intravascular, intramuscular, subcutaneous, intraarticular, aerosol inhalation, oral (tablet, capsule or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery.




EXAMPLE 11




Ribozyme-mediated Inhibition of Angiogenesis in vivo




The purpose ot this study was to assess the anti-angiogenic activity of hammerhead ribozymes targeted against flt-1 4229 site in the rat cornea model of VEGF induced angiogenesis (see above). These ribozymes have either active or inactive catalytic core and either bind and cleave or just bind to VEGF-R mRNA of the flt-1 subtype. The active ribozymes, that are able to bind and cleave the target RNA, have been shown to inhibit (


125


I-labeled) VEGF binding in cultured endothelial cells and produce a dose-dependent decrease in VEGF induced endothelial cell proliferation in these cells (see Examples 3-5 above). The catalytically inactive forms of these ribozymes, wherein the ribozymes can only bind to the RNA but cannot catalyze RNA cleavage, fail to show these characteristics. The ribozymes and VEGF were co-delivered using the filter disk method: Nitrocellulose filter disks (Millipore®) of 0.057 diameter were immersed in appropriate solutions and were surgically implanted in rat cornea as described by Pandey et al., supra. This delivery method has been shown to deliver rhodamine-labeled free ribozyme to scleral cells and, in all likelihood cells of the pericorneal vascular plexus. Since the active ribozymes show cell culture efficacy and can be delivered to the target site using the disk method, it is essential that these ribozymes be assessed for in vivo anti-angiogenic activity.




The stimulus for angiogenesis in this study was the treatment of the filter disk with 30 μM VEGF which is implanted within the cornea's stroma. This dose yields reproducible neovascularization stemming from the pericorneal vascular plexus growing toward the disk in a dose-response study 5 days following implant. Filter disks treated only with the vehicle for VEGF show no angiogenic response. The ribozymes was co-adminstered with VEGF on a disk in two different ribozyme concentrations. One concern with the simultaneous administration is that the ribozymes will not be able to inhibit angiogenesis since VEGF receptors can be stimulated. However, we have observed that in low VEGF doses, the neovascular response reverts to normal suggesting that the VEGF stimulus is essential for maintaining the angiogenic response. Blocking the production of VEGF receptors using simultaneous administration of anti-VEGF-R mRNA ribozymes could attenuate the normal neovascularization induced by the filter disk treated with VEGF.




Materials and Methods:




Stock hammerhead ribozyme solutions




a. flt-1 4229 (786 μM)- Active




b. flt-1 4229 (736 μM)- Inactive




2. Experimantal Solutions/groups




Group 1 Solution 1 Control VEGF solution: 30 μM in 82 mM Tris base




Group 2 Solution 2 flt-1 4229 (1 μg/μL) in 30 μM VEGF/82 mM Tris base




Group 3 Solution 3 flt-1 4229 (10 μg/μL) in 30 μM VEGF/82 mM Tris base




Group 4 Solution 4 No VEGF, flt-1 4229 (10 μg/μL) in 82 mM Tris base




Group 5 Solution 5 No VEGF, No ribozyme in 82 mM Tris base




10 eyes per group, 5 animals (Since they have similar molecular weights, the molar concentrations should be essentially similar).




Each solution (VEGF and RIBOZYMES) were prepared as a 2× solution for 1:1 mixing for final concentrations above, with the exception of solution 1 in which VEGF was 2× and diluted with ribozyme diluent (sterile water).




3. VEGF Solutions




The 2× VEGF solution (60 μM) was prepared from a stock of 0.82 μg/μL in 50 mM Tris base. 200 μL of VEGF stock was concentrated by speed vac to a final volume of 60.8 μL, for a final concentration of 2.7 μg/μL or 60 μM. Six 10 μL aliquots was prepared for daily mixing. 2× solutions for VEGF and Ribozyme was stored at 4° C. until the day of the surgery. Solutions were mixed for each day of surgery. Original 2× solutions was prepared on the day before the first day of the surgery.




4. Surgical Solutions




Anesthesia




stock ketamine hydrochloride 100 mg/mL




stock xylazine hydrochloride 20 mg/mL




stock acepromazine 10 mg/mL




Final anesthesia solution: 50 mg/mL ketamine, 10 mg/mL xylazine, and 0.5 mg/mL acepromazine




5% povidone iodine for opthalmic surgical wash 2% lidocaine (sterile) for opthalmic administration (2 drops per eye)




sterile 0.9% NaCl for opthalmic irrigation




5. Surgical Methods




Standard surgical procedure as described in Pandey et al., supra. Filter disks were incubated in 1 μL of each solution for approximately 30 minutes prior to implantation.




5. Experimental Protocol




The animal cornea were treated with the treatment groups as described above. Animals were allowed to recover for 5 days after treatment with daily observation (scoring 0-3). On the fifth day animals were euthanized and digital images of each eye was obtained for quantitaion using Image Pro Plus. Quantitated neovascular surface area were analyzed by ANOVA followed by two post-hoc tests including Dunnets and Tukey-Kramer tests for significance at the 95% confidence level. Dunnets provide information on the significance between the differences within the means of treatments vs. controls while Tukey-Kramer provide information on the significance of differences within the means of each group.




Results are graphically represented in FIG.


18


. As shown in the figure, flt-1 4229 active hammerhead ribozyme at both concentrations was effective at inhibiting angiogenesis while the inactive ribozyme did not show any significant reduction in angiogenesis. A statistically signifiant reduction in neovascular surface area was observed only with active ribozymes. This result clearly shows that the ribozymes are capable of significantly inhibiting angiogenesis in vivo. Specifically, the mechanism of inhibition appears to be by the binding and cleavage of target RNA by ribozymes.




Diagnostic Uses




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




In a specific example, ribozymes which can cleave only wild-type or mutant forms of the target RNA are used for the assay. The first ribozyme is used to identify wild-type RNA present in the sample and the second ribozyme will be used to identify mutant RNA in the sample. As reaction controls, synthetic substrates of both wild-type and mutant RNA will be cleaved by both ribozymes to demonstrate the relative ribozyme efficiencies in the reactions and the absence of cleavage of the “non-targeted” RNA species. The cleavage products from the synthetic substrates will also serve to generate size markers for the analysis of wild-type and mutant RNAs in the sample population. Thus each analysis will require two ribozymes, two substrates and one unknown sample which will be combined into six reactions. The presence of cleavage products will be determined using an RNAse protection assay so that full-length and cleavage fragments of each RNA can be analyzed in one lane of a polyacrylamide gel. It is not absolutely required to quantify the results to gain insight into the expression of mutant RNAs and putative risk of the desired phenotypic changes in target cells. The expression of mRNA whose protein product is implicated in the development of the phenotype (i.e., flt-1, KDR and/or flk-1) 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.












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 4-16 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 RN (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 of nucleotides on both sides of the






cleavage site.






14 known members of this class. Found in a number of plant






pathogens (virusoids) that use RNA as the infectious agent (FIG.






1 and 2)






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 of 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).






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











Human fltl VEGF Receptor-Hammerhead Ribozyme and






Substrate Sequence













nt.








Position




HH Ribozyme




Substrate









  10




GCCGAGAG CUGAUGA X GAA AGUGUCCG




CGGACACUC CUCUCGGC













  13




GGAGCCGA CUGAUGA X GAA AGGAGUGU




ACACUCCUC UCGGCUCC













  15




GAGGAGCC CUGAUGA X GAA AGAGGAGU




ACUCCUCUC GGCUCCUC













  20




CCGGGGAG CUGAUGA X GAA AGCCGAGA




UCUCGGCUC CUCCCCGG













  23




CUGCCGGG CUGAUGA X GAA AGGAGCCG




CGCCUCCUC CCCGGCAG













  43




CCCGCCCC CUGAUGA X GAA AGCCGCCG




CGGCGGCUC GGAGCGGG













  54




GAGCCCCG CUGAUGA X GAA AGCCCGCU




AGCGGGCUC CGGGGCUC













  62




CUGCACCC CUGAUGA X GAA AGCCCCGG




CCGGGGCUC GGGUGCGG













  97




CCCCGGGU CUGAUGA X GAA AUCCUCGC




GCGAGGAUU ACCCGGGG













  98




UCCCCGGG CUGAUGA X GAA AAUCCUGG




CGAGGAUUA CCCGGGGA













 113




CAGGAGAC CUGAUGA X GAA ACCACUUC




GAAGUGGUU GUCUCCUG













 116




AGCCAGGA CUGAUGA X GAA ACAACCAC




GUGGUUGUC UCCUGGCU













 118




CCAGCCAG CUGAUGA X GAA AGACAACC




GGUUGUCUC CUGGCUGG













 145




CGCGCCCU CUGAUGA X GAA AGCGCCCG




CGGGCGCUC AGGGCGCG













 185




GGCCGCCA CUGAUGA X GAA AGUCCGUC




GACGGACUC UGGCGGCC













 198




CGGCCAAC CUGAUGA X GAA ACCCGGCC




GGCCGGGUC GUUGGCCG













 201




CCCCGGCC CUGAUGA X GAA ACGACCCG




CGGGUCGUU GGCCGGGG













 240




GUGAGCGC CUGAUGA X GAA ACGCGGCC




GGCCGCGUC GCGCUCAC













 246




ACCAUGGU CUGAUGA X GAA AGCGCGAC




GUCGCGCUC ACCAUGGU













 255




CAGUAGCU CUGAUGA X GAA ACCAUGGU




ACCAUGGUC AGCUACUG













 260




UGUCCCAG CUGAUGA X GAA AGCUCACC




GGUCAGCUA CUGGGACA













 276




CACAGCAG CUGAUGA X GAA ACCCCGGU




ACCGGGGUC CUGCUGUG













 294




ACACAGCU CUGAUGA X GAA AGCAGCGC




GCGCUGCUC AGCUGUCU













 301




GAGAAGCA CUGAUGA X GAA ACAGCUGA




UCAGCUGUC UGCUUCUC













 306




CCUGUGAG CUGAUGA X GAA AGCAGACA




UGUCUGCUU CUCACAGG













 307




UCCUGUGA CUGAUGA X GAA AAGCAGAC




GUCUGCUUC UCACAGGA













 309




GAUCCUGU CUGAUGA X GAA AGAAGCAG




CUGCUUCUC ACAGGAUC













 317




CUGAACUA CUGAUGA X GAA AUCCUGUG




CACAGGAUC UUGUUCAG













 319




ACCUGAAC CUGAUGA X GAA AGAUCCUG




CAGGAUCUA GUUCAGGU













 322




UGAACCUG CUGAUGA X GAA ACUAGAUC




GAUCUAGUU CAGGUUCA













 323




UUGAACCU CUGAUGA X GAA AACUAGAU




AUCUAGUUC AGGUUCAA













 328




UAAUUUUG CUGAUGA X GAA ACCUGAAC




GUUCAGGUU CAAAAUUA













 329




UUAAUUUU CUGAUGA X GAA AACCUGAA




UUCAGGUUC AAAAUUAA













 335




GAUCUUUU CUGAUGA X GAA AUUUUGAA




UUCAAAAUU AAAAGAUC













 336




GGAUCUUU CUGAUGA X GAA AAUUUUGA




UCAAAAUUA AAAGACCC













 343




CAGUUCAG CUGAUGA X GAA AUCUUUUA




UAAAAGAUC CUGAACUG













 355




GCCUUUUA CUGAUGA X GAA ACUCAGUU




AACUGAGUU UAAAAGGC













 356




UGCCUUUU CUGAUGA X GAA AACAGAGU




ACUGAGUUU AAAAGGCA













 357




GGCCCUUU CUGAUGA X GAA AAACUCAG




CUGAGUUUA AAAGGCAC













 375




GCUUGCAU CUGAUGA X GAA AUGUGCUG




CAGCACAUC AUGCAACC













 400




GCAUUGGA CUGAUGA X GAA AUGCAGUG




CACUCCAUC UCCAAUGC













 402




CUGCAUUG CUGAUGA X GAA AGAUGCAG




CUGCAUCUC CAAUGCAG













 427




AGACCAUU CUGAUGA X GAA AUGGGCUG




CAGCCCAUA AAUGGUCU













 434




CAGGCAAA CUGAUGA X GAA ACCAUUUA




UAAAUGGUC UUUGCCUG













 436




UUCAGGCA CUGAUGA X GAA ACACCAUU




AAUGGUCUU UGCCUGAA













 437




UUUCAGGC CUGAUGA X GAA AAGAUCAU




AUGGUCUUU GCCUGAAA













 454




GCUUUCCU CUGAUGA X GAA ACUCACCA




UGGUGAGUA AGGAAAGC













 477




GAUUUAGU CUGAUGA X GAA AUGCUCAG




CUGAGCAUA ACUAAAUC













 481




GGCAGAUU CUGAUGA X GAA AGUUAUGC




GCAUAACUA AAUCUGCC













 485




CACAGGCA CUGAUGA X GAA AUUUAGUU




AACUAAAUC UGCCUGUG













 512




UACUGCAG CUGAUGA X GAA AUUGUUUG




CAAACAAUU CUGCAGUA













 513




GUACUGCA CUGAUGA X GAA AAUUGUUU




AAACAAUUC UGCAGGAC













 520




GGUUAAAG CUGAUGA X GAA ACUGCAGA




UCUGCAGUA CUUUAACC













 523




CAAGGUUA CUGAUGA X GAA AGUACUGC




GCAGUACUU UAACCUUG













 524




UCAAGGUU CUGAUGA X GAA AAGUACUG




CAGUACUUU AACCUUGA













 525




UUCAAGGU CUGAUGA X GAA AAAGUACU




AGUACUUUA ACCUUGAA













 530




CUGUGUUC CUGAUGA X GAA AGGUUAAA




UUUAACCUU GAACACCG













 541




GUUUGCUU CUGAUGA X GAA AGCUCUGU




ACACAGCUC AAGCAAAC













 560




AGCUGUAG CUGAUGA X GAA AGCCAGUG




CACUGGCUU CUACAGCU













 561




CAGCUGUA CUGAUGA X GAA AAGCCAGU




ACUGGCUUC UACAGCUG













 563




UGCAGCUG CUGAUGA X GAA AGAAGCCA




UGGCUUCUA CAGCUGCA













 575




CAGCUAGA CUGAUGA X GAA AUUUGCAG




CUUCAAAUA UCCAGCUG













 577




UACAGCUA CUGAUGA X GAA AUAUUUGC




GCAAAUAUC UAGCUGUA













 579




GGUACAGC CUGAUGA X GAA AGAUAUUU




AAAUAUCUA GCUGUACC













 585




GAAGUGGG CUGAUGA X GAA ACAGCCAG




CUAGCUGUA CCUACUUC













 589




CUUUGAAG CUGAUGA X GAA AGGUACAG




CUGUACCUA CUUCAAAG













 592




CUUCUUUG CUGAUGA X GAA AGUAGGUA




UACCUACUU CAAAGAAG













 593




UCUUCUUU CUGAUGA X GAA AAGGAGGU




ACCUACUUC AAAGAAGA













 614




AGAUUGCA CUGAUGA X GAA AUUCUGUU




AACAGAAUC UGCAAUCU













 621




AAUAUAUA CUGAUGA X GAA AUUGCAGA




UCUGCAAUC UAUAUAUU













 623




UAAAUAUA CUGAUGA X GAA AGAUUGCA




UGCAAUCUA UUUAUUUA













 625




AAUAAAUA CUGAUGA X GAA AUAGAUUG




CAAUCUAUA UAUUUAUU













 627




CUAAUAAA CUGAUGA X GAA AUAUAGAU




AUCUAUAUA UUUAUUAG













 629




CACUAAUA CUGAUGA X GAA AUAUAUAG




CUAUAUAUU UUUUACUG













 630




UCACUAAU CUGAUGA X GAA AAUAUAUA




UAUAUAUUU AUUAGUGA













 631




ACCACUAA CUGAUGA X GAA AAAUAUAU




AUAUAUUUA UUAGUGAU













 633




GUAUCACU CUGAUGA X GAA AUAAAUAU




AUAUUUAUU AGUGAUAC













 634




UGUAUCAC CUGAUGA X GAA AAUAAAUA




UAUUUAUUA GUGAUACA













 640




UCUACCUG CUGAUGA X GAA AUCACUAA




UUAGUGAUA CAGGUAGA













 646




GAAAGGUC CUGAUGA X GAA ACCUGUAU




AUACAGGUA GACCUUUC













 652




CUCUACGA CUGAUGA X GAA AGGUCUAC




GUAGACCUU UCGUAGAG













 653




UCUCUCUG CUGAUGA X GAA AAGGUCUA




UAGACCUUU CGUAGAGA













 654




AUCUCUAC CUGAUGA X GAA AAAGGUCU




AGACCUUUC GUAGAGAU













 657




UACAUCUC CUGAUGA X GAA ACGAAAGG




CCUUUCGUA GAGAUGUA













 665




UUUCACUG CUGAUGA X GAA ACAUCUCU




AGAGAUGUA CAGUGAAA













 675




AUUUCGGG CUGAUGA X GAA AUUUCACU




AGUGAAAUC CCCGAAAU













 684




AGGUGUAU CUGAUGA X GAA AUUUGGGG




CCCGAAAUU AUACACAU













 685




CAUGUGUA CUGAUGA X GAA AAUUUCGG




CCGAAAUUA UACACAUG













 687




GUCAUGUG CUGAUGA X GAA AUAAUUUC




GAAAUUUUA CACAUGAC













 711




GGAAUGAC CUGAUGA X GAA AGCUCCCU




AGGGAGCUC GUCAUUCC













 714




CAGGGAAU CUGAUGA X GAA ACGAGCUC




GAGCUCGUC AUUCCCUG













 717




CGGCAGGG CUGAUGA X GAA AUGACGAG




CUCGUCAUU CCCUGCCG













 718




CCGGCAGG CUGAUGA X GAA AAUGACGA




UCGUCAUUC CCUGCCGG













 729




GGUGACCU CUGAUGA X GAA ACCCGGCA




UGCCGGGUU ACGUCACC













 730




AGGUGACG CUGAUGA X GAA AACCCGGC




GCCGGGUUA CGUCACCU













 734




UGUUAGGU CUGAUGA X GAA ACGUAACC




GGUUACGUC ACCUAACA













 739




AGUGAUGU CUGAUGA X GAA AGGUGACG




CGUCACCUA ACAUCACU













 744




GUAACAGU CUGAUGA X GAA AUGUUAGG




CCUAACAUC ACUGUUAC













 750




UUUAAAGU CUGAUGA X GAA ACAGUGAU




AUCACUGUU ACUUUAAA













 751




UUUUAAAG CUGAUGA X GAA AACAGUGA




UCACUGUUA CUUUAAAA













 754




CUUUUUUA CUGAUGA X GAA ACUAACAG




CUGUUACUU UAAAAAAG













 755




ACUUUUUU CUGAUGA X GAA AAGUAACA




UGUUACUUU AAAAAAGU













 756




AACUUUUU CUGAUGA X GAA AAAGUAAC




GUUACUUUA AAAAAGUU













 764




CAAGUGGA CUGAUGA X GAA ACUUUUUU




AAAAAAGUU UCCACUUG













 765




UCAAGUGG CUGAUGA X GAA AACUUUUU




AAAAAGUUU CCACUGGA













 766




GUCAAGUG CUGAUGA X GAA AAACUUUU




AAAAGUUUC CACUUGAC













 771




AAAGUGUC CUGAUGA X GAA AGUGGAAA




UUUCCACUU GACACUUU













 778




AGGGAUCA CUGAUGA X GAA AGUGUCAA




UUGACACUU UGAUCCCU













 779




CAGGGCUC CUGAUGA X GAA AAGUGUCA




UGACACUUU GAUCCCUG













 783




CCAUCAGG CUGAUGA X GAA AYCAAAGU




ACUUUGAUC CCUGAUGG













 801




UCCCAGAU CUGAUGA X GAA AUGCGUUU




AAACGCAUA AUCUGGGA













 804




CUGUCCCA CUGAUGA X GAA AUUAUCUG




CGCAUAAUC UGGGACAG













 814




GCCCUUUC CUGAUGA X GAA ACUGUCCC




GGGACAGUA GAAAGGGC













 824




AUAUGAUG CUGAUGA X GAA AGCCCUUU




AAAGGGCUU CAUCAUAU













 825




GAUAUGAU CUGAUGA X GAA AAGCCCUU




AAGGGCUUC AACAUAUC













 828




UUUGAUAU CUGAUGA X GAA AUGAAGCC




GGCUUCAUC AUAUCAAA













 831




GCAUUUGA CUGAUGA X GAA AUGAUGAA




UUCAUUCUA UCAAAUGC













 833




UUGCAUUU CUGAUGA X GAA AUAUGAUG




CAUCAUAUC AAAUGCAA













 845




UUUCUUUG CUGAUGA X GAA ACGUUGCA




UGCAACGUA CAAAGAAA













 855




AGAACCCC CUGAUGA X GAA AUUUCUUU




AAAGAAAUA GGGCUUCU













 861




CAGGUCAG CUGAUGA X GAA AGCCCUAU




AUAGGGCUU CUGACCUG













 862




ACAGGUCA CUGAUGA X GAA AAGCCCUA




UAGGGCUUC UGACCUGU













 882




UGCCCAUU CUGAUGA X GAA ACUGUUGC




GCAACAGUC AAUGGGCA













 892




CUUAUACA CUGAUGA X GAA AUGCCCAU




AUGGGCAUU UGUAUAAG













 893




UCUUAUAC CUGAUGA X GAA AAUGCCCA




UGGGCAUUU GUAUAAGA













 896




UUGUCUUA CUGAUGA X GAA ACAAAUGC




GCAUUUGUA UAAGACAA













 898




GUUUGUCU CUGAUGA X GAA AUACAAAU




AUUUGUAUA AGACAAAC













 908




GUGUGAGA CUGAUGA X GAA AGUUUGUC




GACAAACUA UCUCACAC













 910




AUGUGUGA CUGAUGA X GAA AUAGUUUG




CAAACUAUC UCACACAU













 912




CGAUGUGU CUGAUGA X GAA AGAUAGUU




AACUAUCUC ACACAUCG













 919




GGUUUGUC CUGAUGA X GAA AUGUGUGA




UCACACAUC GACAAACC













 931




UAUGAUUG CUGAUGA X GAA AUUGGUUU




AAACCAAUA CAAUCAUA













 936




ACAUCUAU CUGAUGA X GAA AUUGUAUU




AAUACAAUC AUAGAUGU













 939




UGGACAUC CUGAUGA X GAA AUGAUUGU




ACAAUCAUA GAUGUCCA













 945




CUUAUUUG CUGAUGA X GAA ACAUCUAU




AUAGAUGUC CAAAUAAG













 951




GGUGUGCU CUGAUGA X GAA AUUUGGAC




GUCCAAAUA AGCACACC













 969




AGUAAUUU CUGAUGA X GAA ACUGGGCG




CGCCCAGUC AAAUUACU













 974




CUCUAAGU CUGAUGA X GAA AUUUGACU




AGUCAAAUU ACUUAGAG













 975




CCUCUAAG CUGAUGA X GAA AAUUUGAC




GUCAAAUUA CUUAGAGG













 978




UGGCCUCU CUGAUGA X GAA AGUAAUUU




AAAUUACUU AGAGGCCA













 979




AUGGCCUC CUGAUGA X GAA AAGUAAUU




AAUUACUUA GAGGCCAU













 988




GACAAGAG CUGAUGA X GAA AUGGCCUC




GAGGCCAUA CUCUUGUC













 991




GAGGACAA CUGAUGA X GAA AGUAUGGC




GCCAUACUC UUGUCCUC













 993




UUGAGGAC CUGAUGA X GAA AGAGUAUG




CAUACUCUU GUCCUCAA













 996




CAAUUGAG CUGAUGA X GAA ACAAGAGU




ACUCUUGUC CUCAAUUG













 999




GUACAAUU CUGAUGA X GAA AGGACAAG




CUUGUCCUC AAUUGUAC













1003




AGCAGGAC CUGAUGA X GAA AUUGACGA




UCCUCAAUU GUACUGCU













1006




GGGAGCAG CUGAUGA X GAA ACAAUUGA




UCAAUUGUA CUGCUACC













1012




GGGAGUGG CUGAUGA X GAA AGCAGUAC




GUACUGCUA CCACUCCC













1018




GUUCAAGG CUGAUGA X GAA AGUGGUAG




CUACCACUC CCUUGAAC













1022




UCGUGUUC CUGAUGA X GAA AGGGAGUG




CACUCCCUU GAACACGA













1035




GUCAUUUG CUGAUGA X GAA ACUCUCGU




ACGAGAGUU CAAAUGAC













1036




GGUCAUUU CUGAUGA X GAA AACUCUCG




CGAGAGUUC AAAUGACC













1051




AUCAGGGU CUGAUGA X GAA ACUCCAGG




CCUGGAGUU ACCCUGAU













1052




CAUCAGGG CUGAUGA X GAA AACUCCAG




CUGGAGUUA CCCUGAUG













1069




AGCUCUCU CUGAUGA X GAA AUUUUUUU




AAAAAAAUA AGAGAGCU













1078




CCCUACGG CUGAUGA X GAA AGCUCUCU




AGAGAGCUU CCGUAAGG













1079




GCCUUACG CUGAUGA X GAA AAGCUCUC




GAGAGCUUC CGUAAGGC













1083




CGUCGCCU CUGAUGA X GAA ACGGAAGC




GCUUCCGUA AGGCGACG













1095




CUUUGGUC CUGAUGA X GAA AUUCGUCG




CGACGAAUU GACCAAAG













1108




GGCAUGGG CUGAUGA X GAA AUUGCUUU




AAAGCAAUU CCCAUGCC













1109




UGGCAUGG CUGAUGA X GAA AAUUGCUU




AAGCAAUUC CCAUGCCA













1122




CUGUAGAA CUGAUGA X GAA AUGUUGGC




GCCAACAUA UUCUACAG













1124




CACUGUAG CUGAUGA X GAA AUUUGUUG




CAACAUAUU CUACAGUG













1125




ACACUGUA CUGAUGA X GAA AAUAUAUU




AACAUAUUC UACAGUGU













1127




GAACACUG CUGAUGA X GAA AGAAUAUG




CAUAUUCUA CAGUGUUC













1134




AUAGUAAG CUGAUGA X GAA ACACUGUA




UACAGUGUU CUUACUAU













1135




AAUAGUAA CUGAUGA X GAA AACACUGU




ACAGUGUUC UUACUAUU













1137




UCAAUAGU CUGAUGA X GAA AGAACACU




AGUGUUCUU ACUAUUGA













1138




GUCAAUAG CUGAUGA X GAA AAGAACAC




GUGUUCUUA CUAUUGAC













1141




UUUGUCAA CUGAUGA X GAA ACUAAGAA




UUCUUACUA UUGACAAA













1143




AUUUUGUC CUGAUGA X GAA AUAGUAAG




CUUACUAUU GACAAAAU













1173




CAACUAUA CUGAUGA X GAA AGUCCUUU




AAAGGACUU UUUACUUG













1174




ACAAGCAU CUGAUGA X GAA AAGUCCUU




AAGGACUUU AUACUUGU













1175




GACAAGGA CUGAUGA X GAA AAAGUCCU




AGGACUUUA UACUUGUC













1177




ACGACAAG CUGAUGA X GAA AUAAAGUC




GACUUUAUA CUUGUCGU













1180




UACACGAC CUGAUGA X GAA AGUAUAAA




UUUAUACUU GUCGUGUA













1183




CCUUACAC CUGAUGA X GAA ACAAGUAU




AUACUUGUC GUGUAAGG













1188




CCACUCCU CUGAUGA X GAA ACACGACA




UGUCGUGUA AGGAGUGG













1202




AUUUGAAU CUGAUGA X GAA AUGGUCCA




UGGCUCUUC AUUCAAAU













1205




CAGAUUUG CUGAUGA X GAA AUGAUGGU




ACCAUCAUU CAAAUCUG













1206




ACAGAUUU CUGAUGA X GAA AAUGAUGG




CCAUCAUUC AAAUCUGU













1211




UGUUAACA CUGAUGA X GAA AUUUGAAU




AUUCAAAUC UGUUAACA













1215




GAGGUGUU CUGAUGA X GAA ACAGAUUU




AAAUCUGUU AACACCUC













1216




UGAGGUGU CUGAUGA X GAA AACAGAUU




AAUCUGUUA ACACCUCA













1223




UAUGCACU CUGAUGA X GAA AGGUGUGA




UAACACCUC AGUGCAUA













1231




AUCAUAUA CUGAUGA X GAA AUGGACUG




CAGUGCAUA UAUAUGAU













1233




UUAUCAUA CUGAUGA X GAA AUAUGCAC




GUGCAUAUA UAUGAUAA













1235




CUUUAUCA CUGAUGA X GAA AUAUAUGC




GCAUAUAUA UGAUAAAG













1240




GAAUGCUU CUGAUGA X GAA AUCAUAUA




UAUAUGAUA AAGCAUUC













1247




CAGUGAUG CUGAUGA X GAA AUGCUUUA




UAAAGCAUU CAUCACUG













1248




ACAGUGAU CUGAUGA X GAA AAUGCUUU




AAAGCAUUC AUAACUGU













1251




UUCACAGU CUGAUGA X GAA AUGAAUGC




GCAUUCAUC ACUGUGAA













1264




CUGUUUUC CUGAUGA X GAA AUGUUUCA




UGAAACAUC GAAAACAG













1281




ACGGUUUC CUGAUGA X GAA AGCACCUG




CAGGUGCUU GAAACCGU













1290




UUGCCAGC CUGAUGA X GAA ACGGUUUC




GAAACCGUA GCUGGCAA













1304




GCCGGUAA CUGAUGA X GAA ACCGCUUG




CAAGCGGUC UUACCGGC













1306




GAGCCGGU CUGAUGA X GAA AGACCGCU




AGCGGUCUU ACCGGCUC













1307




AGAGCCGG CUGAUGA X GAA AAGACCGC




GCGGUCUUA CCGGCUCU













1314




UUCAUAGA CUGAUGA X GAA AGCCGGUA




UACCGGCUC UCUAUGAA













1316




CUUUCAUA CUGAUGA X GAA AGAGCCGG




CCGGCUCUC UAUGAAAG













1318




CACUUUCA CUGAUGA X GAA AGAGAGCC




GGCUCUCUA UGAAAGUG













1334




GCGAGGGA CUGAUGA X GAA AUGCCUUC




GAAGGCAUU UCCCUCGC













1335




GGCGAGGG CUGAUGA X GAA AAUGCCUU




AAGGCAUUU CCCUCGCC













1336




CGGCGAGG CUGAUGA X GAA AAAUGCCU




AGGCAUUUC CCUCGCCG













1340




CUUCCGGC CUGAUGA X GAA AGGGAAAU




AUUUCCCUC GCCGGAAG













1350




AACCAUAC CUGAUGA X GAA ACUUGGGG




CCGGAAGUU GUAUGUUU













1353




UUUAACCA CUGAUGA X GAA ACAACUUC




GAAGUUUUA UGGUUAAA













1358




CAUCUUUU CUGAUGA X GAA ACCAUACA




UGUAUGGUU AAAAGAUG













1359




CCAUCUUU CUGAUGA X GAA AACCAUAC




GUAUGGUUA AAAGAUGG













1370




UCGCAGGU CUGAUGA X GAA ACCCAUCU




AGAUGGGUU ACCUGCGA













1371




GUCGCAGG CUGAUGA X GAA AACCCAUC




GAUGGGUUA CCUGCGAC













1388




AGCGAGCA CUGAUGA X GAA AUUUCUCA




UGAGAAAUC UGCUCGCU













1393




CAAAUAGC CUGAUGA X GAA AGCAGAUU




AAUCUGCUC GCUAUUUG













1397




GAGUCGAA CUGAUGA X GAA AGGGAGCA




UGCUCGCUA UUUGACUC













1399




ACGAGUCA CUGAUGA X GAA AUAGCGAG




CUGGCUAUU UGACUCGU













1400




CACGAGUC CUGAUGA X GAA AAUAGUGA




UCGCUAUUU GACUCGUG













1405




GUAGCCAC CUGAUGA X GAA AGUCAAAU




AUUUGACUC GUGGUUAC













1412




UUAACGAG CUGAUGA X GAA AGCCACGA




UCGUGGCUA CACGUUAA













1415




UAAUUAAC CUGAUGA X GAA AGUAGCGA




UGGCUACUC GUUAAUUA













1418




UGAUAAUU CUGAUGA X GAA ACGAGUAG




CUACUCGUU AAUUAUCA













1419




UUGAUAAU CUGAUGA X GAA AAGGAAUA




UACUCGUUA AUUAUCAA













1422




UCCUUGAU CUGAUGA X GAA AUUGACGA




UCGUCAAUU AUCAAGGA













1423




GUCCUUGA CUGAUGA X GAA AAUUAACG




CGUUAAUUA UCAAGGAC













1425




ACGUCCUU CUGAUGA X GAA AUAAUUAA




UUAAUUAUC AAGGAGGU













1434




UCUUCAGU CUGAUGA X GAA ACGUCCUU




AAGGACGUA ACUGAAGA













1456




GAUUGUAU CUGAUGA X GAA AUUCCCUG




CAGGGAAUU AUACAAUC













1457




AGAUUCCA CUGAUGA X GAA AAUUCCCU




AGGGAAUUA UACAAUCU













1459




CAAGAUUG CUGAUGA X GAA AUAAUUCC




GGAAUUAUA CAAUCUUG













1464




CUCAGCAA CUGAUGA X GAA AUUGUAUA




UAUACAAUC UUGCUGAG













1466




UGCUCAGC CUGAUGA X GAA AGAUUCUA




UACAAUCUU GCUGAGCA













1476




GACUGUUU CUGAUGA X GAA AUGCUCAG




CUCAGCAUA AAACAGUC













1484




ACACAUUU CUGAUGA X GAA ACUGUUUU




AAAACAGUC AAAUGUGU













1493




GGUUUUUA CUGAUGA X GAA ACACAUUU




AAAUGUGUU UAAAAACC













1494




AGGUUUUU CUGAUGA X GAA AACACAUU




AAUGUGUUU AAAAACCU













1495




GAGGUUUU CUGAUGA X GAA AAACACAU




AUGUGUUUA AAAACCUC













1503




GUGCAAAU CUGAUGA X GAA AGGUUUUU




AAAAACCUC ACUGCCAC













1513




GACAAUUA CUGAUGA X GAA AGUGGCAG




CUGCCACUC UAAUUGUC













1515




UUGACAAU CUGAUGA X GAA AGAGUGGC




GCCACUCUA AUUGUCAA













1518




ACAUUGAC CUGAUGA X GAA AUUAGAGU




ACUCUAAUU GUCAAUGU













1521




UUCAUUUU CUGAUGA X GAA ACAAUUAG




CUAAUUGUC AAUGUGAA













1539




UUUUCGUA CUGAUGA X GAA AUCUGGGG




CCCCAGAUU UACGAAAA













1540




CUUUUCGU CUGAUGA X GAA AAUGUGGG




CCCAGAUUU ACGAAAAG













1541




CCUUUUCG CUGAUGA X GAA AAAUCUGG




CCAGAUUUA CGAAAAGG













1556




GAAACGAU CUGAUGA X GAA ACACGGCC




GGCCGUGUC AUCGUUUC













1559




CUGGAAAC CUGAUGA X GAA AUGACACG




CGUGUCAUC GUUUCCAG













1562




GGUCUGGA CUGAUGA X GAA ACGAUGAC




GUCAUCGUU UCCAGACC













1563




GGGUCUGG CUGAUGA X GAA AGCGAGGA




UCAUCGUUU CCAGACCC













1564




CGGGUCCG CUGAUGA X GAA AAACGAUG




CAUCGUUUC CAGACCCG













1576




UGGGCAGA CUGAUGA X GAA AGCCGGGU




ACCCGGCUC UCCACCCA













1578




AGUGGGUA CUGAUGA X GAA AGAGCCGG




CCCCCUCUC UACCCACU













1580




CCAGUGGG CUGAUGA X GAA AGAGAGCC




GGCUCUCUA CCCACUGG













1602




CAAGUCAG CUGAUGA X GAA AUUUGUCU




AGACAAAUC CUGACUUG













1609




UGCGGUAC CUGAUGA X GAA AGUCAGGA




UCCUGACUU GUACCGCA













1612




AUAUGCGG CUGAUGA X GAA ACAAGUCA




UGACUUGUA CCGCAUAU













1619




GGAUACCA CUGAUGA X GAA AUGCGGUA




UACCGCAUA AGGUAUCC













1624




UUGAGGGA CUGAUGA X GAA ACCAUAUG




CAUAUGGUA UCCCUCAA













1626




GGUUGAGG CUGAUGA X GAA AUACCAUA




UAUGGUAUC CCUCAACC













1630




UGUAGGUU CUGAUGA X GAA AGGGAGAC




GUAUCCCUC AACCUCCA













1636




CUUGAUUG CUGAUGA X GAA AGGUUGAG




CUCAACCUA CAAUCAAG













1641




AACCACUU CUGAUGA X GAA AUUGUAGG




CCCACAAUC AAGUGGUU













1649




GGUGCCAG CUGAUGA X GAA ACCACUUG




CAAGUGGUU CUGGCACC













1650




GGGUGCCA CUGAUGA X GAA AACCACUU




AAGUGGUUC UGGCACCC













1663




AUUAUGGU CUGAUGA X GAA ACAGGGGU




ACCCCUGUA ACCAGAAU













1669




GGAAUGAU CUGAUGA X GAA AUGGUUAC




GUAACCAUA AUCAUUCC













1672




UUCGGAAU CUGAUGA X GAA AUUAUGGU




ACCAUAAUC AUUCCGAA













1675




UGCUUCGG CUGAUGA X GAA AUGAUUAU




AUAAUCAUU CCGAAGCA













1676




UUGCUUCG CUGAUGA X GAA AAUGAUUA




UAAUCAUUC CGAAGCAA













1694




UGGAACAA CUGAUGA X GAA AGUCACAC




GUGUGACUU UUGUUCCA













1695




UUGGAACA CUGAUGA X GAA AAGUCACA




UGUGACUUU UGUUCCAA













1696




AUUGGAAC CUGAUGA X GAA AAAGUCAC




GUGACUUUU GUUCCAAU













1699




AUUAUUGG CUGAUGA X GAA ACAAAAGU




ACUUUUGUU CCAAUAAU













1700




CAUUAUUG CUGAUGA X GAA AACAAAAG




CUUUUGUUC CAAUAAUG













1705




CUCUUCAU CUGAUGA X GAA AUUGGAAC




GUUCCAAUA AUGAAGAG













1715




GGAUAAAG CUGAUGA X GAA ACUCUUCA




UGAAGAGUC CUUUAUCC













1718




CCAGGAUA CUGAUGA X GAA AGGACUCU




AGAGUCCUU UAUCCUGG













1719




UCCAGGAU CUGAUGA X GAA AAGGACUC




GAGUCCUUU AUCCUGGA













1720




AUCCAGGA CUGAUGA X GAA AAAGGACU




AGUCCUUUA UCCUGGAU













1722




GCAUCCAG CUGAUGA X GAA AUAAAGGA




UCCUUUAUC CUGGAUGC













1755




AUGCUCUC CUGAUGA X GAA AUUCUGUU




AACAGAAUU GAGAGCAU













1764




CGCUGAGU CUGAUGA X GAA AUGCUCUC




GAGAGCAUC ACUCAGCG













1768




CAUGCGCU CUGAUGA X GAA AGUGAGGC




CCAUCACUC AGCGCAUG













1782




CCUUCUAU CUGAUGA X GAA AUUGCCAU




AUGGCAAUA AUAGAAGG













1785




UUUCCUUC CUGAUGA X GAA AUUAUUGC




GCAAUAAUA GAAGGAAA













1798




AGCCAUCU CUGAUGA X GAA AUUCUUUC




GAAAGAAUA AGAUGGCU













1807




CAAGGUGC CUGAUGA X GAA AGCCAUCU




AGAUGGCUA GCACCUUG













1814




CCACAACC CUGAUGA X GAA AGGUGCUA




UAGCACCUU GGUUGUGG













1818




UCAGCCAC CUGAUGA X GAA ACCAAGGU




ACCUUGGUU GUGGCUGA













1829




AAAUUCUA CUGAUGA X GAA AGUCAGCC




GGCUGACUC UAGAAUUU













1831




AGAAAUUC CUGAUGA X GAA AGAGUCAG




CUGACUCUA GAAUUUCU













1836




AUUCCAGA CUGAUGA X GAA AUUCUAGA




UCUAGAAUU UCUGGAAU













1837




GAUUCCAG CUGAUGA X GAA AAUUCUAG




CUAGAAUUU CUGGAAUC













1838




AGAUUCCA CUGAUGA X GAA AAAUUCCA




UAGAAUUUC UGGAAUCU













1845




CAAAUGUA CUGAUGA X GAA AUUCCAGA




UCUGGAAUC UACAUUUG













1847




UGCAAAUG CUGAUGA X GAA AGAUUCCA




UGGAAUCUA CAUUUGCA













1851




GCUAUGCA CUGAUGA X GAA AUGUAGAU




AUCUACAUU UGCAUAGC













1852




AGCUAUGC CUGAUGA X GAA AAUGUAGA




UCUACAUUU GCAUAGCU













1857




UUGGAAGC CUGAUGA X GAA AUGCAAAU




AUUUGCAUA GCUUCCAA













1861




UUUAUUGG CUGAUGA X GAA AGCGAUGC




GCAUAGCUU CCAAUAAA













1862




CUUUAUUG CUGAUGA X GAA AAGCUAUG




CAUAGCUUC CAAUAAAG













1867




CCCAACUU CUGAUGA X GAA AUUAGAAG




CUUCCAAUA AAGUUGGG













1872




ACAGUCCC CUGAUGA X GAA ACUUUAUU




AAUAAAGUU GGGACUGU













1893




UAAAAGCU CUGAUGA X GAA AUGUUUCU




AGAAACAUA AGCUUUUA













1898




UGAUAUAA CUGAUGA X GAA ACCUCAUG




CAUAAGCUU UUAUAUCA













1899




GUGAUAUA CUGAUGA X GAA AAGCUUAU




AUAAGCUUU UAUAUCAC













1900




UGUGAUAU CUGAUGA X GAA AAAGCUUA




UAAGCUUUU AUAUCACA













1901




CUGUGAUA CUGAUGA X GAA AAAAGCUU




AAGCUUUUA UAUCACAG













1903




AUCUGUGA CUGAUGA X GAA AUAAAAGC




GCUUUUACA UCACAGAU













1905




ACAUCUGU CUGAUGA X GAA AUAUAAAA




UUUUUUAUC ACAGAUGU













1925




UAACAUGA CUGAUGA X GAA ACCCAUUU




AAAUGGGUU UCAUGUUA













1926




UUAACAUG CUGAUGA X GAA AACCCAUU




AAUGGGUUU CAUGUUAA













1927




GUUAACAU CUGAUGA X GAA AAACCCAU




AUGGGUUUC AUGUUAAC













1932




UCCAAGUU CUGAUGA X GAA ACAUGAAA




UUUCAUAAU AACUUGGA













1933




UUCCCAGU CUGAUGA X GAA AACAUGAA




UUCAUGUUA ACUUGGAA













1937




UUUUUUCC CUGAUGA X GAA AGUUAACA




UGUUAACUU UGUUAACU













1976




CUGUGCAA CUGAUGA X GAA ACAGUUUC




GAAACUGUC UUGCACAG













1378




AACUGUGC CUGAUGA X GAA AGACAGUU




AACUGUCUU GCACAGUU













1986




AACUUGUU CUGAUGA X GAA ACUGUGCA




UGCACAGUU AACAAGUU













1987




GAACUAAU CUGAUGA X GAA AACUGUGC




GCACAGUUA ACAAGUUC













1994




UGUAUAAG CUGAUGA X GAA ACUUGUUA




UAACAAGUU CUUAUACA













1995




CUGUAUAA CUGAUGA X GAA AACUUGUU




AACAAGUUC UUAUACAG













1997




CUCUGUAU CUGAUGA X GAA AGAACUUG




CAAGUUCUU AUACAGAG













1998




UCUCUGUA CUGAUGA X GAA AAGAACUU




AAGUUCUUA UACAGAGA













2000




CGUCUCUG CUGAUGA X GAA AUAAAGAC




GUUCUUAUA CAGAGACG













2010




AUCCAAGU CUGAUGA X GAA ACCUCUCU




AGAGACGUU ACUUGGAU













2011




AAUCCAAG CUGAUGA X GAA AACGUCUC




GAGACGUUA CUUGGAUU













2014




UAAAAUCC CUGAUGA X GAA AGUAACGU




ACGUUACUU GGAUUUUA













2019




CGCAGUAA CUGAUGA X GAA AUCCAAGU




ACUUGGAUU UUACUGCG













2020




CCGCAGUA CUGAUGA X GAA AAUCCAAG




CUUGGAUUU UACUGCGG













2021




UCCGCAGU CUGAUGA X GAA AAAUCCCA




UUGGAUUUU ACUGCGGA













2022




GUCCACAG CUGAUGA X GAA AAAAUCCA




UGGAUUUUA CUGCGGAC













2034




CUGUUAUU CUGAUGA X GAA ACUGUCCG




CGGACAGUU AAUAACAG













2035




UCUGUUAU CUGAUGA X GAA AACUGUCC




GGACAGUUA AUAACAGA













2038




UGUUCUGU CUGAUGA X GAA AUUAACUG




CAGUUAAUA ACAGAACA













2054




UAAUACUG CUGAUGA X GAA AGUGCAUU




AAUGCACUA CAGUAUUA













2059




CUUGCUAA CUGAUGA X GAA ACUGUAGU




ACUACAGUA UUAGCAAG













2061




UGCUUGCU CUGAUGA X GAA AUACUGUA




UACAGUAUU AGCAAGCA













2062




UUGCUUGC CUGAUGA X GAA AAUACUGU




ACAGUAUUA GCAAGCAA













2082




UCCUUAGU CUGAUGA X GAA AUGGCCAU




AUGGCCAUC ACUAAGGA













2086




GUGCUCCU CUGAUGA X GAA AGUGAUGG




CCAUCACUA AGGAGCAC













2096




GAGUGCUG CUGAUGA X GAA AGUGCUCC




GGAGCACUC CAUCACUC













2100




UUAAGAGU CUGAUGA X GAA AUGGAGUG




CACUCCAUC ACUCUUAA













2104




AAGAUUAA CUGAUGA X GAA AGUGAUGG




CCAUCACUC UUAAUCUU













2106




GUAAGAUU CUGAUGA X GAA AGAGUGAU




AUCACUCUU AAUCUUAC













2107




GGUAAGAU CUGAUGA X GAA AAGAGUGA




UCACUCUUA AUCUUACC













2110




GAUGGGAA CUGAUGA X GAA AUUAAGAG




CUCUUAAUC UUACCAUC













2112




AUGAUGGU CUGAUGA X GAA AGAUUAAG




CUUAAUCUU ACCAUCAU













2113




CAUGAUGG CUGAUGA X GAA AAGAUUAA




UUAAUCUUA CCAUCAUG













2118




ACAUUCAU CUGAUGA X GAA AUGGUAAG




CUUACCAUC AUGAAUGU













2127




UGCAGGGA CUGAUGA X GAA ACAUUCAU




AUGAAUGUU UCCCUGCA













2128




UUGCAGGG CUGAUGA X GAA AACAUUCA




UGAAUGUUU CCCUGCAA













2129




CUUGCAGG CUGAUGA X GAA AAACAUUC




GAAUGUUUC CCUGCAAG













2140




GGUGCCUG CUGAUGA X GAA AUCUUGCA




UGCAAGAUU CAGGCACC













2141




AGGUGUCU CUGAUGA X GAA AAUCUUGC




GCAAGAUUC AGGCACCU













2150




UGCAGGCA CUGAUGA X GAA AGGUGCCU




AGGCACCUA UGCCUGCA













2172




CCUGUCCA CUGAUGA X GAA ACAUUCCU




AGGAAUGUA UACACAGG













2174




CCCCUGUG CUGAUGA X GAA AUACAUUC




GAAUUUAUA CACAGGOG













2190




UUCUGAGG CUGAUGA X GAA AUUCCUUC




GAAGAAAUC CUCCAGAA













2193




UUCUUCUG CUGAUGA X GAA AGGAUUUC




GAAAUCCUC CAGAAGAA













2208




CUGAUUGU CUGAUGA X GAA AUUUCUUU




AAAGAAAUU ACAAUCAG













2209




UCUGAUUG CUGAUGA X GAA AAUUUCUU




AAGAAAUUA CAAUCAGA













2214




UGAUCUCU CUGAUGA X GAA AUUGUAAU




AUUACAAUC AGAGAUCA













2221




UGCUUCCU CUGAUGA X GAA AUCUCUGA




UCAGAGAUC AGGAAGCA













2234




GCAGGAGG CUGAUGA X GAA AUGGUGCU




AGCACCAUA CCUCCUGC













2238




UUUCGCAG CUGAUGA X GAA AGGUAUGG




CCAUACCUC CUGCGAAA













2250




UGAUCACU CUGAUGA X GAA AGGUUUCG




CGAAACCUC AGUGAUCA













2257




CACUGUGU CUGAUGA X GAA AUCACUGA




UCAGUGAUC ACACAGUG













2271




GAACUGCU CUGAUGA X GAA AUGGCCAC




GUGGCCAUC AGCAAUUC













2278




AGUGGUGG CUGAUGA X GAA ACUGCUGA




UCAGCAGUU CCACCACU













2279




AAGUGGUG CUGAUGA X GAA AACAGCUG




CAGCAGUUC CACCACUU













2287




ACAGUCUA CUGAUGA X GAA AGUGGUGG




CCACCACUU UAGACUGU













2288




GACAGUCU CUGAUGA X GAA AAGUGGUG




CACCACUUU AGACUGUC













2289




UGACAGUC CUGAUGA X GAA AAAGUGGU




ACCACUUUA GACUGUCA













2296




AUUAGCAU CUGAUGA X GAA ACAGUCUA




UAGACUGUC AUGCUAAU













2302




GACACCAU CUGAUGA X GAA AGCAUGAC




GUCAUGCUA AUGGUGUC













2310




GGCUCGGG CUGAUGA X GAA ACACCAUU




AAUGGUGUC CCCGAGCC













2320




AGUGAUCU CUGAUGA X GAA AGCCUUGG




CCGAGCCUC AGAUCACU













2325




AACCAAGU CUGAUGA X GAA AUCUGAGG




CCUCAGAUC ACUUGGUU













2329




UUUAAAUC CUGAUGA X GAA AGUGAUCU




AGAUCACUU GGUUUAAA













2333




UGUUUUGA CUGAUGA X GAA ACCAAGUG




CACUUGGUU UAAAAACA













2334




UUGUUUUU CUGAUGA X GAA AACCAAGU




ACUUGGUUU AAAAACAA













2335




GUUGUUUU CUGAUGA X GAA AAACCAAG




CUUGGUUUA AAAAGAAC













2352




UCUUGUUG CUGAUGA X GAA AUUUUGUG




CACAAAAUA CAACAAGA













2370




CCUAAAAU CUGAUGA X GAA AUUCCAGG




CCUGGAAUU AUUUUAGG













2371




UCCUAAAA CUGAUGA X GAA AAUUCCAG




CUGGAAUUA UUUUAGGA













2373




GGUCCUAA CUGAUGA X GAA AUAAUUCC




GGAAUUAUU UUAGGACC













2374




UGGUCCUA CUGAUGA X GAA AAUAAUUC




GAAUUAUUU UAGGACCA













2375




CUGGUCCU CUGAUGA X GAA AAAUAAUU




AAUUAUUUU AGGACCAG













2376




CCUGGUCC CUGAUGA X GAA AAAAUAAU




AUUAUUUUA GGACCAGG













2399




UUUCAAUA CUGAUGA X GAA ACAGCGUG




CACGCUGUU UAUUGAAA













2400




CUUUCAAU CUGAUGA X GAA AACAGCGU




ACGCUGUUU AUUGAAAG













2401




UCUUUCAA CUGAUGA X GAA AAACAGCG




CGCUGUUUA UUGAAAGA













2403




ACUCUUUC CUGAUGA X GAA AUAAACAG




CUGUUUAUU GAAAGAGU













2412




UCUUCUGU CUGAUGA X GAA ACUCUUUC




GAAAGAGUC ACAGAAGA













2433




CAGUGAUA CUGAUGA X GAA ACACCUUC




GAAGGUGUC UAUCACUG













2435




UGCAGUGA CUGAUGA X GAA AGACACCU




AGGUGUCUA UCACUGCA













2437




UUUGCAGU CUGAUGA X GAA AUAGACAC




GUGUCUAUC ACUGCAAA













2465




UUUCCACA CUGAUGA X GAA AGCCCUUC




GAAGGGCUC UGUGGAAA













2476




GUAUGCUG CUGAUGA X GAA ACUUUCCA




UGGAAAGUU CAGCAUAC













2477




GGUAUGCU CUGAUGA X GAA AACUUUCC




GGAAAGUUC AGCAUACC













2483




CAGUGAGG CUGAUGA X GAA AUGCUGAA




UUCAGCAUA CCUCACUG













2487




UGAACAGU CUGAUGA X GAA AGGUAUGC




GCAUACCUC ACUGUUCA













2493




GUUCCUUG CUGAUGA X GAA ACAGUGAG




CUCACUGUU CAAGGAAC













2494




GGUUCCUU CUGAUGA X GAA AACAGUGA




UCACUGUUC AAGGAACC













2504




ACUUGUCC CUGAUGA X GAA AGGUUCCU




AGGAACCUC GGACAAGU













2513




CCAGAUUA CUGAUGA X GAA ACUUGUCC




CGACAAGUC UAAUCUOG













2515




CUCCAGAU CUGAUGA X GAA AGACUUGU




ACAAGUCUA AUCUGGAG













2518




CAGCUCCA CUGAUGA X GAA AUUAGACU




AGUCUAAUC UGGAGCUG













2529




GUUAGAGU CUGAUGA X GAA AUCAGCUC




GAGCUGAUC ACUCUAAC













2533




GCAUGUUA CUGAUGA X GAA AGUGAUCA




UGAUCACUC UAACAUGC













2535




GUGCAUGU CUGAUGA X GAA AGAGUGAU




AUCACUCUA ACAUGCAC













2560




CCAGAAGA CUGAUGA X GAA AGGUCGAG




CUCCGACUC UCUUCUCG













2562




AGCCAGAA CUGAUGA X GAA AGAGUUUC




GCGACUCUC UUCUGGCU













2564




GGAGCCAG CUGAUGA X GAA AGAGAGUC




GACUCUCUU CUGGCUCC













2565




AGGAGCCA CUGAUGA X GAA AAGAGAGU




ACUCUCUUC UGGCUCCU













2571




GUUAAUAG CUGAUGA X GAA AGCCAGAA




UUCUGGCUC CUAUUAAC













2574




AGGGUUAA CUGAUGA X GAA AGGAGCCA




UGGCUCCUA UUAACCCU













2576




GGAGGGUU CUGAUGA X GAA AUAGGAGC




GCUCCUAUU AACCCUCC













2577




AGGAGGGU CUGAUGA X GAA AAUAGGAG




CUCCUAUUA ACCUCUCU













2583




CGGAUAAG CUGAUGA X GAA AGGGUGAA




UUAACCCUC CUUAUCCG













2586




UUUCGGAU CUGAUGA X GAA AGGAGGGU




ACCCUCCUU AUCCGAAA













2587




UUUUCGGA CUGAUGA X GAA AAGGAGGG




CCCUCCUUA UCCGAAAA













2589




AUUUUUCG CUGAUGA X GAA AUAAGGAG




CUCCUUAUC CGAAAAAU













2606




CAAAAGAA CUGAUGA X GAA ACCUUUUC




GAAAAGGUC UUCUUCUG













2608




UUCAGAAG CUGAUGA X GAA AGACCUUU




AAAGGUCUU CUUCUGAA













2609




UUCCAGAA CUGAUGA X GAA AAGACCUU




AAGGUCUUC UUCUGAAA













2611




UAUUUCAG CUGAUGA X GAA AGAAGACC




GGUCUUCUU CUGAAAUA













2612




UUAUUUCA CUGAUGA X GAA AAGAAGAC




GUCUUCUUC UGAAAUAA













2619




UCAGUCUU CUGAUGA X GAA AUUUCAGA




UCUGAAAUA AAGACUGA













2630




UUGAUAGG CUGAUGA X GAA AGUCAGUC




GACUGAAUA CCUAUCAA













2634




AUAAUUGA CUGAUGA X GAA AGGUAGUC




GACUACCUA UCAAUUAU













2636




UUAUAAUU CUGAUGA X GAA AUAGGUAG




CUACCUAUC AAUUAUAA













2640




UCCAUUAU CUGAUGA X GAA AUUGAUAG




CUAUCAAUU AUAAUCGA













2641




GUCCAUUA CUGAUGA X GAA AAUUGAUA




UAUCAAUUA UAAUGGAC













2643




CGGUCCAU CUGAUGA X GAA AUAAUUGA




UCAAUUAUA AUGGACCC













2661




UCCAAAGG CUGAUGA X GAA ACUUCAUC




GAUGAAGUU CCUUUGGA













2662




AUCCAAAG CUGAUGA X GAA AACUUCAU




AUGAAGUUC CUUUGGAU













2665




CUCAUCCA CUGAUGA X GAA AGGAACUU




AAGUUCCUU UGGAUGAG













2666




GCUCAUCC CUGAUGA X GAA AAGGAACU




AGUUCCUUU GGAUGAGC













2688




UCAUAAGG CUGAUGA X GAA AGCCGCUC




GAGCGGCUC CCUUAUGA













2692




GGCAUCAU CUGAUGA X GAA AGGGAGCC




GGCUCCCUU AUGAUCCC













2693




UGGCAUCA CUGAUGA X GAA AAGGGAGC




GCUCCCUUA UGAUGCCA













2714




CCCGGGCA CUGAUGA X GAA ACUCCCAC




GUGGGAGUU UGCCCGGG













2715




UCCCGGGC CUGAUGA X GAA AACUCCCA




UGGGAGUUU GCCCGGGA













2730




CCCAGUUU CUGAUGA X GAA AGUCUCUC




GAGAGACUU AAACUGGG













2731




GCCCAGUU CUGAUGA X GAA AAGUCUCU




AGAGACUUA AACUGGGC













2744




UUCCAAGU CUGAUGA X GAA AUUUGCCC




GCCCAAAUC ACUUGGAA













2748




CCUCUUCC CUGAUGA X GAA AGUGAUUU




AAAUCACUU GGAAGAGG













2761




UUUUCCAA CUGAUGA X GAA AGCCCCUC




GAGGGGGUU UUGGAAAA













2762




CUUUUCCA CUGAUGA X GAA AAGCCCCU




AGGGGCUUU UGGAAAAG













2763




ACUUUUCC CUGAUGA X GAA AAAGCCCC




GGGGCUUUU GGAAAAGU













2775




GAUGCUUG CUGAUGA X GAA ACCACUUU




AAAGUGGUU CAAGCACC













2776




UGAUGCUU CUGAUGA X GAA AACCACUU




AAGUGGUUC AAGCAUCA













2783




CAAAUGCU CUGAUGA X GAA AUGCUUGA




UCAAGCAUC AGCAUUUG













2789




UAAUGCCA CUGAUGA X GAA AUGCUGAU




AUCAGCAUU UGGCAUUA













2790




UUAAUGCC CUGAUGA X GAA AAUGCUGA




UCAGCAUUU GCCAUUAA













2796




GAUUUCUU CUGAUGA X GAA AUGCCAAA




UUUGGCAUU AAGAAAUC













2797




UGAUUUCU CUGAUGA X GAA AAUGCCAA




UUGGCAUUA AGAAAUCA













2804




ACGUAGGU CUGAUGA X GAA AUUUCUUA




UAAGAAAUC ACCUACGU













2809




CCGGCACG CUGAUGA X GAA AGGUGAUU




AAUCACCUA CGUGCCGG













2864




GAGCUUUG CUGAUGA X GAA ACUCCCUG




CAGCGAGUA CAAAGCUC













2872




AGUCAUCA CUGAUGA X GAA AGCUUUGU




ACAAAGCUC UGAUGACU













2886




AAGAUUUU CUGAUGA X GAA AGCUCAGU




ACUGAGCCA AAAAUCUU













2892




UGGGUCAA CUGAUGA X GAA AUUUUUAG




CUAAAAAUC UUGACOCA













2894




UGUGGGUC CUGAUGA X GAA AGAUUUUU




AAAAAUCUU GACCCACA













2904




UGGUGGCC CUGAUGA X GAA AUGUGGGU




ACCCACAUU GGCCACCA













2914




CACGUUCA CUGAUGA X GAA AUGGUGGC




GCCACCAUC UGAACGUG













2925




AGCAGGUU CUGAUGA X GAA ACCACGUU




AACGUGGUU AACCUGCU













2926




CAGCAGGU CUGAUGA X GAA AACCACGU




ACGUGGUUA ACCUGCUG













2962




CACCAUCA CUGAUGA X GAA AGGCCCUC




GAGGGCCUC UGAUGGUG













2973




UAUUCAAC CUGAUGA X GAA AUCACCAU




AUGGUGAUU GUUGAAUA













2976




CAGUAUUC CUGAUGA X GAA ACAAUCAC




GUGAUUGUU GAAUACUG













2981




AUUUGCAG CUGAUGA X GAA AUUCAACA




UGUUGAAUA CUGCAAAU













2990




GAUUUCCA CUGAUGA X GAA AUUUGCAG




CUGCAAAUA UGGAAAUC













2998




GUUGGAGA CUGAUGA X GAA AUUUCCAU




AUGGAAAUC UCUCCAAC













3000




UAGUUGGA CUGAUGA X GAA AGAUUUCC




GGAAAUCUC UCCAACUA













3002




GGUAGUUG CUGAUGA X GAA AGAGAUUU




AAAUCUCUC CAACUACC













3008




UCUUGAGG CUGAUGA X GAA AGUUGGAG




CUCCAACUA CCUCAAGA













3012




UUGCUCUU CUGAUGA X GAA AGGUAGUU




AACUACCUC AAGAGCAA













3029




GAAAAAAU CUGAUGA X GAA AGUCACGU




ACGUGACUU AUUUUUUC













3030




AGAAAAAA CUGAUGA X GAA AAGUCACG




CGUGACUUA UUUUUUCU













3032




UGAGAAAA CUGAUGA X GAA AUAAGUCA




UGACUUAUU UUUUCUCA













3033




UUGAGAAA CUGAUGA X GAA AAUAAGUC




GACUUAUUU UUUCUCAA













3034




GUUGAGAA CUGAUGA X GAA AAAUAAGU




ACUUAUUUU UUCUCAAC













3035




UGUUGAGA CUGAUGA X GAA AAAAUAAG




CUUAUUUUU UCUCAACA













3036




UUGUUGAG CUGAUGA X GAA AAAAAUAA




UUAUUUUUU CUCAACAA













3037




CUUGUUGA CUGAUGA X GAA AAAAAAUA




UAUUUUUUC UCAACAAG













3039




UCCUUGUU CUGAUGA X GAA AGAAAAAA




UUUUUUCUC AACAAGGA













3057




UCCAUGUG CUGAUGA X GAA AGUGCUGC




GCAGCACUA CACAUGGA













3070




UUCUUUCU CUGAUGA X GAA AGGCUCCA




UGGAGCCUA AGAAAGAA













3120




ACGCUAUC CUGAUGA X GAA AGUCUUGG




CCAAGACUA GAUAGCGU













3124




GGUGACGC CUGAUGA X GAA AGCUAGUC




GACUAGAUA GCGUCACC













3129




CUGCUGGU CUGAUGA X GAA ACGCUAUC




GAUAGCGUC ACCAGCAG













3146




AGCUCGCA CUGAUGA X GAA AGCUUUCG




CGAAAGCUU UGCGAGCU













3147




GAGCUCGC CUGAUGA X GAA AAGCUUUC




GAAAGCUUU GCGAGCUC













3155




GAAAGCCG CUGAUGA X GAA AGCUCGCA




UGCGAGCUC CGGCUUUC













3161




CUUCCUGA CUGAUGA X GAA AGCCGGAG




CUCCGGCUU UCAGGAAG













3162




UCUUCCUG CUGAUGA X GAA AAGCCGGA




UCCGGCUUU CAGGAAGA













3163




AUCUUCCU CUGAUGA X GAA AAAGCCGG




CCGGCUUUC AGGAAGAU













3172




CAGACUUU CUGAUGA X GAA AUCUUCCU




AGGAAGAUA AAAGUCUG













3178




AUCACUCA CUGAUGA X GAA ACUUUUAU




AUAAAAGUC UGAGUGAU













3189




UCUUCCUC CUGAUGA X GAA ACAUCACU




AGUGAUGUU GAGGAAGA













3205




ACCGUCAG CUGAUGA X GAA AUCCUCCU




AGGAUGAUU CUUGACGU













3206




AACCGUCA CUGAUGA X GAA AAUCCUCC




GGAGGAUUC UGACGGUU













3214




CUUGUAGA CUGAUGA X GAA ACCGUCAG




CUGACGGUU UCUACAAG













3215




CCUUGCAG CUGAUGA X GAA AACCGUCA




UGACGGUUU CUACAAGG













3216




UCCUUGUA CUGAUGA X GAA AAACCGUC




GACGGUUUC UACAAGGA













3218




GCUCCUUG CUGAUGA X GAA AGAAACCG




CGGUUUCUA CAAGGAGC













3231




UCCAAAGU CUGAUGA X GAA AUGGGCUC




GAGCCCAUC ACUAUGGA













3235




AUCUUCCA CUGAUGA X GAA AGUGAUGG




CCAUCACUA UGGAAGAU













3244




AGAAAUCA CUGAUGA X GAA AUCUUCCA




UGGAAGAUC UGAUUUCU













3249




CUGUAAGA CUGAUGA X GAA AUCAGAUC




GAUCUGAUU UCUUACAG













3250




ACUGUAAG CUGAUGA X GAA AAUCAGAU




AUCUGAUUU CUUACAGU













3251




AACUGUAA CUGAUGA X GAA AAAUCAGA




UCUGAUUUC UUACAGUU













3253




AAAACUGU CUGAUGA X GAA AGAAAUCA




UGAUUUCUU ACAGUUUU













3254




GAAAACUG CUGAUGA X GAA AAGAAAUC




GAUUUCUUA CAGUUUUC













3259




CACUUGAA CUGAUGA X GAA ACUGUAAG




CUUACAGUU UUCAAGUG













3260




CCACUUGA CUGAUGA X GAA AACUGUAA




UUACAGUUU UCAAGUGG













3261




GCCACUUG CUGAUGA X GAA AAACUGUA




UACAGUUUU CAAGUGGC













3262




GGCCACUU CUGAUGA X GAA AAAACUGU




ACAGUUUUC AAGUGGCC













3284




AAGACAGG CUGAUGA X GAA ACUCCAUG




CAUGGAGUU CCUGUCUU













3285




GAAGACAG CUGAUGA X GAA AACUCCAU




AUGGAGUUC CUGUCUUC













3290




UUCUGGAA CUGAUGA X GAA ACAGGAAC




GUUCCUGUC UUCCAGAA













3292




CUUUCUGG CUGAUGA X GAA AGACAGGA




UCCUGUCUU CCAGAAAG













3293




ACUUUCUG CUGAUGA X GAA AAGACAGG




CCUGUCUUC CAGAAAGU













3306




UCCCGAUG CUGAUGA X GAA AUGCACUU




AAGUGCAUU CAUCGGGA













3307




GUCCCGAU CUGAUGA X GAA AAUGCACU




AGUGCAUUC AUCGGGAC













3310




CAGGUCCC CUGAUGA X GAA AUGAAUGC




GCAUUCAUC GGGACCUG













3333




GAUAAAAG CUGAUGA X GAA AUGUUUCU




AGAAACAUU CUUUUAUC













3334




AGAUAAAA CUGAUGA X GAA AAUGUUUC




GAAACAUUC UUUUAUCU













3336




UCAGAUAA CUGAUGA X GAA AGAAUGUU




AACAUUCUU UUAUCUGA













3337




CUCAGAUA CUGAUGA X GAA AAGAAUGU




ACAUUCUUU UAUCUGAG













3338




UCUCAGAU CUGAUGA X GAA AAAGAAUG




CAUUCUUUU AUCUGAGA













3339




UUCUCAGA CUGAUGA X GAA AAAAGAAU




AUUCUUUUA UCUGAGAA













3341




UGUUCUCA CUGAUGA X GAA AUAAAAGA




UCUUUUAUC UGAGAACA













3363




AAAUCACA CUGAUGA X GAA AUCUUCAC




GUGAAGAUU UGUGAUUU













3364




AAAAUCAC CUGAUGA X GAA AAUCUUCA




UGAAGAUUU GUGAUUUU













3370




AAGGCCAA CUGAUGA X GAA AUCACAAA




UUUGUGAUU UUGGCCUU













3371




CAAGGCCA CUGAUGA X GAA AAUCACAA




UUGUGAUUU UGGCCUUG













3372




GCAAGGCC CUGAUGA X GAA AAAUCACA




UGUGAUUUU GGCCUUGC













3378




UCUCUGGC CUGAUGA X GAA AGGCCAAA




UUUGGCCUU GCCCGGGA













3388




CUUAUAAA CUGAUGA X GAA AUCCCGGG




CCCGGGAUA UUUAUAAG













3390




UUCUUAUA CUGAUGA X GAA AUAUCCCG




CGGGAUAUU UAUAAGAA













3391




GUUCUUAU CUGAUGA X GAA AAUAUCCC




GGGAUAUUU AUAAGAAC













3392




GGUUCUGA CUGAUGA X GAA AAAUAUCC




GGAUAUUUA UAAGAACC













3394




GGGGUUCU CUGAUGA X GAA AUAAAUAU




AUAUUUAUA AGAACCCC













3406




UCUCACAU CUGAUGA X GAA AUCGGGGU




ACCCCGAUU AUGUGAGA













3407




UUCUCACA CUGAUGA X GAA AAUCGGGG




CCCCGAUUA UGUGAGAA













3424




AAGUCGAG CUGAUGA X GAA AUCUCCUU




AAGGAGAUA CUCGACUU













3427




AGGAAGUC CUGAUGA X GAA AGUAUCUC




GAGAUACUC GACUUCCU













3432




UUCAGAGG CUGAUGA X GAA AGUCGAGU




ACUCGACUU CCUCUGAA













3433




UUUCAGAG CUGAUGA X GAA AAGUCGAG




CUCGACUUC CUCUGAAA













3436




CCAUUUCA CUGAUGA X GAA AGGAAGUC




GACUUCCUC UGAAAUGG













3451




AGAUUCGG CUGAUGA X GAA AGCCAUUC




GGAUGGCUC CCGAAUCU













3458




CAAAGAUA CUGAUGA X GAA AUUCGGGA




UCCCGAAUC UAUCUUUG













3460




GUCAAAGA CUGAUGA X GAA AGAUUCUG




CCGAAUCUA UCUUUGAC













3462




UUGUCAAA CUGAUGA X GAA AUAGAUUC




GAAUCUAUC UUUGACAA













3464




UUUUGUCA CUGAUGA X GAA AGAUAGAU




AUCUAUCUU UGACAAAA













3465




AUUUUGUC CUGAUGA X GAA AAGAUAGA




UCUAUCUUU GACAAAAU













3474




GUGCUGUA CUGAUGA X GAA AUUUUGUC




GACAAAAUC UACAGCAC













3476




UGGUGCUG CUGAUGA X GAA AGAUUUUG




CAAAAUCUA CAGCACCA













3500




CUCCGUAA CUGAUGA X GAA ACCACACG




CGUGUGGUC UUACGGAG













3502




UACUCCGU CUGAUGA X GAA AGACCACA




UGUGGUCUU ACGGAGUA













3503




AUACUCCG CUGAUGA X GAA AAGACCAC




GUGGUCUUA CGGAGUAU













3510




CACAGCAA CUGAUGA X GAA ACUCCGUA




UACGGAGUA UUGCUGUG













3512




CCCACAGC CUGAUGA X GAA AUACUCCG




CGGAGUAUU GCUGUGGG













3525




AAGGAGAA CUGAUGA X GAA AUUUCCCA




UGGGAAAUC UUCUCCUU













3527




CUAAGGAG CUGAUGA X GAA AGAUUUCC




GGAAAUCUU CUCCUUAG













3528




CCUAAGGA CUGAUGA X GAA AAGAUUUC




GAAAUCUUC UCCUUAGG













3530




CAACUAAG CUGAUGA X GAA AGAAGAUU




AAUCUUCUC CUUAGGUG













3533




ACCCACCU CUGAUGA X GAA AGGAGAAG




CUUCUCCUU AGGUGGGU













3534




GACCCACC CUGAUGA X GAA AAGGAGAA




UUCUCCUUA GGUGGGUC













3542




GGUAUGGA CUGAUGA X GAA ACCCACCU




AGGUGGGUC UCCAUACC













3544




UGGGUAUG CUGAUGA X GAA AGACCCAC




GUGGGUCUC CAUACCCA













3548




CUCCUGGG CUGAUGA X GAA AUGGAGAC




GUCUCCAUA CCCAGGAG













3558




UCCAUUUG CUGAUGA X GAA ACUCCUGG




CCAGGAGUA CAAAUGGA













3575




GACUGCAA CUGAUGA X GAA AGUCCUCA




UGAGGACUU UUGCAGUC













3576




CGACUGCA CUGAUGA X GAA AAGUCCUC




GAGGACUUU UGCAGUCG













3577




GCGACUGC CUGAUGA X GAA AAAGUCCU




AGGACUUUU GCAGUCGC













3583




CCUCAGGC CUGAUGA X GAA ACUGCAAA




UUUGCAGUC GCCUGAGG













3613




GUACUCAG CUGAUGA X GAA AGCUCUCA




UGAGAGCUC CUGAGUAC













3620




GAGUAGAG CUGAUGA X GAA ACUCAGGA




UCCUGAGUA CUCUACUC













3623




CAGGAGUA CUGAUGA X GAA AGUCUCUC




UGAGUACUC UACUCCUG













3625




UUCAGGAG CUGAUGA X GAA AGAGUACU




AGUACUCUA CUCCUGAA













3628




GAUUUCAG CUGAUGA X GAA AGUAGAGU




ACUCUACUC CUGAAAUC













3636




AUCUGAUA CUGAUGA X GAA AUUUCAGG




CCUGAAAUC UAUCAGAU













3638




UGAUCUGA CUGAUGA X GAA AGAUUUCA




UGAAAUCUA UCAGAUCA













3640




CAUGAUCU CUGAUGA X GAA AUAGAUUU




AAAUCUAUC AGAUCAUG













3645




UCCAGCAU CUGAUGA X GAA AUCUGAUA




UAUCAGAUC AUGCUGGA













3689




GUUCUGCA CUGAUGA X GAA AUCUUGGC




GCCAAGAUU UGCAGAAC













3690




AGUUCUGC CUGAUGA X GAA AAUCUUGG




CCAAGAUUU GCAGAACU













3699




UUUUCCAC CUGAUGA X GAA AGUUCUGC




GCAGAACUU GUGGAAAA













3711




AAAUCACC CUGAUGA X GAA AGUUUUUC




GAAAAACUA GGUGAUUU













3718




UUGAAGCA CUGAUGA X GAA AUCACCUA




UAGGUGAUU UGCUUCAA













3719




CUUGAAGC CUGAUGA X GAA AAUCAGCU




AGGUGAUUU GCUUCAAG













3723




UUUGCUUG CUGAUGA X GAA AGCAAAUC




GAUUUGCUU CAAGCAAA













3724




AUUUGCUU CUGAUGA X GAA AAGCAAAU




AUUUGCUUC AAGCAAAU













3735




UCCUGUUG CUGAUGA X GAA ACAUUUGC




GCAAAUGUA CAACAGGA













3748




GUAGUCUU CUGAUGA X GAA ACCAUCCU




AGGAUGGUA AAGACUAC













3755




UUGGGAUG CUGAUGA X GAA AGUCUUUA




UAAAGACUA CAUCCCAA













3759




UUGAUUGG CUGAUGA X GAA AUGUAGUC




GACUACAUC CCAAUCAA













3765




AUGCCAUU CUGAUGA X GAA AUUGGGAU




AUCCCAAUC AAUGCCAU













3774




CCUGUCAG CUGAUGA X GAA AUGGCAUU




AAUGCCAUA CUGACAGG













3787




AAACCCAC CUGAUGA X GAA AUUUCCUG




CAGGAAAUA GUGGGUUU













3794




AGUAUGUA CUGAUGA X GAA ACCCACUA




UAGUGGGUU UACAUACU













3795




GAGUAUGU CUGAUGA X GAA AACCCACU




AGUGGGUUU ACAUACUC













3796




UCAGUAUG CUGAUGA X GAA AAACCCAC




GUGGGUUUA CAUACUCA













3800




GAGUUGAG CUGAUGA X GAA AUGUAAAC




GUUUACAUA CUCAACUC













3803




CAGGAGUU CUGAUGA X GAA AGUAUGUA




UACAUACUC ACCUCCUG













3808




GAAGGCAG CUGAUGA X GAA AGUUGAGU




ACUCAACUC CUGCCUUC













3815




CCUCAGAG CUGAUGA X GAA AGGCAGGA




UCCUGCCUU CUCUGAGG













3816




UCCUCAGA CUGAUGA X GAA AAGGCAGG




CCUGCCUUC UCUGAGGA













3818




AGUCCUCA CAGAUGA X GAA AGAAGGCA




UCCCUUCUC UGAGGACU













3827




CCUUGAAG CUGAUGA X GAA AGUCCUCA




AGAGGACUU CUUCAAGG













3828




UCCUUGAA CUGAUGA X GAA AAGUCCUC




GAGGACUUC UUCAAGGA













3830




UUUCCUUG CUGAUGA X GAA AGAAGUCC




GGACUUCUU CAAGGAAA













3831




CUUUCCUU CUGAUGA X GAA AAGAAGUC




GACUUCUUC AAGGAAAG













3841




AGCUGAAA CUGAUGA X GAA ACUUUCCU




AGGAAAGUA UUUCAGCU













3843




GGAGCUGA CUGAUGA X GAA AUACUUUC




GAAAGUAUU UCAGCUCC













3844




CGGAGCUG CUGAUGA X GAA AAUACUUU




AAAGUAUUU CAGCUCCG













3845




UCGGAGCU CUGAUGA X GAA AAAUACUU




AAGUAUUUC AGCUCCGA













3850




AAACUUCG CUGAUGA X GAA AGCUGAAA




UUUCAGCUC CGAAGUUU













3857




CUGAAUUA CUGAUGA X GAA ACUUCGGA




UCCGAAGUU UAAUUCAG













3858




CCUGAAUU CUGAUGA X GAA AACUUCGG




CCGAAGUUU AAUUCAGG













3859




UCCUGAAU CUGAUGA X GAA AAACUUCG




CGAAGUUUA AUUCAGGA













3862




GCUUCCUG CUGAUGA X GAA AUUAAACU




AGUUUAAUU CAGGAAGC













3863




AGCUUCCU CUGAUGA X GAA AAUUAAAC




GUUUAAUUC AGGAAGCU













3872




CAUCAUCA CUGAUGA X GAA AGCUUCCU




AGGAAGCUC UGAUGAUG













3882




ACAUAUCU CUGAUGA X GAA ACAUCAUC




GAUGAUGUC AGAUAUGU













3887




CAUUUACA CUGAUGA X GAA AUCUGACA




UGUCAGAUA UGUAAAUG













3891




AAAGCAUU CUGAUGA X GAA ACAUAUCU




AGAUAUGUA AAUGCUUU













3898




GAACUUGA CUGAUGA X GAA AGCAUUUA




UAAAUGCUU UCAAGUUC













3899




UGAACUUG CUGAUGA X GAA AAGCAUUU




AAAUGCUUU CAAGUUCA













3900




AUGAACUU CUGAUGA X GAA AAAGCAUU




AAUGCUUUC AAGUUCAU













3905




GGCUCAUG CUGAUGA X GAA ACUUGAAA




UUUCAAGUU CAUGAGCC













3906




AGGCUCAU CUGAUGA X GAA AACUUGAA




UUCAAGUUC AUGAGCCU













3924




AAGGUUUU CUGAUGA X GAA AUUCUUUC




GAAAGAAUC AAAACCUU













3932




GUUCUUCA CUGAUGA X GAA AGGUUUUG




CAAAACCUU UGAAGAAC













3933




AGUUCUUC CUGAUGA X GAA AAGGUUUU




AAAACCUUU GAAGAACU













3942




UUCGGUAA CUGAUGA X GAA AGUUCUUC




GAAGAACUU UUACCGAA













3943




AUUCGGUA CUGAUGA X GAA AAGUUCUU




AAGAACUUU UACGGAAU













3944




CAUUCGGU CUGAUGA X GAA AAAGUUCU




AGAACUUUU ACUGAAUG













3945




GCAUUCGG CUGAUGA X GAA AAAAGUUC




GAACUUUUA CCGAAUGC













3959




CAAACAUG CUGAUGA X GAA AGGUGGCA




UGCCAGCUC CAUGUUUG













3965




AGUCAUCA CUGAUGA X GAA ACAUGGAG




CUCCAUGUU UGAUGACU













3966




UAGUCAUC CUGAUGA X GAA AACAUGGA




UCCAUGUUU GAUGACUA













3974




CGCCCUGG CUGAUGA X GAA AGUCAUCA




UGAUGACUA CCAGGGCG













3994




GGCCAACA CUGAUGA X GAA AGUGCUGC




GCAGCACUC UGUUGGCC













3998




GAGAGGGC CUGAUGA X GAA ACAGAGUG




CACUCUGUU GGCCUCUC













4004




GCAUGGGA CUGAUGA X GAA AGGCCAAC




GUUGGCCUC UCCCAUGC













4006




CAGCAUGG CUGAUGA X GAA AGAGGCCA




UGGCCUCUC CCAUGCUG













4022




UCCAGGUG CUGAUGA X GAA AGCGUUCC




GAAGCGCUU CACCUGGA













4023




GUCCAGGU CUGAUGA X GAA AAGCGCUU




AAGCGCUUC ACCUGGAC













4052




UCUUGAGC CUGAUGA X GAA AGGCCUUG




CAAGGCCUC GCUCAAGA













4056




UCAAUCUU CUGAUGA X GAA AGCGAGGC




GCCUCGCUC AAGAUUGA













4062




CUCAAGUC CUGAUGA X GAA AUCUUGAG




CUCAAGAUU GACUUGAG













4067




UUACUCUC CUGAUGA X GAA AGUCAAUC




GAUUGACUU GAGAGUAA













4074




UUACUGGU CUGAUGA X GAA ACUCUCAA




UUGAGAGUA ACCAGUAA













4081




CUUACUUU CUGAUGA X GAA ACUGGUUA




UAACCAGUA AAAGUAAG













4087




CGACUCCU CUGAUGA X GAA ACUUUUAC




GUAAAAGUA AGGAGUCG













4094




ACAGCCCC CUGAUGA X GAA ACUCCUUA




UAAGGAGUC GGGGCUGU













4103




UGACAUCA CUGAUGA X GAA ACAGCCCC




GGGGCUGUC UGAUGUCA













4110




GGCCUGCU CUGAUGA X GAA ACAGCAGA




UCUGAUGUC AGCAGCUC













4123




AUGGCAGA CUGAUGA X GAA ACUGGGCC




GGGCCAGUU UCUGCCAU













4124




AAUGGCAG CUGAUGA X GAA AACUGGGC




GCCCAGUUU CUGCCAUU













4125




GAAUGGCA CUGAUGA X GAA AAACUGGG




CCCAGUUUC UGCCAUUC













4132




ACAGCUGG CUGAUGA X GAA AUGGCAGA




UCUGCCAUU CCAGCUGU













4133




CACAGCUG CUGAUGA X GAA AAUGGCAG




CUGCCAUUC CGGCUGUG













4149




CCUUCGCU CUGAUGA X GAA ACGUGCCC




GGGCACGUC AGCGAAGG













4169




CGUAGGUG CUGAUGA X GAA ACCUGGGC




GCGCAGGUU CACCUACG













4170




UCGUAGGU CUGAUGA X GAA AACCUGGG




CGCAGGUUC ACCUACGA













4175




CGUGGUCG CUGAUGA X GAA AGGUGAAC




GUUCACCUA CGACCACG













4203




CAGCACGC CUGAUGA X GAA AUUUUCUU




AGGAAAAUC GCGUGCUG













4214




GGGGCGGG CUGAUGA X GAA AGCAGCAC




GUGCUGCCC CCCGCCCC













4229




CCGAGUUG CUGAUGA X GAA AGUCUGGG




CCCAGACUA CAACUCGG













4235




GGACCACC CUGAUGA X GAA AGUUGUAG




CUACAACUC GGUGGUCC













4242




GAGUACAG CUGAUGA X GAA ACCACCGA




UCGGUGGUC CUGUACUC













4247




GGGUGGAG CUGAUGA X GAA ACAGGACC




GGUUCUGUA CUCCACCC













4250




GUGGGGUG CUGAUGA X GAA AGUACAGG




CCUGUACUC CACCCCAC













4263




AAACUCUA CUGAUGA X GAA AUGGGUGG




CCACCCAUC UAGAGUUU













4265




UCAAACUC CUGAUGA X GAA AGAUGGGU




ACCCAUCUA GAGUUUGA













4270




UCGUGUCA CUGAUGA X GAA ACUCUAGA




UCUAGAGUU UGACACGA













4271




UUCGUGUC CUGAUGA X GAA AACUCUAG




CUAGAGUUU GACACGAA













4284




CUAGAAAU CUGAUGA X GAA AGGCUUCG




CGAAGCCUU AUUUCUAG













4285




UCUAGAAA CUGAUGA X GAA AAGGCUUC




GAAGCCUUA UUUCUAGA













4287




CUUCUAGA CUGAUGA X GAA AUAAGGCU




AGCCUUAUU UCUAGAAG













4288




GCUUCUAG CUGAUGA X GAA AAUAAGGC




GCCUUAUUU CUAGAAGC













4289




UGCUUCUA CUGAUGA X GAA AAAUAAGG




CCUUAUUUC UAGAAGCA













4291




UGUGCUUC CUGAUGA X GAA AGAAAUAA




UUAUUUCUA GAAGCACA













4305




GGUAUAAA CUGAUGA X GAA ACACAUGU




ACAUGUGUA UUUAUACC













4307




GGGGUCUA CUGAUGA X GAA AUACACAU




AUGUGUAUU UAUACCCC













4308




GGGGGUAU CUGAUGA X GAA AAUACACA




UGUGUAUUU AUACCCCC













4309




UGGGGGUA CUGAUGA X GAA AAAUACAC




GUGUAUUUA UACCCCCA













4311




CCUGGGGG CUGAUGA X GAA AUAAAUAC




GUAUUUAUA CCCCCAGG













4325




GCAAAAGC CUGAUGA X GAA AGUUUCCU




AGGAAACUA GCUUUUGC













4329




ACUGGCAA CUGAUGA X GAA AGCUAGUU




AACUAGCUU UUGCCAGU













4330




UACUGGCA CUGAUGA X GAA AAACUAGU




ACUAGCUUU UGCCAGUA













4331




AUACUGGC CUGAUGA X GAA AAAGCUAG




CUAGCUUUU GCCAGUAU













4338




AUGCAUAA CUGAUGA X GAA ACUGGCAA




UUGCCAGUA UUAUGCAU













4340




AUAUGCAU CUGAUGA X GAA AUACUGGC




GCCAGUAUU AUGCAUAU













4341




UAUAUGCA CUGAUGA X GAA AAUACUCG




CCAGUAUUA UGCAUAUA













4347




AACUUAUA CUGAUGA X GAA AUGCAUAA




UUAUGCAUA UAUAAGUU













4349




UAAACUUA CUGAUGA X GAA AUAUGCAU




AUGCAUAUA UAAGUUUA













4351




UGUAAACU CUGAUGA X GAA AUAUAUGC




GCAUAUAUA AGUUUACA













4355




AACGUGUA CUGAUGA X GAA ACUUAUAU




AUAUAAGUU UACACCUU













4356




AAAGGUGU CUGAUGA X GAA AACUUAUA




UAUAAGUUU ACACCUUU













4357




UAAAGGUG CUGAUGA X GAA AAACUUAU




AUAAGUUUA CACCUUUA













4363




GAAAGAUA CUGAUGA X GAA AGGUGUAA




UUACACCUU UAUCUUUC













4364




GGAAAGAU CUGAUGA X GAA AAGGUGUA




UACACCUUU AUCUUUCC













4365




UAGAAAGA CUGAUGA X GAA AAAGGUGU




ACACCUUUA UCUUUCCA













4367




CAUGGAAA CUGAUGA X GAA AUAAAGGU




ACCUUUAUC UUUCCAUG













4369




CCCAUGGA CUGAUGA X GAA AGAUAAAG




CUUUAUCUU UCCAUGGG













4370




UCCCAUGG CUGAUGA X GAA AAGAUAAA




UUUAUCUUU CCAUGCGA













4371




CUCCCAUG CUGAUGA X GAA AAAGAUAA




UUAUCUUUC CAUGGGAG













4389




AUCACAAA CUGAUGA X GAA AGCAGCUG




CAGCUGCUU UUUGUGAU













4390




AAUCACAA CUGAUGA X GAA AAGCAGCU




AGCUGCUUU UUGUGAUU













4391




AAAUCACA CUGAUGA X GAA AAAGCAGC




GCUGCUUUU UGUGAUUU













4392




AAAAUCAC CUGAUGA X GAA AAAAGCAG




CUGCUUUUU GUGAUUUU













4398




AUUAAAAA CUGAUGA X GAA AUCACAAA




UUUGUGAUU UUAAAAAU













4399




UAUUAAAA CUGAUGA X GAA AAUCACAA




UUGUGAUUU UUUUAAUA













4400




CUAUUAAA CUGAUGA X GAA AAAUCACA




UGUGAUUUU UUUAAUAG













4401




ACUAUUAA CUGAUGA X GAA AAAAUCAC




GUGAUUUUU UUAAUAGU













4402




CACUAUUA CUGAUGA X GAA AAAAACCA




UGAUUUUUU UAAUAGUG













4403




GCACUAUU CUGAUGA X GAA AAAAAAUC




GAUUUUUUU AAUAGUGC













4404




AGCACUAU CUGAUGA X GAA AAAAAAAU




AUUUUUUUA AUAGUGCU













4407




AAAAGCAC CUGAUGA X GAA AUUAAAAA




UUUUUAAUA GUGCUUUU













4413




AAAAAAAA CUGAUGA X GAA AGCACUAU




AUAGUGCUU UUUUUUUU













4414




AAAAAAAA CUGAUGA X GAA AAGCACAA




UAGUGCUUU UUUUUUUU













4415




CAAAAAAA CUGAUGA X GAA AAAGCACU




AGUGCUUUU UUUUUUUG













4416




UCAAAAAA CUGAUGA X GAA AAAAGCAC




GUGCUUUUU UUUUUUGA













4417




GUCAAAAA CUGAUGA X GAA AAAAAGCA




UGCUUUUUU UUUUUGAC













4418




AGUCAAAA CUGAUGA X GAA AAAAAAGC




GCUUUUUUU UUUUGACU













4419




UAGUCAAA CUGAUGA X GAA AAAAAAAG




CUUUUUUUU UUUGACUA













4420




UUAGUCAA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UUGACUAA













4421




GUUAGUCA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UGACUAAC













4422




UGUUAGUC CUGAUGA X GAA AAAAAAAA




UUUUUUUUU GACUAACA













4427




AUUCUUGU CUGAUGA X GAA ACUCAAAA




UUUUGACUA ACAAGAAU













4438




UCUGGAGU CUGAUGA X GAA ACAUUCUU




AAGAAUGUA ACUCCAGA













4442




UCUAUCUG CUGAUGA X GAA AGUUACAU




AUGUAACUC CAGAUAGA













4448




UAUUUCUC CUGAUGA X GAA AUCUGGAG




CUCCAGAUA GAGAAAUA













4456




CUUGUCAC CUGAUGA X GAA AUUUCUCU




AGAGAAAUA GUGACAAG













4476




UUUAGCAG CUGAUGA X GAA AGUGUUCU




AGAACACUA CUGCUAAA













4482




UGAGGAUU CUGAUGA X GAA AGCAGUAG




CUACUGCUA AAUCCUCA













4486




AACAUGAG CUGAUGA X GAA AUUUAGCA




UGCUAAAUC CUCAUGUU













4489




AGUAACAU CUGAUGA X GAA AGGAUUUA




UAAAUCCUC AUGUUACU













4494




CACUGAGU CUGAUGA X GAA ACAUGAGG




CCUCAUGUU ACUCAGUG













4495




ACACUGAG CUGAUGA X GAA AACAUGAG




CUCAUGUUA CUCAGUGU













4498




CUAACACU CUGAUGA X GAA AGUAACAU




AUGUUACUC AGUGUUAG













4504




AUUUCUCU CUGAUGA X GAA ACACUGAG




CUCAGUGUU AGAGAAAU













4505




GAUUUCUC CUGAUGA X GAA AACACUGA




UCAGUGUUA GAGAAAUC













4513




UUAGGAAG CUGAUGA X GAA AUUUCUCU




AGAGAAAUC CUUCCUAA













4516




GGUUUAGG CUGAUGA X GAA AGGAUUUC




GAAAUCCUU CCUAAACC













4517




GGGUUUGG CUGAUGA X GAA AAGGAUUU




AAAUCCUUC CUAAACCC













4520




AUUGGGUU CUGAUGA X GAA AGGAAGGA




UCCUUCCUA AACCCAAU













4533




GAGCAGGG CUGAUGA X GAA AGUCAUUG




CAAUGACUU CCCUGCUC













4534




GGAGCAGG CUGAUGA X GAA AAGUCAUU




AAUGACUUC CCUGCUCC













4541




GGGGGUUG CUGAUGA X GAA AGCAGGGA




UCCCUGCUC CAACCCCC













4557




CGUGCCCU CUGAUGA X GAA AGGUGCCG




CCCCACCUC AGGGCACG













4576




CUCAAUCA CUGAUGA X GAA ACUGGUCC




GGACCAGUU UGAUUGAG













4577




CCUCAAUC CUGAUGA X GAA AACUGGUC




GACCAGUUU GAUUGAGG













4581




AGCUCCUC CUGAUGA X GAA AUCAAACU




AGUUUGAUU GAGGAGCU













4598




CAUUGGGU CUGAUGA X GAA AUCAGUGC




GCACUGAUC ACCCAAUG













4610




GGGUACGU CUGAUGA X GAA AUGCAUUG




CAAUGCAUC ACGUACCC













4615




CAGUGGGG CUGAUGA X GAA ACGUGAUG




CAUCACGUA CCCCACUG













4664




CUGGGGCU CUGAUGA X GAA ACGGGCUU




AAGCCCGUU AGCCCCAG













4665




CCUGGGGC CUGAUGA X GAA AACGGGCU




AGCCCGUUA GCCCCAGG













4678




CAGCCAGU CUGAUGA X GAA AUCCCCUG




CAGGGGAUC ACUGGCUG













4700




ACUCCCGA CUGAUGA X GAA AUGUUGCU




AGCAACAUC UCGGGAGU













4702




GGACUCCC CUGAUGA X GAA AGAUGUUG




CAACAUCUC GGGAGUCC













4709




UGCUAGAG CUGAUGA X GAA ACUCCCGA




UCGGGAGUG CUCUAGCA













4712




GCCUCCCA CUGAUGA X GAA AGGACUCC




GGAGUCCUC UAGCAGGC













4714




AGGCCUGC CUGAUGA X GAA AGAGGACU




AGUCCUCUA GCAGGCCU













4723




ACAUGUCU CUGAUGA X GAA AGGCCUGC




GCAGGCCUA AGACAUGU













4802




GCGUCUCA CUGAUGA X GAA AUUCUUUC




GAAAGAAUU UGAGACGC













4803




UGCGUCUC CUGAUGA X GAA AAUUCUUU




AAAGAAUUU GAGACGCA













4840




GCAUUCCU CUGAUGA X GAA AGCCCCGU




ACGGGGCUC AGCAAUGC













4852




GCCACUGA CUGAUGA X GAA AUGGCAUU




AAUGCCAUU UCAGUGGC













4853




AGCCACUG CUGAUGA X GAA AAUGGCAU




AUGCCAUUU CAGUGGCU













4854




AAGCCACU CUGAUGA X GAA AAAUGGCA




UGCCAUUUC AGUGGCUU













4862




GAGCUGGG CUGAUGA X GAA AGCCACUG




CAGUGGCUU CCCAGCUC













4863




AGAGCUGG CUGAUGA X GAA AAGCCACU




AGUGGCUUC CCAGCUCU













4870




AAGGGUCA CUGAUGA X GAA AGCUGGGA




UCCCAGCUC UGACCCUU













4878




AAAUGUAG CUGAUGA X GAA AGGGUCAG




CUGACCCUU CUACAUUU













4879




CAAAUGUA CUGAUGA X GAA AAGGGUCA




UGACCCUUC UACAUUUG













4881




CUCAAAUG CUGAUGA X GAA AGAAGGGU




ACCCUUCUA CAUUUGAG













4885




GGCCCUCA CUGAUGA X GAA AUGUAGAA




UUCUACAUU UGAGGGCC













4886




GGGCCCUC CUGAUGA X GAA AAUGUAGA




UCUACAUUU GAGGGCCC













4929




AUCCAGAA CUGAUGA X GAA AUGUCCCC




GGGGACAUU UUCUGGAU













4930




AAUCCAGA CUGAUGA X GAA AAUGUCCC




GGGACAUUU UCUGGAUU













4931




GAAUCCAG CUGAUGA X GAA AAAUGUCC




GGACAUUUU CUGGAUUC













4932




AGAAUCCA CUGAUGA X GAA AAAAUGUC




GACAUUUUC UGGAUUCU













4938




CCUCCCAG CUGAUGA X GAA AUCCAGAA




UUCUGGAUU CUGGGAGG













4939




GCCUCCCA CUGAUGA X GAA AAUCCAGA




UCUGGAUUC UGGGAGGC













4963




AAAAAAGA CUGAUGA X GAA AUUUGUCC




GGACAAAUA UCUUUUUU













4965




CCAAAAAA CUGAUGA X GAA AUAUUUGU




ACAAAUAUC UUUUUUGG













4967




UUCCAAAA CUGAUGA X GAA AGAUAUUU




AAAUAUCUU UUUUGGAA













4968




GUUCCAAA CUGAUGA X GAA AAGAUAUU




AAUAUCUUU UUUGGAAC













4969




AGUUCCAA CUGAUGA X GAA AAAGAUAU




AUUUCUUUU UUGGAACU













4970




UAGUUCCA CUGAUGA X GAA AAAAGAUA




UAUCUUUUU UGGAACUA













4971




UUAGUUCC CUGAUGA X GAA AAAAAGAU




AUCUUUUUU GGAACGAA













4978




AUUUGCUU CUGAUGA X GAA AGUUCCAA




UUGGAACUA AAGCAAAU













4987




AGGUCUAA CUGAUGA X GAA AUUUUGUU




AAGCAAAUU UUAGACCU













4988




AAGGUCUA CUGAUGA X GAA AAUUUGCU




AGCAAAUUU UAGACCUU













4989




AAAGGUCU CUGAUGA X GAA AAAUUUGC




GCAAAUUUU AGACCUUU













4990




UAAAGGUC CUGAUGA X GAA AAAAUUUG




CAAAUUUUA GACCUUUA













4996




CAUAGGUA CUGAUGA X GAA AGGUCUAA




UUAGACCUU UACCUAUG













4997




CCAUAGGU CUGAUGA X GAA AAGGUCUA




UAGACCUUU ACCUAUGG













4998




UCCAUAGG CUGAUGA X GAA AAAGGUCU




AGACCUUUA CCUAUGGA













5002




CACUUCCA CUGAUGA X GAA AGGUAAAG




CUUUACCUA UGGAAGUG













5013




GGACAUAG CUGAUGA X GAA ACCACUUC




GAAGUGGUU CUAUGUCC













5014




UGGACAUA CUGAUGA X GAA AACCACUU




AAGUGGUUC UAUGUCCA













5016




AAUGGACA CUGAUGA X GAA AGAACCAC




GUGGUUCUA UGUCCAUU













5020




UGAGAAUG CUGAUGA X GAA ACAUAGAA




UUCUAUGUC CAUUCUCA













5024




GGAAUGAG CUGAUGA X GAA AUGGACAU




AUGUCCAUU CUCAUUCG













5025




ACGAAUGA CUGAUGA X GAA AAUGGACA




UGUCCAUUC UCAUUCGU













5027




CCACGAAU CUGAUGA X GAA AGAAUCGA




UCCAUUCUC AUUCGUGG













5030




AUGCCACG CUGAUGA X GAA AUGAGAAU




AUUCUCAUU CGUGGCAU













5031




CAUGCCAC CUGAUGA X GAA AAUGAGAA




UUCUCAUUC GUGGCAUG













5041




CAAAUCAA CUGAUGA X GAA ACAUGCCA




UGGCAUGUU UUGAUUUG













5042




ACAAAUCA CUGAUGA X GAA AACAUGCC




GGCAUGUUU UGAUUUCU













5043




UACAAAUC CUGAUGA X GAA AAACAUGC




GCAUGUUUU GAUUUGUA













5047




GUUCUACA CUGAUGA X GAA AUCAAAAC




GUUUUGAUU UGUAGCAC













5048




AGUGCUAC CUGAUGA X GAA AAUCAAAA




UUUUGAUUU GUAGCACU













5051




CUCAGUGC CUGAUGA X GAA ACAAAUCA




UGAUUUGUA GCACUGAG













5069




UCAGAGUU CUGAUGA X GAA AGUGCCAC




GUGGCACUC AACUCUGA













5074




UGGGCUCA CUGAUGA X GAA AGUUGAGU




ACUCAACUC UGAGCCCA













5084




GCCAAAAG CUGAUGA X GAA AUGGGCUC




GAGCCCAUA CUUUUGGC













5087




GGAGCCAA CUGAUGA X GAA AGUAUGGG




CCCAUACUU UUGGCUCC













5088




AGGAGCCA CUGAUGA X GAA AAGUAUGG




CCAUACUUU UGGCUCCU













5089




GAGGAGCC CUGAUGA X GAA AAAGUAUG




CAUACUUUU GGCUCCUC













5094




UACUAGAG CUGAUGA X GAA AGCCAAAA




UUUUGGCUC CUCUAGUA













5097




UCUUACUA CUGAUGA X GAA AGGAGCCA




UGGCUCCUC UAGUAAGA













5099




CAUCUUAC CUGAUGA X GAA AGAGGAGC




GCUCCUCUA GUAAGAUG













5102




GUGCAUCU CUGAUGA X GAA ACUAGAGG




CCUCUAGUA AGAUGCAC













5119




CUCUGGCU CUGAUGA X GAA AGUUUUCA




UGAAAACUU AGCCAGAG













5120




ACUCUGGC CUGAUGA X GAA AAGUUUUC




GAAAACUUA GCCAGAGU













5129




GACAACCU CUGAUGA X GAA ACUCUGGC




GCCAGAGUU AGGUUGUC













5130




AGACAACC CUGAUGA X GAA AACUCUGG




CCAGAGUUA GGUUGUCU













5134




CUGGAGAC CUGAUGA X GAA ACCUAACU




AGUUAGGUU GUCUCCAG













5137




GGCCUGGA CUGAUGA X GAA ACAACCUA




UAGGUUGUC UCCAGGCC













5139




AUGGCCUG CUGAUGA X GAA AGACAACC




GGUUGUCUC CAGGCCAU













5156




UUCAGUGU CUGAUGA X GAA AUGCCAUC




GAUGGCCUU ACACUGAA













5157




UUUCAGUG CUGAUGA X GAA AAGGCCAU




AUGGCUUUA CACUGAAA













5170




UAGAAUGU CUGAUGA X GAA ACAUUUUC




GAAAAUGUC ACAUUCUA













5175




CAAAAUAG CUGAUGA X GAA AUGUGACA




UGUCACAUU CUAUUUUG













5176




CCAAAAUA CUGAUGA X GAA AAUGUGAC




GCCACAUUC UAUUUUGG













5178




ACCCAAAA CUGAUGA X GAA AGAAUGUG




CACAUUCUA UUUUGGGU













5180




AUACCCAA CUGAUGA X GAA AUAGAAUG




CAUUCAUUU UUGGGUAU













5181




AAUACCCA CUGAUGA X GAA AAUAGAAU




AUUCUAUUU UGGGUAUU













5182




UAAUACCC CUGAUGA X GAA AAAUAGAA




UUCUAUUUU GGGUAUUA













5187




UAUAUUAA CUGAUGA X GAA ACCCAAAA




UUUUGGGUA UUAAUAUA













5189




UAUAUAUU CUGAUGA X GAA AUACCCAA




UUGGGUAUU AAUAUAUA













5190




CUAUAUAU CUGAUGA X GAA AAUACCCA




UGGGUAUUA AUAUAUAG













5193




GGACUAUA CUGAUGA X GAA AUUAAUAC




GUAUUAAUA UAUAGUCC













5195




CUGGACUA CUGAUGA X GAA AUAUUAAU




AUUAAUAUA UAGUCCAG













5197




GUCUGGAC CUGAUGA X GAA AUAUAUUA




UAAUAUAUA GUCCAGAC













5200




AGUGUCUG CUGAUGA X GAA ACUAUAUA




UAUAUAGUC CAGACACU













5209




AUUGAGUU CUGAUGA X GAA AGUGUCUG




CAGACACUU AACUCAAU













5210




AAUUGAGU CUGAUGA X GAA AAGAGUCU




AGACACUUA ACUCAAUU













5214




AAGAAAUU CUGAUGA X GAA AGUUAAGU




ACUUAACUC AAUUUCUU













5218




UACCAAGA CUGAUGA X GAA AUUAAGUU




AACUCAAUU UCUUGGUA













5219




AUACCAAG CUGAUGA X GAA AAUUGAGU




ACUCAAUUU CUUGGUAU













5220




AAUACCAA CUGAUGA X GAA AAAAUAAG




CUCAAUUUC UUGGUAUU













5222




AUAAUACC CUGAUGA X GAA AGAAAUUG




CAAUUUCUU GGUAUUAU













5226




CAGAAUAA CUGAUGA X GAA ACCAAGAA




UUCUUGGUA UUAUUCUG













5228




AACAGAAU CUGAUGA X GAA AUACCAAG




CUUGGUAUU AUUCUGUU













5229




AAACAGAA CUGAUGA X GAA AAUACCAA




UUGGUAUUA UUCUGUUU













5231




CAAAACAG CUGAUGA X GAA AUAAUACC




GGUAUUAUU CUGUUUUG













5232




GCAAAACA CUGAUGA X GAA AAUAAUAC




GUAUUAUUC UGUUUUGC













5236




CUGUGCAA CUGAUGA X GAA ACAGAAUA




UAUUCUGUU UUGCACAG













5237




ACUGUGCA CUGAUGA X GAA AACAGAAU




AUUCUGUUU UGCACAGU













5238




AACUGUGC CUGAUGA X GAA AAACAGAA




UUCUGUUUU UCACAGUU













5246




UCACAACU CUGAUGA X GAA ACUGUGCA




UGCACAGUU AGUUGUGA













5247




UUCACAAC CUGAUGA X GAA AACUGUGC




GCACGUUCA GUUGUGAA













5250




UCUUUCAC CUGAUGA X GAA ACUUACUG




CAGUUAGUU GUGAAAGA













5284




CUCCUCAG CUGAUGA X GAA ACUGCAUU




AAUGCAGUC CUGAGGAG













5296




AUGGAGAA CUGAUGA X GAA ACUCUCCU




AGGAGAGUU UUCUCCAU













5297




UAUGGAGA CUGAUGA X GAA AACUCUCC




GGAGAGUUU UCUCCUUA













5298




AUAUGGAG CUGAUGA X GAA AAACUCUC




GAGAGUUUU CUCCAUAU













5299




GAUAUGGA CUGAUGA X GAA AAAACUCU




AGAGUUUUC UCCAUAUC













5301




UUGAUAUG CUGAUGA X GAA AGAAAACU




AGUUUUCUC CAUAUCAA













5305




CGUUUUGA CUGAUGA X GAA AUGGAGAA




UUCUCCACA UCAAAACG













5307




CUCGUUUU CUGAUGA X GAA AUAUUGAG




CUCCAUAUC AAAACGAG













5336




ACCUUAUU CUGAUGA X GAA ACCUUUUU




AAAAAGGUC AAUAAGGU













5340




CUUGACCU CUGAUGA X GAA AUUGACCU




AGGUCAAUA AGGUCAAG













5345




CUUCCCUU CUGAUGA X GAA ACCUUAUU




AAUAAGGUC AAGGGAAG













5361




GGUAUAGA CUGAUGA X GAA ACGGGGUC




GACCCCGUC UCUAUACC













5363




UUGGUAUA CUGAUGA X GAA AGACGGGG




CCCCGUCUC UAUACCAA













5365




GGUUGGUA CUGAUGA X GAA AGAGACGG




CCGUCUCCA UACCAACC













5367




UUGGUUGG CUGAUGA X GAA AUAGAGAC




GUCUCUAUA CCAACCAA













5382




UGUUGGUG CUGAUGA X GAA AUUGGUUU




AAACCAAUU CACCAACA













5383




GUGUUGGU CUGAUGA X GAA AAUUGGUU




AACCAAUUC ACCAACAC













5395




UGGGUCCC CUGAUGA X GAA ACUGUGUU




AACACAGUU GGGACCCA













5417




ACGUGACU CUGAUGA X GAA ACUUCCUG




CAGGAAGUC AGUCACGU













5421




GGAAACGU CUGAUGA X GAA ACUGACUU




AAGUCAGUC ACGUUUCC













5426




GAAAAGGA CUGAUGA X GAA ACGUGACU




AGUCACGUU UCCUUUUC













5427




UGAAAAGG CUGAUGA X GAA AACGUGAC




GUCACGUUU CCUUUUCA













5428




AGGAAAAG CUGAUGA X GAA AAACGUGA




UCACGUUUC CUUUUCAU













5431




UAAAUGAA CUGAUGA X GAA AGGAAACG




CGUUUCCUU UUCAUUUA













5432




UUAAAUGA CUGAUGA X GAA AAGGAAAC




GUUUCCUUU UCAUUUAA













5433




AUUAAAUG CUGAUGA X GAA AAAGGAAA




UUUCCUUUU CAUUUAAU













5434




CAUUAAAU CUGAUGA X GAA AAAAGGAA




UUCCUUUUC AUUUAUUG













5437




CCCCAUUA CUGAUGA X GAA AUGAAAAG




CUUUUCAUU UAAUGGGG













5438




UCCCCAUU CUGAUGA X GAA AAUGAAAA




UUUUCAUUU AAUGGGGA













5439




AUCCCCAU CUGAUGA X GAA AAAUGAAA




UUUCAUUUA AUGGGGAU













5448




GAUAGUGG CUGAUGA X GAA AUCCCCAU




AUGGGGAUU CCACUAUC













5449




AGAUAGUG CUGAUGA X GAA AAUCCCCA




UGGGGAUUC CACUAUCU













5454




GUGUGAGA CUGAUGA X GAA AGUGGAAU




AUUCCACUA UCUCACAC













5456




UAGUGUGA CUGAUGA X GAA AUAGUGGA




UCCACUAUC UCACACUA













5458




AUUAGUGU CUGAUGA X GAA AGAUAGUG




CACUAUCUC ACACUAAU













5464




UUUCAGAU CUGAUGA X GAA AGUGUGAG




CUCACACUA AUCUGAAA













5467




UCCUUUCA CUGAUGA X GAA AUUAGUGU




ACACUAAUC UAAAAGGA













5489




CGCCAGCU CUGAUGA X GAA AUGCUCUU




AAGAGCAUU AGCUGGCG













5490




GCGCCAGC CUGAUGA X GAA AAUGCUCU




AGAGCAUUA GCUGGCGC













5501




GUCCUGAA CUGAUGA X GAA AUGCGCCA




UGGCGCAUA UUAACCAC













5503




AAGUGCUU CUGAUGA X GAA AUAUGCGC




GCGCAUAUU AAGCACUU













5504




AAAGUGCU CUGAUGA X GAA AAUAUGCG




CGCAUAUUA AGCACUUU













5511




GGAGCUGA CUGAUGA X GAA AGUGCUUA




UAAGCACUU UAAGCUCC













5512




AGGAGCUU CUGAUGA X GAA AAGUGCUU




AAGGACUUU AAGCUCCU













5513




AAGGAGCU CUGAUGA X GAA AAAGUGCU




AGCACUUUA AGCUCCUU













5518




UAGUCAAG CUGAUGA X GAA AGCUUAAA




UUUAAGCUC CUUGAGUA













5521




UUUUACUC CUGAUGA X GAA AGGAGCUU




AAGCUCCUU GAGUAAAA













5526




CACCUUUU CUGAUGA X GAA ACUCAAGG




CCUUGAGUA AAAAGGUG













5537




AAAUUACA CUGAUGA X GAA ACCAGCUU




AAGGUGGUA UGUAAUUU













5541




GCACAAAU CUGAUGA X GAA AGAAACCA




UGGUAUGUA AUUUAUGC













5544




CUUGCACA CUGAUGA X GAA AUUACAUA




UAUGUAAUU UAUGCAAG













5545




CCUUGCAU CUGAUGA X GAA AAUUACAU




AUGUAAUUU AUGCAAGG













5546




ACCUUGCA CUGAUGA X GAA AAAUUACA




UGUAAUUUA UGCAAGGU













5555




UGGAGAAA CUGAUGA X GAA ACCUUGCA




UGCAAGGUA UUUCUCCA













5557




ACUGGAGA CUGAUGA X GAA AUACCUUG




CAAGGUAUU UCUCCAGU













5558




AACUGGAG CUGAUGA X GAA AAUACCUU




AAGGAAUUU CUCCAGUU













5559




CAACUGGA CUGAUGA X GAA AAAUACCU




AGGUAUUUC UCCAGUUG













5561




CCCAACUG CUGAUGA X GAA AGAAAUAC




GUAUUUCUC CAGUUGGG













5566




UGAGUCCC CUGAUGA X GAA ACUGGAGA




UCUCCAGUU GGGACUCA













5573




AAUAUCCU CUGAUGA X GAA AGUCCCAA




UUGGGACUC AGGAUAUU













5579




UUAACUAA CUGAUGA X GAA AUCCUGAG




CUCAGGACA UUAGUUAA













5581




CAUUAACU CUGAUGA X GAA AUAUCCUG




CAGGAUAUU AGUUAAUG













5582




UCAUUAAC CUGAUGA X GAA AAUAUCCU




AGGAUAUUA GUUAAUGA













5585




GGCUCAUU CUGAUGA X GAA ACUAAUAU




AUAUUAGUU AAUGAGCC













5586




UGGCUCAU CUGAUGA X GAA AACUAAUA




UAUUAGUUA AUGAGCCA













5596




CUUCUAGU CUGAUGA X GAA AUGGCUCA




UGAGCCAUC ACCAGAAG













5600




UUUUCUUC CUGAUGA X GAA AGUGAUGG




CCAUCACUA GAAGAAAA













5615




CAGUUGAA CUGAUGA X GAA AUGGGCUU




AAGCCCAUU UUCAACUG













5616




GCAGUUGA CUGAUGA X GAA AAUGGGCU




AGCCCAUUU UCAACUGC













5617




AGCAGUUG CUGAUGA X GAA AAAUGGGC




GCCCAUUUU CAACUCCU













5618




AAGCAGUU CUGAUGA X GAA AAAAUCGG




CCCAUUUUC AACUGCUU













5626




AAGUUUCA CUGAUGA X GAA AGCACUUG




CAACUGCUU UGAAACUU













5627




CAAGUUUC CUGAUGA X GAA AAGCAGUU




AACUGCUUU GAAACUUG













5634




CCCCAGGC CUGAUGA X GAA AGUUUCAA




UUGAAACUU GCCUGGGG













5644




CAUGCUCA CUGAUGA X GAA ACCCCACG




CCUGGGGUC UGAGCAUG













5661




UGUCUCCC CUGAUGA X GAA AUUCCCAU




AUGGGAAUA GGGAGACA













5674




CCCUUUCC CUGAUGA X GAA ACCCUGUC




GACAGGGUA GGAAACGG













5688




CUGAAGAG CUGAUGA X GAA AGGCGCCC




GGGCGCCUA CUCUUCAG













5691




ACCCUGAA CUGAUGA X GAA AGUAGGCG




CCCCUACUC UUCAGGGU













5693




AGACCCUG CUGAUGA X GAA AGAGUAGG




CCUACUCUU CAGGGUCU













5694




UAGACCCU CUGAUGA X GAA AAGAGUAG




CUACUCUUC AGGGUCUA













5700




GAUCUUUA CUGAUGA X GAA ACCCUGAA




UUCAGGGUC UAAAGAUC













5702




UUGAUCUU CUGAUGA X GAA AGACCCUG




CAGGGUCAA AAGAUCAA













5708




GCCCACUU CUGAUGA X GAA AUCUUUAG




CUAAAGAUC AAGUGGGC













5719




AGCGAUCC CUGAUGA X GAA AGGCCCAC




GUGGGCCUU GGAUCGCU













5724




AGCUUAGC CUGAUGA X GAA AUCCAAGG




CCUUGGAUC GCUAAGCU













5728




AGCCAGCU CUGAUGA X GAA ACCGAUCC




GGAUCGCUA AGCUGGCU













5737




AUCAAACA CUGAUGA X GAA AGCCAGCU




AGCUGGCUC UGUUUGAU













5741




UAGCAUCA CUGAUGA X GAA ACGAAGCC




GGCUCUGUU UGAUGCUA













5742




AUAGCAUC CUGAUGA X GAA AACAGAGC




CCUCUGUUU GAUGCUAU













5749




UGCAUAAA CUGAUGA X GAA AGCAUCAA




UUGAUGCUA UUUAUGCA













5751




CUUGCAUA CUGAUGA X GAA AUAGCAUC




GAUGCUAUU UAUGCAAG













5752




ACUUGCAU CUGAUGA X GAA AAUAGCAU




AUGCUAUUU AUGCAAGU













5753




AACUUGCA CUGAUGA X GAA AAAUAGCA




UGCUAUUUA UGCAAGUU













5761




UAGACCCU CUGAUGA X GAA ACUUGCAU




AUGCAAGUU AGGGUCCA













5762




AUAGACCC CUGAUGA X GAA AACAAGCA




UGCAAGUUA GGGUCUAU













5767




AAUACAAA CUGAUGA X GAA ACCCUAAC




GUUAGGGUC UAUGUAUU













5769




UAAAUACA CUGAUGA X GAA AGACCCUA




UAGGGUCUA UGUAUUUA













5773




AUCCUAAA CUGAUGA X GAA ACAUAGAC




GUCUAUGUA UUUAGGAU













5775




GCAUCCUA CUGAUGA X GAA AUACAUAG




CUAUGUAUU UAGGAUGC













5776




CGCAUCCU CUGAUGA X GAA AAUACAUA




UAUGUAUUU AGGAUGCG













5777




GCGCAUCC CUGAUGA X GAA AAAUACAU




AUGUAUUUA GGAUGCGC













5788




CUGAAGAG CUGAUGA X GAA AGGCGCAU




AUGCGCCUA CUCUUCAG













5791




ACCCUGAA CUGAUGA X GAA AGUACGGG




CGCCUACUC UUCAGGGU













5793




AGACCCUG CUGAUGA X GAA AGAGUAGG




CCUACUCUU CAGGGUCU













5794




UAGACCCU CUGAUGA X GAA AACAGUAG




CUACUCUUC AGGCUCCA













5800




GAUCUUUA CUGAUGA X GAA ACCCUGAA




UUCAGGGUC UAAAGAUC













5802




UUGAUCUU CUGAUGA X GAA AGACCCUG




CAGGGUCUA AAGAUCAA













5808




GCCCACUU CUGAUGA X GAA AUCUUUAG




CUAAAGAUC AAGUGGGC













5819




AGCGAUCC CUGAUGA X GAA AGGCCCAC




GUGGGCCUU GGAUCGCU













5824




AGCUUAGC CUGAUGA X GAA AUCCAAGG




CCUUGGAUC GCUAAGCU













5828




AGCCAGCU CUGAUGA X GAA AGCGAUCC




GGAUCGCUA AGCUGGCU













5837




AUCAAACA CUGAUGA X GAA AGCCAGCU




AGCUGGCUC UGUUUGAU













5841




UAGCAUCA CUGAUGA X GAA ACAGAGCC




GGCUCUGUU UGAUGCUA













5842




AUAGCAUC CUGAUGA X GAA AACAGACC




GCUCUGUUU GAUGCUAU













5849




UGCAUAAA CUGAUGA X GAA AGCAUCAA




UUGAUGCUA UUUAUGCA













5851




CUUGCAUA CUGAUGA X GAA AUAGCAUC




GAUGCUAUU UAUGCAAG













5852




ACUUGCAU CUGAUGA X GAA AAUAGCAU




AUGCUAUUU AUGCAAGU













5853




AACUUGCA CUGAUGA X GAA AAAUAGCA




UUGCAUUUA UGCAAGUU













5861




UAGACCCU CUGAUGA X GAA ACUUUCAU




AUGCAAGUU AGGGUCUA













5862




AUAGACCC CUGAUGA X GAA AACUUGCA




UGCAAGUUA GGGUCUAU













5867




AAUACAUA CUGAUGA X GAA ACCCUAAC




GUUAGGGUC UAUGUAUU













5869




UAAAUACA CUGAUGA X GAA AGACCCUA




UAGGGUCUA UGUAUUUA













5873




AUCCUAAA CUGAUGA X GAA ACAUAGAC




GUCUAUGUA UUUAGGAU













5875




ACAUCCUA CUGAUGA X GAA AUACAUAG




CUAUGUAUU UAGGAUGU













5876




GACAUCCU CUGAUGA X GAA AAUACAUA




UAUGUAUUU AGGAUGUC













5877




AGACAUCC CUGAUGA X GAA AAAUACAU




AUGUAUUUA GGAUGUCU













5884




AAGGUGCA CUGAUGA X GAA ACAUCCUA




UAGGAUGUC UGCACCUU













5892




GGCUGCAG CUGAUGA X GAA AGGUGCAG




CUGCACCUU CUGCAGCC













5893




UGGCUGCA CUGAUGA X GAA AAGGUGCA




UGCACCUUC UGCAGCCA













5904




CAGCUUCU CUGAUGA X GAA ACUGGCUG




CAGCCAGUC AGAAGCUG













5930




CAAGCAGC CUGAUGA X GAA AUCCACUG




CAGUGGAUU GCUGCUUC













5937




UCCCCAAG CUGAUGA X GAA AGCAGCAA




UUGCUGCUU CUUUGGGA













5938




CUCCCCAA CUGAUGA X GAA AAGCAGCA




UGCUGCUUC UUGGGGAG













5940




UUCUCCCC CUGAUGA X GAA AGAAGCAG




CUGCUUCUU GGGGAGAA













5953




AGGAAGCA CUGAUGA X GAA ACUCUUCU




AGAAGAGUA UGCUUCCU













5958




AUAAAAGG CUGAUGA X GAA AGCAAACU




AGGAUCCUU CCUUUUAU













5959




GAUAAAAG CUGAUGA X GAA AAGCAUAC




GUAUGCUUC AUUUUAUC













5962




AUGGAUAA CUGAUGA X GAA AGGAAGCA




UGCUUCCUU UUAUCCAU













5963




CAUGGAUA CUGAUGA X GAA AAGGAAGC




GCUUCCUUU UAUCCAUG













5964




ACAUGGAU CUGAUGA X GAA AAAGGAAG




CUUCCUUUU AUCCAUGU













5965




UACAUGGA CUGAUGA X GAA AAAAGGAA




UUCCUUUUA UCCAUGUA













5967




AUUACAUG CUGAUGA X GAA AUAAAAGG




CCUUUUAUC CAUGUAAU













5973




AGUUSSSU CUGAUGA X GAA ACAUGGAU




AUCCAUGUA AUUUAACU













5976




UACAGUUA CUGAUGA X GAA AUUACAUG




CAUGUAAUU UUACUGUA













5977




CUACACUU CUGAUGA X GAA AAUUACAU




AUGUAAUUU AACUGUAG













5978




UCUACAGU CUGAUGA X GAA AAAUUACA




UGUAAUUUA ACUGUAGA













5984




UCAGGUUC CUGAUGA X GAA ACACUUAA




UUAACUGUA GAACCUGA













5996




GUUACUUA CUGAUGA X GAA ACCUCAGG




CCUCAGCUC UAAGUAAC













5998




CGGUUACU CUGAUGA X GAA AGAGCUCA




UCAGCUCUA AGUAACCG













6002




UCUUCGGU CUGAUGA X GAA ACUUAGAG




CUCUAAGUA ACCGAAGA













6015




CAGAGGCA CUGAUGA X GAA ACAUUCUU




AAGAAUGUA UGCCUCUG













6021




UAAGAACA CUGAUGA X GAA AGGCAUAC




GUAUGCCUC UGUUCUUA













6025




CACAUAAG CUGAUGA X GAA ACAGAGGC




GCCUCUGUU CUUAUGUG













6026




GCACAUCA CUGAUGA X GAA AACAGAGG




CCUCUGUUC UUAUUUGC













6028




UGGCACAU CUGAUGA X GAA AGAACAGA




UCUGUUCUU AUGUGCCA













6029




GUGCCACA CUGAUGA X GAA AAGAACAG




CUGUUCUUA UGUGCCAC













6040




UAAACAAG CUGAUGA X GAA AUGUGGCA




UGCCACAUC CUUGUUUA













6043




CUUUAAAC CUGAUGA X GAA AGGAUGUG




CACAUCCUU GUUUAAAG













6046




AGCCUUCA CUGAUGA X GAA ACAAGGAU




AUCCUUGUU UAAAGGCU













6047




GAGCCUUU CUGAUGA X GAA AACAAGGA




UCCUUGUUU AAAGGCUC













6048




AGAGCCUU CUGAUGA X GAA AAACAAGG




CCUUGUUUA AAGGCUCU













6055




CAUACAGA CUGAUGA X GAA ACCCUUUA




UAAAGGCUC UCUGUAUG













6057




UUCAUACA CUGAUGA X GAA AGAGCCUU




AAGGCUCUC UGUAUGAA













6061




UCUCUUCA CUGAUGA X GAA ACAGAGAG




CUCUCUCUA UGAAGAGA













6079




GUGCUGAU CUGAUGA X GAA ACCCUCCC




GGGACCGUC AUCAGCAC













6082




AAUGUGCU CUGAUGA X GAA AUGACGGU




ACCGUCAUC AGCACAUU













6090




CACUAGGG CUGAUGA X GAA AUGUGCUG




CAGCACAUU CCCUAGUG













6091




UCACUAGG CUGAUGA X GAA AAUGUGCU




AGCACAUUC CCUAGUGA













6095




AGGCUCAC CUGAUGA X GAA AGGGAAUG




CAUUCCCCA GUGAGCCU













6104




GGAGCCAG CUGAUGA X GAA AGGCUCAC




GUGAGCCUA CUGGCUCC













6111




GCUGCCAG CUGAUGA X GAA AGCCAGGA




UACUGGCUC CUGGCAGC













6124




UUCCACAA CUGAUGA X GAA AGCCGCUG




CAGCGGCUU UUGUGGAA













6125




CUUCCACA CUGAUGA X GAA AAGCCGCU




AGCGGCUUU UGUCGAAG













6126




UCUUCCAC CUGAUGA X GAA AAAGCCGC




GCGGCUUUU GGGGAAGA













6137




UGGCUAGU CUGAUGA X GAA AGUCUUCC




GGAAGACUC ACUAGCCA













6141




CUUCUGGC CUGAUGA X GAA AGUGAGUC




GACUCACUA GCCAGAAG













6166




GUGGAGAG CUGAUGA X GAA ACUGUCCC




GGGACAGUC CUCUCCAC













6169




UUGGUGGA CUGAUGA X GAA AGGACUGU




ACAGUCCUC UCCACCAA













6171




UCUUGGUG CUGAUGA X GAA AGAGGACU




AGUCCUCUC CACCAAGA













6181




UGGAUUUA CUGAUGA X GAA AUCUUGGU




ACCAAGAUC UAAAUCCA













6183




UUUCGAUU CUGAUGA X GAA AGGUCUUG




CAAGAUCUA AAUCCAAA













6187




UUUGUUUG CUGAUGA X GAA AUUUAGAU




AUCUAAAUC CAAACAAA













6204




UCUGGCUC CUGAUGA X GAA AGCCUGCU




AGCAGGCUA GAGCCAGA













6226




ACAACAAA CUGAUGA X GAA AUUUGUCC




GGACAAAUC UUUGUUGU













6228




GAACAACA CUGAUGA X GAA AGAUUUGU




ACAAAUCUU UGUUGUUC













6229




GGAACAAC CUGAUGA X GAA AAGAUUUG




CAAAUCUUU GUUGUUCC













6232




AGAGGAAC CUGAUGA X GAA ACAAAGAU




AUCUUUGUU GUUCCUCU













6235




AGAAGAGG CUGAUGA X GAA ACAACAAA




UUUGUUGUU CCUCUUCU













6236




AAGAAGAG CUGAUGA X GAA AACAACAA




UUGUUGUUC CUCUUCUU













6239




GUAAAGAA CUGAUGA X GAA AGGAACAA




UUGUUCCUC UUCUUUAC













6241




GUGUAAAG CUGAUGA X GAA AGAGGAAC




GUUCCUCUU CUUUACAC













6242




UGUGUAAA CUGAUGA X GAA AAGAGGAA




UUCCUCUUC UUUACACA













6244




UAUGUAAA CUGAUGA X GAA AGAAGAGG




CCUCUUCUU UACACACA













6245




GUAUGUGU CUGAUGA X GAA AAGAAGAG




CUCUUCUUU ACACAUAC













6246




CGUAUGUG CUGAUGA X GAA AAAGAAGA




UCUUCUUUA CACAUACG













6252




GGUUUGCG CUGAUGA X GAA AUGUGUAA




UUACACAUA CGCAAACC













6280




AUUUAUAA CUGAUGA X GAA AUUGCCAG




CUGGCAAUU UUAUAAAU













6281




GAUUUAUA CUGAUGA X GAA AAUUGCCA




UGGCAAUUU UAUAAAUC













6282




UGAUUUAU CUGAUGA X GAA AAAUUGCC




GGCAAUUUU AUAAACCA













6283




CUGAUUUA CUGAUGA X GAA AAAAUUGC




GCAAUUUUA UAAAUCAG













6285




ACCUGAUU CUGAUGA X GAA AUAAAAUU




AAUUUUAUA AAUCAGGU













6289




AGUUACCU CUGAUGA X GAA AUUUAUAA




UUAUAAAUC AGGUAACU













6294




CUUCCAGU CUGAUGA X GAA ACCUGAUU




AAUCAGGUA ACUGGAAG













6308




CUGAGUUU CUGAUGA X GAA ACCUCCUU




AAGGAGGUU AAACUCAG













6309




UCUGAGUU CUGAUGA X GAA AACCUCCU




AGGAGGUUA AACUCAGA













6314




UUUUUUCU CUGAUGA X GAA AGUUUAAC




GUUAAACUC AGAAAAAA













6331




AAUUGACU CUGAUGA X GAA AGGUCUUC




GAAGACCUC AGUCAAUU













6335




AGAGAAUU CUGAUGA X GAA ACUGACGU




ACCUCAGUC AAUUCUCU













6339




AAGUAGAG CUGAUGA X GAA AUUGACUG




CAGUCAAUU CUCUACUU













6340




AAAGUAGA CUGAUGA X GAA AAUUGACU




AGUCAAUUC UCUACUUU













6342




AAAAAGUA CUGAUGA X GAA AGAAUUGA




UCAAUUCUC UACUUUUU













6344




AAAAAAAG CUGAUGA X GAA AGAGAAUU




AAUUCUCUA CUUUUUUU













6347




AAAAAAAA CUGAUGA X GAA AGUAGAGA




UCUCUACUU UUUUUUUU













6348




AAAAAAAA CUGAUGA X GAA AAGUAGAG




CUCUACUUU UUUUUUUU













6349




AAAAAAAA CUGAUGA X GAA AAAGUAGA




UCUACUUUU UUUUUUUU













6350




AAAAAAAA CUGAUGA X GAA AAAAGUAG




CUACUUUUU UUUUUUUU













6351




AAAAAAAA CUGAUGA X GAA AAAAAGUA




UACUUUUUU UUUUUUUU













6352




AAAAAAAA CUGAUGA X GAA AAAAAAGU




ACUUUUUUU UUUUUUUU













6353




AAAAAAAA CUGAUGA X GAA AAAAAAAG




CUUUUUUUU UUUUUUUU













6354




GAAAAAAA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UUUUUUUC













6355




GGAAAAAA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UUUUUUCC













6356




UGGAAAAA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UUUUUCCA













6357




UUGGAAAA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UUUUCCAA













6358




UUUGGAAA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UUUCCAAA













6359




AUUUGGAA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UUCCAAAU













6360




GAUUUGGA CUGAUGA X GAA AAAAAAAA




UUUUUUUUU UCCAAAUC













6361




UGAUUUGG CUGAUGA X GAA AAAAAAAA




UUUUUUUUU CCAAAUCA













6362




CUGAUUUG CUGAUGA X GAA AAAAAAAA




UUUUUUUUC CAAAUCAG













6368




UAUUAUCU CUGAUGA X GAA AUUUGGAA




UUCCAAAUC AGAUAAUA













6373




UGGGCUAU CUGAUGA X GAA AUCUGAUU




AAUCAGAUA AUAGCCCA













6376




UGCUGGGC CUGAUGA X GAA AUUAUCUG




CAGAUAAUA GCCCAGCA













6388




GUUAUCAC CUGAUGA X GAA AUUUGCUG




CAGCAAAUA GUGAUAAC













6394




UUAUUUGU CUGAUGA X GAA AUCACUUU




AUAGUGAUA ACAAAUAA













6401




UAAGGUUU CUGAUGA X GAA AUUUGUUA




UAACAAAUA AAACCUUA













6408




GAACAGCU CUGAUGA X GAA AGGUUUUA




UAAAACCUU AGCUGUUC













6409




UGAACAGC CUGAUGA X GAA AAGGUUUU




AAAACCUUA GCUGUUCA













6415




AAGACAUG CUGAUGA X GAA ACAGCUAA




UUAGCUGUU CAUGUCUU













6416




CAAGACAU CUGAUGA X GAA AACAGCUA




UAGCUGUUC AUGUCUUG













6421




GAAAUCAA CUGAUGA X GAA ACAUGAAC




GUUCAUGUC UUGAUUUC













6423




UUGAAAUC CUGAUGA X GAA AGACAUGA




UCAUGUCUU GAUUUCAA













6427




AUUAUUGA CUGAUGA X GAA AUGAAGAC




GUCUUGAUU UCAAUAAU













6428




AAUUAUUG CUGAUGA X GAA AAUCAAGA




UCUUGAUUU CAAUAAUU













6429




UAAUUAUU CUGAUGA X GAA AAAUCAAG




CUUGAUUUC AAUAAUUA













6433




GAAUUAAU CUGAUGA X GAA AUUGAAAU




AUUUCAAUA AUUAAUUC













6436




UAAGAAUU CUGAUGA X GAA AUUAUUGA




UCAAUAAUU AAUUCUUA













6437




UUAAGAAU CUGAUGA X GAA AAUUAUUG




CAAUAAUUA AUUCUUAA













6440




UGAUUAAG CUGAUGA X GAA AUUAAUUA




UAAUUAAUU CUUAAUCA













6441




AUGAUUAA CUGAUGA X GAA AAUUAAUU




AAUUAAUUC UUAAUCAU













6443




UAAUGAUU CUGAUGA X GAA AGAAUUAA




UUAAUUCUU AAUCAUUA













6444




UUAAUGAU CUGAUGA X GAA AAGAAUUA




UAAUUCUUA AUCAUUAA













6447




CUCUUAAU CUGAUGA X GAA AUUAAGAA




UUCUUAAUC AUUAAGAG













6450




GGUCUCUU CUGAUGA X GAA AUGAUUAA




UUAAUCAUU AAGAGACC













6451




UGGUCUCU CUGAUGA X GAA AAUGAUUA




UAAUCAUUA AGAGACCA













6461




GUAUUUAU CUGAUGA X GAA AUGGUCUC




GAGACCAUA AUAAAUAC













6464




GGAGUAUU CUGAUGA X GAA AUUAUGGU




ACCAUAAUA AAUACUCC













6468




AAAAGGAG CUGAUGA X GAA AUUUAUUA




UAAUAAAUA CUCCUUUU













6471




UGGAAAAG CUGAUGA X GAA AGUAUUUA




UAAAUACUC CUUUUCAA













6474




CUCUUGAA CUGAUGA X GAA AGGAGUAU




AUACUCCUU UUCAAGAG













6475




UCUCUUGA CUGAUGA X GAA AAGGAGUA




UACUCCUUU UAAAGAGA













6476




UUCUCUUG CUGAUGA X GAA AAAGGAGU




ACUCCUUUU CAAGAGAA













6477




UUUCUCUU CUGAUGA X GAA AAAAGGAG




CUCUUUUUC AAGAGAAA













6497




ACAAUUCU CUGAUGA X GAA AUGGUUUU




AAAACCAUU AGAAUUGU













6498




AACAAUUC CUGAUGA X GAA AAUGGUUU




AAACCAUUA GAAUUGUU













6503




UGAGUAAC CUGAUGA X GAA AUUCUAAU




AUUAGAAUU GUUACUCA













6506




AGCUGAGU CUGAUGA X GAA ACAAUUCU




AGAAUUGUU ACUCAGCU













6507




GAGCUGAG CUGAUGA X GAA AACAAUUC




GAAUUGUUA CUCAGCUC













6510




AAGGAGCU CUGAUGA X GAA AGUAACAA




UUGUUACUC AGCUCCUU













6515




GUUUGAAG CUGAUGA X GAA AGCUGAGU




ACUCAGCUC CUUCAAAC













6518




UGAGUUUG CUGAUGA X GAA AGGAGCUG




CAGCUCCUU CAAACUCA













6519




CUGAGUUU CUGAUGA X GAA AAGGAGCU




AGCUCCUUC AAACUCAG













6525




ACAAACCU CUGAUGA X GAA AGUUUGAA




UUCAAACUC AGGUUUGU













6530




AUGCUACA CUGAUGA X GAA ACCUGAGU




ACUCAGGUU UGUAGCAU













6531




UAUGCUAC CUGAUGA X GAA AACCUGAG




CUCAGGUUU GUAGCAUA













6534




AUGUAUGC CUGAUGA X GAA ACAAACCU




AGGUUUGUA GCAUACAU













6539




GACUCAUG CUGAUGA X GAA AUGCUACA




UGUAGCAUA CAUGAGUC













6547




GAAGGAUG CUGAUGA X GAA ACUCAUGU




ACAUGAGUC CAUCCAUC













6551




GACUGAUG CUGAUGA X GAA AUGGACUC




GAGUCCAUC CAUCAGUC













6555




CUUUGACU CUGAUGA X GAA AUGGAUGG




CCAUCCAUC AGUCAAAG













6559




CAUUCUUU CUGAUGA X GAA ACUGAUGG




CCAUCAGUC AAAGAAUG













6570




CCAGAUGG CUGAUGA X GAA ACCAUUCU




AGAAUGGUU CCAUCUGG













6571




UCCAGAUG CUGAUGA X GAA AACCAUUC




GAAUGGUUC CAUCUGGA













6575




AGACUCCA CUGAUGA X GAA AUGGAACC




GGUUCCAUC UGGAGUCU













6582




UACAUUAA CUGAUGA X GAA ACUCCAGA




UCUGGAGUC UUAAUGUA













6584




UCUACAUU CUGAUGA X GAA AGACUCCA




UGGAGUCUU AAUGUAGA













6585




UUCUACAU CUGAUGA X GAA AAGACUCC




GGAGUCUUA AUGUAGAA













6590




UUUCUUUC CUGAUGA X GAA ACAUUAAG




CUUAAUGUA GAAAGAAA













6609




AUUAUUAC CUGAUGA X GAA AGUCUCCA




UGGAGACUU GUAAUAAU













6612




CUCAUUUU CUGAUGA X GAA ACAAGUCU




AGACUUGUA AUAAUGAG













6615




UAGCUCAU CUGAUGA X GAA AUUACAAG




CUUGUAAUA AUGAGCUA













6623




UUUGUAAC CUGAUGA X GAA AGCUCAUU




AAUGAGCUA GUUACAAA













6626




CACUUUGU CUGAUGA X GAA ACUAGCUC




GAGCUAGUU ACAAAGUG













6627




GCACUUUG CUGAUGA X GAA AACUAGCU




AGCUAGUUA CAAAGUGC













6637




UAAUGAAC CUGAUGA X GAA AGCACUUU




AAAGUGCUU GUUCAUUA













6640




UUUUAAUG CUGAUGA X GAA ACAAGCAC




GUGCUUGUU CAUUAAAA













6641




AUUUUAAU CUGAUGA X GAA AACAAGCA




UGCUUGUUC AUUAAAAU













6644




GCUAUUUU CUGAUGA X GAA AUGAACAA




UUGUUCAUU AAAAUAGC













6645




UGCUAUUU CUGAUGA X GAA AAUGAACA




UGUUCAUUA AAAUAGCA













6650




UUCAGUGC CUGAUGA X GAA AUUUUAUU




AUUAAAAUA GCACUGAA













6662




CAUGUUUC CUGAUGA X GAA AUUUUCAG




CUGAAAAUU GAAACAUG













6674




UAUCAGUU CUGAUGA X GAA AUUCAUGU




ACAUGAAUU AACUGAUA













6675




UUAUCAGU CUGAUGA X GAA AAUUCAUG




CAUGAAUUA ACUGAUAA













6682




UGGAAUAU CUGAUGA X GAA AUCAGUUA




UAACUGAUA AUAUUCCA













6685




GAUUGGAA CUGAUGA X GAA AUUAUCAG




CUGAUAAUA UUCCAAUC













6687




AUGAUUGG CUGAUGA X GAA AUAUUAUC




GAUAAUAUU CCAAUCAU













6688




AAUGAUUG CUGAUGA X GAA AAUAUUAU




AUAAUAUUC CAAUCAUU













6693




UGGCAAAU CUGAUGA X GAA AUUGGAAU




AUUCCAAUC AUUUGCCA













6696




AAAUGGCA CUGAUGA X GAA AUGAUUGG




CCAAUCAUU UGCCAUUU













6697




UAAAUGGC CUGAUGA X GAA AAUGAUUG




CAAUCAUUU GCCAUUUA













6703




UUGUCAUA CUGAUGA X GAA AUGGCAAA




UUUGCCAUU UAUGACAA













6704




UUUGUCAU CUGAUGA X GAA AAUGGCAA




UUGCCAUUU AUGACAAA













6705




UUUUGCCA CUGAUGA X GAA AAAUGGCA




UGCCAUUUA UGACAAAA













6719




UUAGUGCC CUGAUGA X GAA ACCAUUUU




AAAAUGGUU CCCACUAA













6726




UUCUUUGU CUGAUGA X GAA AGUGCCAA




UUGGCACUA ACAAAGAA













6743




CUGAAAGG CUGAUGA X GAA AGUGCUCG




CGAGCACUU CCUUUCAG













6744




UCUGAAAG CUGAUGA X GAA AAGUGCUC




GAGCACUUC CUUUCAGA













6747




AACUCUGA CUGAUGA X GAA AGGAAGUG




CACUUCCUU UCAGAGUU













6748




AAACUCUG CUGAUGA X GAA AAGGAAGU




ACUUCCUUU CAGACUUU













6749




GAAACCCU CUGAUGA X GAA AAACGAAG




CUCCUUUUC AGAGUUUC













6755




AUCUCAGA CUGAUGA X GAA ACUCUGAA




UUCAGAGUU UCUGACAU













6756




UAUCUCAG CUGAUGA X GAA AACUCUGA




UCAGAGUUU CUGAGAUA













6757




UUAUCUCA CUGAUGA X GAA AAACUCUG




CAGAGUUUC UGAGAUAA













6764




ACGUACAU CUGAUGA X GAA AUCUCAGA




UCUGAGAAA AUGUACGU













6769




GUUCCACG CUGAUGA X GAA ACAUUAUC




GAUAAUGUA CGUGCAAC













6781




UCCACCCA CUGAUGA X GAA ACUGUUCC




GGAACAGUC UGGGUGGA













6814




AAGACACA CUGAUGA X GAA ACUUGCAC




GUGCAACUC UGUGUCUU













6820




ACUGACAA CUGAUGA X GAA ACACAGAC




GUCUGUGUC UUGUCAGU













6822




GGACUGAC CUGAUGA X GAA AGACACAG




CUGUGUCUU GUCAGUCC













6825




CUUGGACU CUGAUGA X GAA ACAAACCA




UGUCUUGUC AGUCCAAG













6829




ACUUCUUG CUGAUGA X GAA ACUGACAA




UUGUCAGUC CAAGAAGU













6851




CUAAAAUU CUGAUGA X GAA ACAUCUCG




CGAGAUGUU AAUUUUAG













6852




CCUAAAAU CUGAUGA X GAA AACAUCCC




GAGAUGUUA AUUUUAGG













6855




GUCCCUAA CUGAUGA X GAA AUUAACAU




AUGUUAAUU UUAGGGAC













6856




GGUCCCUA CUGAUGA X GAA AAUUAACA




UGUUAAUUU UAGGGACC













6857




GGGUCCCU CUGAUGA X GAA AAAUUAAC




GUUAAUUUU AGGGACCC













6858




CGGGUCCC CUGAUGA X GAA AAAAUUAA




UUAAUUUUA GGGACCCG













6872




UAGGGAAC CUGAUGA X GAA AGGCACGG




CCGUGCCUU GUUUCCUA













6875




GGCUAGGA CUGAUGA X GAA ACAACGCA




UGCCUUGUU UCCUAGCC













6876




GGGCUAGG CUGAUGA X GAA AACAAGGC




GCCUUGUUU CCUAGCCC













6877




UGGGCUAG CUGAUGA X GAA AAACAAGG




CCUUGUUUC CUCGCCCA













6880




UUGUGGGC CUGAUGA X GAA AGGAAACA




UGUUUCCUA GCCCACAA













6901




AUCUGUUU CUGAUGA X GAA AUGUUUGC




GCAAACAUC AAACAGAU













6910




CUAGCGAG CUGAUGA X GAA AUCUGUUU




AAACAGAUA CUCGCUAG













6913




AGGCUAGC CUGAUGA X GAA AGUGUCUC




CAGAUACUC GCUAGCCU













6917




AAUGAGGC CUGAUGA X GAA AGCGAGUA




UACUCGCUA GCCUCAUU













6922




AUUUAAAU CUGAUGA X GAA AGGCUAGC




GCUAGCCUC AUUUAAAU













6925




UCAAUUUA CUGAUGA X GAA AUGAGGCU




AGCCUCAUU UAAAUUGA













6926




AUCAAUUU CUGAUGA X GAA AAUGAGGC




GCCUCAUUU AAAUUGAU













6927




AAUCAAUU CUGAUGA X GAA AAAUGAGG




CCUCAUUUA AAUUGAUU













6931




CUUUAAUC CUGAUGA X GAA AUUUAAAU




AUUUAAAUU GAUUAAAG













6935




CCUCCUUU CUGAUGA X GAA AUCAAUUU




AAAUUGAUU AAAGGAGG













6936




UCCUCCUU CUGAUGA X GAA AAUCAAUU




AAUUGAUUA AAGGAGGA













6951




CGGCCAAA CUGAUGA X GAA AAGCACUC




GAGUGCAUC UUUGGCCG













6953




GUCGGCCA CUGAUGA X GAA AGAUGCAC




GUGCAUCUU UGGCCGAC













6954




UGUCGGCC CUGAUGA X GAA AAGAUGCA




UGCAUCUUU GGCCGACA













6970




CACACAGU CUGAUGA X GAA ACACCACU




AGUGGUGUA ACUGUGUG













7026




AACACACA CUGAUGA X GAA ACACCCAC




GUGGGUGUA UGUGUGUU













7034




AUGCACAA CUGAUGA X GAA ACACACAU




AUGUGUGUU UUGUGCAU













7035




UAUGCACA CUGAUGA X GAA AACACACA




UGUGUGUUU UGUGCAUA













7036




UAUGCACA CUGAUGA X GAA AAACACAC




GUGUGUUUU GUGCAUAA













7043




UAAAUAGU CUGAUGA X GAA AUGCACAA




UUGUGCAUA ACUAUUUA













7047




UCCUUAAA CUGAUGA X GAA AGUUAUGC




GCAUAACUA UUUAAGGA













7049




UUUCCUUA CUGAUGA X GAA AUAGUGAU




AUAACUAUU UAAGGAAA













7050




GUUUCCUU CUGAUGA X GAA AAUAGUUA




UAACUAUUU AGGGAAAC













7051




AGUUUCCU CUGAUGA X GAA AAAUAGUU




AACCAUUUA AAGAAACU













7065




AACUUUAA CUGAUGA X GAA AUUCCAGU




ACUGGAAUU UUAAAGUU













7066




UAACUUAA CUGAUGA X GAA AAUUCCAG




CUGGAAUUU UAAAGUUA













7067




GUAACUUU CUGAUGA X GAA AAAUUCCA




UGGAAUUUU AAAGUUAC













7068




AGGAACUU CUGAUGA X GAA AAAAUUCC




GGAAUUUUA AAGUUACU













7073




AUAAAAGU CUGAUGA X GAA ACUUUAAA




UUUAAAGUU ACUUUUAU













7074




UAUAAAAG CUGAUGA X GAA AACUUUAA




UUAAAGUUA CUUUUAUA













7077




UUGUAUAA CUGAUGA X GAA AGUAACUU




AAGUUACUU UUAUACAA













7078




UUUGUAUA CUGAUGA X GAA AAGUAACU




AGUUACUUU UAUACAAA













7079




GUUUGUAU CUGAUGA X GAA AAAGUAAC




GUUACUUUU AUACAAAC













7080




GGUUUGUA CUGAUGA X GAA AAAAGUAA




UUACUUUUA UACAAACC













7082




UUGGUUUG CUGAUGA X GAA AUAAAAGU




ACUUUCAUA CAAACCAA













7095




GUAGCUUA CUGAUGA X GAA AUUCUUGG




CCAAGAAUA UAUGCUAC













7097




CUGUAGCA CUGAUGA X GAA AUAUUCUU




AAGAAUAUA UGCUACAG













7102




UAUAUCUG CUGAUGA X GAA AGCAUAUA




UAUAUGCUA CAGAUAUA













7108




CUGUCUUA CUGAUGA X GAA AUCUGUAG




CUACAGAUA UAAGACAG













7110




GCCUGUCU CUGAUGA X GAA AUAUCUGU




ACAGAUAUA AGACAGAC













7124




UAGGACCA CUGAUGA X GAA ACCAUGCC




GACAUGGUU UGGUCCUA













7125




AUAGGACC CUGAUGA X GAA AACCAUGU




ACAUGGUUU GCUCUUAU













7129




AAAUAUAG CUGAUGA X GAA ACCAAACC




GGUUUGGUC CUAUAUUU













7132




UAGAAAUA CUGAUGA X GAA AGGACCAA




UUGGUCCUA UAUUUCUA













7134




ACUAGAAA CUGAUGA X GAA AUAGGACC




GGUCCUAUA UUUCUAGU













7136




UGACUAGA CUGAUGA X GAA AUAUAGGA




UCCUAUAUU UCUAGUCA













7137




AUGACUAG CUGAUGA X GAA AAUAUAGG




CCUAUAUUU CUAGUCAU













7138




CAUGACUA CUGAUGA X GAA AAAUAUAG




CUAUAUUUC UAGUCAUG













7140




AUCAUGAC CUGAUGA X GAA AGAAAUAU




AUAUUUCUA GUCAUGAU













7143




UUCAUCAU CUGAUGA X GAA ACUAGAAA




UUUCUAGUC AUGAUGAA













7155




AUACAAAA CUGAUGA X GAA ACAUUCAU




AUGAAUGUA UUUUGUAU













7157




GUAUACAA CUGAUGA X GAA AUACAUUC




GAAUGUAUU UUGUAUAC













7158




GGUAUACA CUGAUGA X GAA AAUACAUU




AAUGUAUUU UGUAUACC













7159




UGGUAUAC CUGAUGA X GAA AAAUACAU




AUGUAUUUU GUAUACCA













7162




AGAUGGUA CUGAUGA X GAA ACAAAAUA




UAUUUUGUA UACCAUCU













7164




GAAGAUGG CUGAUGA X GAA AUACAAAA




UUUUGUAUA CCAUCUUC













7169




UAUAUGAA CUGAUGA X GAA AUGGUAUA




UAUACCAUC UUCAUAUA













7171




AUUAUAUG CUGAUGA X GAA AGAUGGUA




UACCAUCUU CAUAUAAU













7172




UAUUAUAU CUGAUGA X GAA AAGAUGGU




ACCAUCUUC AUAUAAUA













7175




GUAUAUUA CUGAUGA X GAA AUGAAGAU




AUCUUCAUA UAAUAUAC













7177




AAGUAUAU CUGAUGA X GAA AUAUGAAG




CUUCAUAUA AUAUACUU













7180




UUUAAGUA CUGAUGA X GAA AUUAUAUG




CAUAUAAUA UACUUAAA













7182




UUUUUAAG CUGAUGA X GAA AUAUUAUA




UAUAAUAUA CUUAAAAA













7185




AUAUUUUU CUGAUGA X GAA AGUAUAUU




AAUAUACUU AAAAAUAU













7186




AAUAUUUU CUGAUGA X GAA AAGUAUAU




AUAUACUUA AAAAUAUU













7192




UUAAGAAA CUGAUGA X GAA AUUUUUAA




UUAAAAAUA UUUCUUAA













7194




AAUUAAGA CUGAUGA X GAA AUAUUUUU




AAAAAUAUU UCUUAAUU













7195




CAAUUAAG CUGAUGA X GAA AAUAUUUU




AAAAUAUUU CUUAAUUG













7196




CCAAUUAA CUGAUGA X GAA AAAUAUUU




AAAUAUUUC UUAAUUGG













7198




UCCCAAUU CUGAUGA X GAA AGAAAUAU




AUAUUUCUU AAUUGGGA













7199




AUCCCAAU CUGAUGA X GAA AAGAAAUA




UAUUUCUUA AUUGGGAU













7202




CAAAUCCC CUGAUGA X GAA AUUAAGAA




UUCUUAAUU GGGAUUUG













7208




CGAUUACA CUGAUGA X GAA AUCCCAAU




AUUGGGAUU UGUAAUCG













7209




ACGAUUAC CUGAUGA X GAA AAUCCCAA




UUGGGAUUU GUAAUCGU













7212




GGUACGAU CUGAUGA X GAA ACAAAUCC




GGAUUUGUA AUCGUACC













7215




GUUGGUAC CUGAUGA X GAA AUUACAAA




UUUGUAAUC GUACCAAC













7218




UAAGUUCG CUGAUGA X GAA ACGAUUAC




GUAAUCGUA CCAACUUA













7225




UAUCAAUU CUGAUGA X GAA AGUUGGUA




UACCAACUU AAUUGAUA













7226




UUAUCAAU CUGAUGA X GAA AAGUUGGU




ACCAACUUA AUUGAUAA













7229




AGUUUAUC CUGAUGA X GAA AUUAAGUU




AACUUAAUU GAUAAACU













7233




GCCAAGUU CUGAUGA X GAA AUCAAUUA




UAAUUGAUA AACUUGGC













7238




CAGUUGCC CUGAUGA X GAA AGUUUAUC




GAUAAACUU GGCAACUG













7249




GAACAUAA CUGAUGA X GAA AGCAGUUG




CAACUGCUU UUAUGUUC













7250




AGAACAUA CUGAUGA X GAA AAGCAGUU




AACUGCUUU UAUGUUCU













7251




CAGAACAU CUGAUGA X GAA AAAGCAGU




ACUGCUUUU AUUUUCUG













7252




ACAGAACA CUGAUGA X GAA AAAAGCAG




CUGCUUUUA UGUUCUGU













7256




GAAGACAG CUGAUGA X GAA ACAUAAAA




UUUUAUGUU CUGUCUCC













7257




AAGAGACA CUGAUGA X GAA AACAUAAA




UUUAUGUUC UGUCUCCU













7261




UGGAAGGA CUGAUGA X GAA ACAGAACA




UGUUCUGUC UCCUUCCA













7263




UAUGGAAG CUGAUGA X GAA AGACAAAA




UUCUGUCUC CUUCCAUA













7266




AUUUAUGG CUGAUGA X GAA AGGAGACA




UGUCUCCUU CCAUAAAU













7267




AAUUUAUG CUGAUGA X GAA AAGGAGAC




GUCUCCUUC CAUAAAUU













7271




GAAAAAUU CUGAUGA X GAA AUGGAAGG




CCUUCCAUA AAUUUUUC













7275




UUUUGAAA CUGAUGA X GAA AUUUAUGG




CCAUAAAUU UUUCAAAA













7276




AUUUUGAA CUGAUGA X GAA AAUUUAUG




CAUAAAUUU UUCAAAAU













7277




UAUUUUGA CUGAUGA X GAA AAAUUUAU




AUAAAUUUU UCAAAAUA













7278




GUAUUUUG CUGAUGA X GAA AAAAUUUA




UAAAUUUUU CAAAAUAC













7279




AGUAUUUU CUGAUGA X GAA AAAAAUUU




AAAUUUUUC AAAAUACU













7285




UGAAUUAG CUGAUGA X GAA AUUUUGAA




UUCAAAAUA CUAAUUCA













7288




UGUUGAAU CUGAUGA X GAA AGUAUUUU




AAAAUACUA AUUCAACA













7291




CUUUGUUG CUGAUGA X GAA AUUAGUAU




AUACUAAUU CAACAAAG













7292




UCUUUCUU CUGAUGA X GAA AAUUAGUA




UACUAAUUC AACAAAGA













7308




AAAAAAAA CUGAUGA X GAA AGCUUUUU




AAAAAGCUC UUUUUUUU













7310




GGAAAAAA CUGAUGA X GAA AGAGCUUU




AAAGCUCUU UUUUUUCC













7311




AGGAAAAA CUGAUGA X GAA AAGAGCUU




AAGCUCUUU UUUUUCCU













7312




UAGGAAAA CUGAUGA X GAA AAAGAGCU




AGCUCUUUU UUUUCCUA













7313




UUAGGAAA CUGAUGA X GAA AAAAGAGC




GCUCUUUUU UUUCCUAA













7314




UUUAGGAA CUGAUGA X GAA AAAAAGAG




CUCUUUUUU UUCCUAAA













7315




UUUUAGGA CUGAUGA X GAA AAAAAAGA




UCUUUUUUU UCCCAAAA













7316




AUUUUAGG CUGAUGA X GAA AAAAAAAG




CUUUUUUUU CCUAAAAU













7317




UAUUUUAG CUGAUGA X GAA AAAAAAAA




UUUUUUUUC CUAAAAUA













7320




GUUUAUUU CUGAUGA X GAA AGGAAAAA




UUUUUCCUA AAAUAAAC













7325




UUUGAGUU CUGAUGA X GAA AUUUUAGG




CCUAAAAUA AACUCAAA













7330




AUAAAUUU CUGAUGA X GAA AGUUUAUU




AAUAAACUC AAAUUUAU













7335




CAAUGAUA CUGAUGA X GAA AUUUGAGU




ACUCAAAUU UAUCCUUG













7336




ACAAGGAU CUGAUGA X GAA AAUUUAAG




CUCAAAUUU AUCCUUGU













7337




AACAAGGA CUGAUGA X GAA AAAUUUGA




UCAAADUUA UCCUUGUU













7339




UAAACAAG CUGAUGA X GAA AUAAAUUU




AAAUUUAUC CUUGUUUA













7342




CCCUAAAC CUGAUGA X GAA AGGAUAAA




UUUAUCCUU GUUUAGAG













7345




CUGCUCUA CUGAUGA X GAA ACAAGGAU




AUCCUUGUU UAGAGCAG













7346




UCUGCUCU CUGAUGA X GAA AACAAGGA




UCCUUGUUU AGAGCAGA













7347




CUCUGCUC CUGAUGA X GAA AAACAAGG




CCUUGUUUA GAGCAGAG













7362




UUUUUCUU CUGAUGA X GAA AUUUUUCU




AGAAAAAUU AAGAAAAA













7363




GUUUUUCU CUGAUGA X GAA AAUUUUUC




GAAAAAUUA AGAAAAAC













7373




CCAUUUCA CUGAUGA X GAA AGUUUUUC




GAAAAACUU UGAAAUGG













7374




ACCAUUUC CUGAUGA X GAA AAGUUUUU




AAAAACUUU GAAAUGGU













7383




UUUUUUGA CUGAUGA X GAA ACCAUUUC




GAAAUGGUC UCAAAAAA













7385




AAUUUUUU CUGAUGA X GAA AGACCAUU




AAUGGUCUC AAAAAAUU













7393




UAUUUAGC CUGAUGA X GAA AUUUUUUG




CAAAAAAUU GCUAAAUA













7397




AAAAUAUU CUGAUGA X GAA AGCAAUUU




AAAUUGCUA AAUAUUUU













7401




AUUGAAAA CUGAUGA X GAA AUUUAGCA




UGCUAAAUA UUUUCAAU













7403




CCAUUGAA CUGAUGA X GAA AUAUUUAG




CUAAAUAUU UUCAAUGG













7404




UCCAUUGA CUGAUGA X GAA AAUAUUUA




UAAAUAUUU UCAAUGGA













7405




UUCCAUUG CUGAUGA X GAA AAAUAUUU




AAAUAUUUU CAAUGGAA













7406




UUUCCAUU CUGAUGA X GAA AAAAUAUU




AAUAUUUUC AAUGGAAA













7418




CUAACAUU CUGAUGA X GAA AGUUUUCC




GGAAAACUA AAUGUUAG













7424




GCUAAACU CUGAUGA X GAA ACAUUUAG




CUAAAUGUU AGUUUAGC













7425




AGCUAAAC CUGAUGA X GAA AACAUUUA




UAAAUGUUA GUUUAGCU













7428




AUCAGCUA CUGAUGA X GAA ACUAACAU




AUGUUAGUU UAGCUGAU













7429




AAUCAGCU CUGAUGA X GAA AACUAACA




UGUUAGUUU AGCUGAUU













7430




CAAUCAGC CUGAUGA X GAA AAACUAAC




GUUAGUUUA GCUGAUUG













7437




CCCCAUAC CUGAUGA X GAA AUCACCCA




UAGCUGAUU GUAUGGGG













7440




AAACCCCA CUGAUGA X GAA ACAAUCAG




CUGAUUGUA UGGGGUUU













7447




GGUUCGAA CUGAUGA X GAA ACCCCAUA




UAUGGGGUU UUCGAACC













7448




AGGUUCGA CUGAUGA X GAA AACCCCAU




AUGGGGUUU UCGAACCU













7449




AAGGUUCG CUGAUGA X GAA AAACCCCA




UGGGGUUUU CGAACCUU













7450




AAAGGUUC CUGAUGA X GAA AAAACCCC




GGGGUUUUC GAACCUUU













7457




AAAAGUGA CUGAUGA X GAA AGGUUCGA




UCGAACCUU UCACUUUU













7458




AAAAAGUG CUGAUGA X GAA AAGGUUCG




CGAACCUUU CACUUUUU













7459




CAAAAAGU CUGAUGA X GAA AAAGGUUC




GAACCUUUC ACUUUUUG













7463




CAAACAAA CUGAUGA X GAA AGUGAAAG




CUUUCACUU UUUGUUUG













7464




ACAAACAA CUGAUGA X GAA AAGUGAAA




UUUCACUUU UUGUUUGU













7465




AACAAACA CUGAUGA X GAA AAAGUGAA




UUCACUUUU UGUUUGUU













7466




AAACAAAC CUGAUGA X GAA AAAAGUGA




UCACUUUUU GUUUGUUU













7469




GUAAAACA CUGAUGA X GAA ACAAAAAG




CUUUUUGUU UGUUUUAC













7470




GGUAAAAC CUGAUGA X GAA AACAAAAA




UUUUUGUUU GUUUUACC













7473




AUAGGUAA CUGAUGA X GAA ACAAACAA




UUGUUUGUU UUACCUAU













7474




AAUAGAAA CUGAUGA X GAA AACAAACA




UGUUUGUUU UACCUAUU













7475




AAAUAGGU CUGAUGA X GAA AAACAAAC




GUUUGUUUU ACCUAUUU













7476




GAAAUAGG CUGAUGA X GAA AAAACAAA




UUUGUUUUA CCUAUUUC













7480




UUGUGAAA CUGAUGA X GAA AGGUAAAA




UUUUACCUA UUUCACAA













7482




AGUUGUGA CUGAUGA X GAA AUAGGUAA




UUACCUAUU UCACAACU













7483




CAGUUGUG CUGAUGA X GAA AAUAGGUA




UACCUAUUU CACAACAG













7484




ACAGUUGU CUGAUGA X GAA AAAUAGGU




ACCUAUUUC ACAACUGU













7495




UGGCAAUU CUGAUGA X GAA ACACAGUU




AACUGUGUA AAUUGCCA













7499




UUAUUGGC CUGAUGA X GAA AUUUACAC




GUGUAAAUU GCCACCAA













7506




ACAGGAAU CUGAUGA X GAA AUUGGCAA




UUGCCAAUA AUUCCUGU













7509




UGGACAGG CUGAUGA X GAA AUUAUUGG




CCAAUAAUU CCUGUCCA













7510




AUGGACAG CUGAUGA X GAA AAUUAUUG




CAAUAAUUC CUGUCCAU













7515




UUUUCAUG CUGAUGA X GAA ACAGGAAU




AUUCUUGUC CAUGAAAA













7531




CACUGGAU CUGAUGA X GAA AUUUGCAU




AUGCAAAUU AUCCAGUG













7532




ACACUGGA CUGAUGA X GAA AAUUUGCA




UGCAAAUUA UCCAGUGU













7534




CUACACUG CUGAUGA X GAA AUAAUUUG




CAAAUUAUC CAGUGUAG













7541




AAUAUAUC CUGAUGA X GAA ACACUGGA




UCCAGUGUA GAUAUAUU













7545




GUCAAAUA CUGAUGA X GAA AUCUACAC




GUGUAGAUA UAUUUGAC













7547




UGGUCAAA CUGAUGA X GAA AUAUCUAC




GUAGAUAUA UUUCACCA













7549




GAUGGUCA CUGAUGA X GAA AUAUAUCU




AGAUAUAUU UGACCAUC













7550




UGAUGGUC CUGAUGA X GAA AAUAUAUC




GUAUAUUUU GACCAUCA













7557




CAUAGGGU CUGAUGA X GAA AUGGUCAA




UUGACCAUC ACCCUAUG













7563




AAUACCCA CUGAUGA X GAA AGGGUGAU




AUCACCCUA UGGAUAUU













7569




CUAGCCAA CUGAUGA X GAA AUCCAUAG




CUAUGGAUA UUGGCUAG













7571




AACUAGCC CUGAUGA X GAA AUAUCCAU




AUGGAUAUU GGCUAGUU













7576




GGCAAAAC CUGAUGA X GAA AGCCAAUA




UAUUGGCUA GUUUUGCC













7579




AAAGGCAA CUGAUGA X GAA ACUAGUCA




UGGCUAGUU UUGCCUUU













7580




UAAAGCCA CUGAUGA X GAA AACUAGCC




GGCUAGUUU UGCCUUUA













7581




AUAAAGGC CUGAUGA X GAA AAACUAGC




GCUAGUUUU GCCUUUAU













7586




GCUUAAUA CUGAUGA X GAA AGGCAAAA




UUUUGCCUU UAUUAAGC













7587




UGCUUAAU CUGAUGA X GAA AAGGCAAA




UUUGCCUUU AUUAAGCA













7588




UUGCUUAA CUGAUGA X GAA AAAGGCAA




UUGCCUUUA UUAAGCAA













7590




AUUUGCUU CUGAUGA X GAA AUAAAGGC




GCCUUUAUU AAGCAAAU













7591




AAUUUGCU CUGAUGA X GAA AAUAAAGG




CCUUUAUUA AGCAAAUU













7599




CUGAAAUG CUGAUGA X GAA AUUUGCUU




AAGCAAAUU CAUUUCAG













7600




GCUGAAAU CUGAUGA X GAA AAUUUGCU




AGCAAAUUC AUUUCAGC













7603




CAGGCUGA CUGAUGA X GAA AUGAAUUU




AAAUUCAUU UCAGCCUG













7604




UCACGGUG CUGAUGA X GAA AAUGAAUU




AAUUCAUUU CAGCCUGA













7605




UUCAGGCU CUGAUGA X GAA AAAUGAAU




AUUCAUUUC AGCCUGAA













7617




UAUAGGCA CUGAUGA X GAA ACAUUCAG




CUGAAUGUC UGCCUAUA













7623




AGAAUAUA CUGAUGA X GAA ACGCAGAC




GUCUGCCUA UAUAUUCU













7625




AGAGAAUA CUGAUGA X GAA AUAGGCAG




CUGCCUAUA UAUUCUCU













7627




GCAGAGAA CUGAUGA X GAA AUAUAGGC




GCCUAUAUA UCCUCUCC













7629




GAGCAGAG CUGAUGA X GAA AUAUAUAG




CUAUAUAUU CUCUGCUC













7630




AGAGCAGA CUGAUGA X GAA AAUAUAUA




UAUAUAUUC UCUGCUCU













7632




AAAGACCA CUGAUGA X GAA AGAAUAUA




UAUAUUCUC UGCUCUUU













7637




AAUACAAA CUGAUGA X GAA ACCAGAGA




UCUCUGCUC UUUGUAUU













7639




AGAAUACA CUGAUGA X GAA AGAGCAGA




UCUGCUCUU UCUAUUCU













7640




GAGAAUAC CUGAUGA X GAA AAGAGCAG




CUGCUCUUU GUAUUCUC













7643




AAGGAGAA CUGAUGA X GAA ACAAACAG




CUCUUUGUA UUCUCCUU













7645




CAAACCAG CUGAUGA X GAA AUACAAAG




CUUUGUAUU CUCCUUUG













7646




UCAAAGGA CUGAUGA X GAA AAUACAAA




UUUGUAUUC UCCUUUGA













7648




CUUCAAAG CUGAUGA X GAA AGAAUACA




UUUUUUCUC CUUUGAAC













7651




CGGGUUCA CUGAUGA X GAA AGGAGAAU




AUUCUCCUU UGAACCCG













7652




ACGGGUUC CUGAUGA X GAA AAGGAGAA




UUCUCCUUU GAACCCGU













7661




GAUGUUUU CUGAUGA X GAA ACGGGUUC




GAACCCGUU AAAACAUC













7662




GGAUGUUU CUGAUGA X GAA AACGGGUU




AACCCGUUA AAACAUCC













7669




UGCCACAG CUGAUGA X GAA AUGUUUUA




UAAAACAUC CUGUGGCA











Where “X” represents stem II region of a HH ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20 3252). The length of stem II may be ≧ 2 base-pairs.





















TABLE III











Human fLt1 VEGF Receptor-Hairpin Ribozyme and Substrate sequence













nt.








Position




HP Ribozyme Sequence




Substrate









  16




CGGGGAGG AGAA GAGAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUCUCG GCU CCUCCCCG













  39




CCGCUCCG AGAA GCCGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCGGCG GCU CGGAGCGG













 180




CCGCCAGA AGAA GUCCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAGGACG GAC UCUGGCGG













 190




AACGACCC AGAA GCCAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUGGCG GCC GGGUCGUU













 278




GCGCGCAC AGAA GGACCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGGUCCU GCU GUGCGCGC













 290




GACAGCUG AGAA GCGCGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCGCGCU GCU CAGCUGUC













 295




AAGCAGAC AGAA GAGCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGCUCA GCU GUCUGCUU













 298




GAGAAGCA AGAA GCUGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCAGCU GUC UGCUUCUC













 302




CUGUGAGA AGAA GACAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUGUCU GCU UCUCACAG













 420




CAUUUAUG AGAA GCUUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAAGCA GCC CAUAAAUG













 486




CUUCCACA AGAA GAUUUA ACCAGACAAACACACGUUGUGGUACAUUACCUGGUA




UAAAUCU GCC UGUGGAAG













 537




UUUGCUUG AGAA GUGUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAACACA GCU CAAGCAAA













 565




AUAUUUGC AGAA GUAGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUCUACA GCU GCAAAUAU













 721




CGUAACCC AGAA GGGAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUUCCCU GCC GGGUUACG













 786




CGUUUUCC AGAA GGGAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAUCCCU GAU GGAAAACG













 863




CUUCACAG AGAA GAAGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCUUCU GAC CUGUGAAG













1056




UUUUUUUC AGAA GGGUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUACCCU GAU GAAAAAAA













1301




GCCGGUAA AGAA GCUUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCAAGCG GUC UUACCGGC













1310




UCAUAGAG AGAA GGUAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUACCG GCU CUCUAUGA













1389




AAAUAGCG AGAA GAUUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAAAUCU GCU CGCUAUUU













1535




UUUCGUAA AGAA GGGGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AACCCCA GAU UUACGAAA













1566




AGAGCCGG AGAA GGAAAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUUUCCA GAC CCGGCUCU













1572




GGGUAGAG AGAA GGGUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGACCCG GCU CUCUACCC













1604




CGGUACAA AGAA GGAUUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAAUCCU GAC UUGUACCG













1824




AUUCUAGA AGAA GCCACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUGGCU GAC UCUAGAAU













1908




UUUGGCAC AGAA GUGAUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UAUCACA GAU GUGCCAAA













1949




CUCCUUCC AGAA GCAUUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAAUGCC GAC GGAAGGAG













1973




CUGUGCAA AGAA GUUUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAAACU GUC UUGCACAG













2275




AGUGGUGG AGAA GCUGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUCAGCA GUU CCACCACU













2321




ACCAAGUG AGAA GAGGCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGCCUCA GAU CACUUGGU













2396




UUUCAAUA AGAA GCGUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCACGCU GUU UAUUGAAA













2490




GUUCCUUG AGAA GUGAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUCACU GUU CAAGGAAC













2525




UUAGAGUG AGAA GCUCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGAGCU GAU CACUCUAA













2625




GAUAGGUA AGAA GUCUUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAAGACU GAC UACCUAUC













2652




GGAACUUC AGAA GGGUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGACCCA GAU GAAGUUCC













2684




CAUAAGGG AGAA GCUCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUGAGCG GCU CCCUUAUG













2816




CAGCCACA AGAA GGCACG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CGUGCCG GAC UGUGGCUG













2873




GCUCAGUC AGAA GAGCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGCUCU GAU GACUGAGC













2930




AGGCUCCC AGAA GGUUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUAACCU GCU GGGAGCCU













2963




CAAUCACC AGAA GAGGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCCUCU GAU GGUGAUUG













3157




UUCCUGAA AGAA GGAGCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGCUCCG GCU UUCAGGAA













3207




UAGAAACC AGAA GAAUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAUUCU GAC GGUUUCUA













3211




CUUGUAGA AGAA GUCAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUGACG GUU UCUACAAG













3245




UGUAAGAA AGAA GAUCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGAUCU GAU UUCUUACA













3256




CACUUGAA AGAA GUAAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUUACA GUU UUCAAGUG













3287




UUCUGGAA AGAA GCAACU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGUUCCU GUC UUCCAGAA













3402




CUCACAUA AGAA GGGUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAACCCC GAU UAUGUGAG













3580




CCUCAGGC AGAA GCAAAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUUUGCA GUC GCCUGAGG













3641




CCAGCAUG AGAA GAUAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUAUCA GAU CAUGCUGG













3655




UCUGUGCC AGAA GUCCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGGACU GCU GGCACAGA













3810




UCAGAGAA AGAA GGAGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AACUCCU GCC UUCUCUGA













3846




AACUUCGG AGAA GAAAUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UAUUUCA GCU CGGAAGUU













3873




CUGACAUC AGAA GAGCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGCUCU GAU GAUGUCAG













3995




GAGAGGCC AGAA GAGUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCACUCU GUU GGCCUCUC













4100




UGACAUCA AGAA GCCCCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CGGGGCU GUC UGAUGUCA













4104




CUGCUGAC AGAA GACAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUGUCU GAU GUCAGCAG













4120




AUGGCAGA AGAA GGGCCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGGCCCA GUU UCUGCCAU













4135




GUGCCCAC AGAA GGAAUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAUUCCA GCU GUGGGCAC













4210




GGGCGGGG AGAA GCACGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCGUGCU GCU CCCCGCCC













4217




AGUCUGGG AGAA GGGAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUCCCC GCC CCCAGACU













4224




GAGUUGUA AGAA GGGGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCCCCCA GAC UACAACUC













4382




CAAAAAGC AGAA GGCUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAGCCA GCU GCUUUUUG













4385




UCACAAAA AGAA GCUGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCCAGCU GCU UUUUGUGA













4537




GGGGUUGG AGAA GGGAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUCCCU GCU CCAACCCC













4573




CUCAAUCA AGAA GGUCCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGGACCA GUU UGAUUGAG













4594




AUUGGGUG AGAA GUGCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGCACU GAU CACCCAAU













4628




GGCUGCAG AGAA GGCCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGGCCA GCC CUGCAGCC













4636




GGGUUUUG AGAA GCAGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCCUGCA GCC CAAAACCC













4866




AGGGUCAG AGAA GGGAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUCCCA GCU CUGACCCU













4871




GUAGAAGG AGAA GAGCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAGCUCU GAC CCUUCUAC













4905




CGCUGUCC AGAA GCUCCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGGAGCA GAU GGACAGCG













5233




CUGUGCAA AGAA GAAUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUAUUCU GUU UUGCACAG













5281




CUCCUCAG AGAA GCAUUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAAUGCA GUC CUGAGGAG













5319




UUUCCUCC AGAA GCCCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAGGGCU GAU GGAGGAAA













5358




GGUAUAGA AGAA GGGUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGACCCC GUC UCUAUACC













5392




UGGGUCCC AGAA GUGUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAACACA GUU GGGACCCA













5563




UGAGUCCC AGAA GGAGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUCUCCA GUU GGGACUCA













5622




AGUUUCAA AGAA GUUGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUCAACU GCU UUGAAACU













5738




UAGCAUCA AGAA GAGCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGCUCU GUU UGAUGCUA













5838




UAGCAUCA AGAA GAGCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGGUCU GUU UGAUGCUA













5933




CCCCAAGA AGAA GCAAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAUUGCU GCU UCUUGGGG













6022




CACAUAAG AGAA GAGGCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGCCUCU GUU CUUAUGUG













6120




UCCACAAA AGAA GCUGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCAGCG GCU UUUGUGGA













6163




GUGGAGAG AGAA GUCCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGGACA GUC CUCUCCAC













6270




AAAUUGCC AGAA GUCACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUGACA GCU GGCAAUUU













6412




AAGACAUG AGAA GCUAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUAGCU GUU CAUGUCUU













6511




UUUGAAGG AGAA GAGUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUACUCA GCU CCUUCAAA













6778




UCCACCCA AGAA GUUCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGAACA GUC UGGGUGGA













6826




ACUUCUUG AGAA GACAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUGUCA GUC CAAGAAGU













7245




AACAUAAA AGAA GUUGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCAACU GCU UUUAUGUU













7258




UGGAAGGA AGAA GAACAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUGUUCU GUC UCCUUCCA













7433




CCCAUACA AGAA GCUAAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUUAGCU GAU UGUAUGGG













7512




UUUUCAUG AGAA GGAAUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAUUCCU GUC CAUGAAAA













7606




GACAUUCA AGAA GAAAUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAUUUCA GCC UGAAUGUC













7618




AAUAUAUA AGAA GACAUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAUGUCU GCC UAUAUAUU













7633




AUACAAAG AGAA GAGAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUUCUCU GCU CUUUGUAU






















Table IV











Human KDR VEGF Receptor-Hammerhead Ribozyme and






Substrate Sequence













nt.








Position




HH Ribozyme Sequence




Substrate









  21




CACAGGGC CUGAUGA X GAA ACGGCCAG




CUGGCCGUC GCCCUGUG













  33




UCCACGCA CUGAUGA X GAA AGCCACAG




CUGUGGCUC UGCGUGGA













  56




AACCCACA CUGAUGA X GAA AGGCGGCC




GGCCGCCUC UGUGGGUU













  64




ACUAGGCA CUGAUGA X GAA ACCCACAG




CUGUGGGUU UGCCUAGU













  65




CACUAGGC CUGAUGA X GAA AACCCACA




UGUGGGUUU GCCUAGUG













  70




AGAAACAC CUGAUGA X GAA AGGCAAAC




GUUUGCCUA GUGUUUCU













  75




UCAAGAGA CUGAUGA X GAA ACACUAGG




CCUAGUGUU UCUCUUGA













  76




AUCAAGAG CUGAUGA X GAA AACACUAG




CUAGUGUUU CUCUUGAU













  77




GAUCAAGA CUGAUGA X GAA AAACACUA




UAGUGUUUC UCUUGAUC













  79




CAGAUCAA CUGAUGA X GAA AGAAACAC




GUGUUUCUC UUGAUCUG













  81




GGCAGAUC CUGAUGA X GAA AGAGAAAC




GUUUCUCUU GAUCUGCC













  85




CCUGGGGA CUGAUGA X GAA AUCAAGAG




CUCUUGAUC UGCCCAGG













  96




UGUAUGCU CUGAUGA X GAA AGCCUGGG




CCCAGGCUC AGCAUACA













 102




UCUUUUUG CUGAUGA X GAA AUGCUGAG




CUCAGCAUA CAAAAAGA













 114




AUUGUAAG CUGAUGA X GAA AUGUCUUU




AAAGACAUA CUUACAAU













 117




UUAAUUGU CUGAUGA X GAA AGUAUGUC




GACAUACUU ACAAUUAA













 118




CUUAAUUG CUGAUGA X GAA AAGUAUGU




ACAUACUUA CAAUUAAG













 123




UUAGCCUU CUGAUGA X GAA AUUGUAAG




CUUACAAUU AAGGCUAA













 124




AUUAGCCU CUGAUGA X GAA AAUUGUAA




UUACAAUUA AGGCUAAU













 130




AGUUGUAU CUGAUGA X GAA AGCCUUAA




UUAAGGCUA AUACAACU













 133




AAGAGUUG CUGAUGA X GAA AUUAGCCU




AGGCUAAUA CAACUCUU













 139




AAUUUGAA CUGAUGA X GAA AGUUGUAU




AUACAACUC UUCAAAUU













 141




GUAAUUUG CUGAUGA X GAA AGAGUUGU




ACAACUCUU CAAAUUAC













 142




AGUAAUUU CUGAUGA X GAA AAGAGUUG




CAACUCUUC AAAUUACU













 147




CUGCAAGU CUGAUGA X GAA AUUUGAAG




CUUCAAAUU ACUUGCAG













 148




CCUGCAAG CUGAUGA X GAA AAUUUGAA




UUCAAAUUA CUUGGAGG













 151




UCCCCUGC CUGAUGA X GAA AGUAAUUU




AAAUUACUU GCAGGGGA













 170




GCCAGUCC CUGAUGA X GAA AGUCCCUC




GAGGGACUU GGACUGGC













 180




UUGGGCCA CUGAUGA X GAA AGCCAGUC




GACUGGCUU UGGCCCAA













 181




AUUGGGCC CUGAUGA X GAA AAGCCAGU




ACUGGcUUU GGCCCAAU













 190




ACUCUGAU CUGAUGA X GAA AUUGGGCC




GGCCCAAUA AUCAAAGU













 193




GCCACUCU CUGAUGA X GAA AUUAUUGG




CCAAUAAUC AGAGUGGC













 243




UUACAGAA CUGAUGA X GAA AGGCCAUC




GAUGGCCUC UUCUGUAA













 245




UCUUACAG CUGAUGA X GAA ACAGGCCA




UGGCCUCUU CUGUAAGA













 246




GUCUUACA CUGAUGA X GAA AAGAGGCC




GGCCUCUUC UGUAAGAC













 250




GAGUGUCU CUGAUGA X GAA ACAGAAGA




UCUUCUGUA AGACACUC













 258




GGAAUUGU CUGAUGA X GAA AGUGUCUU




AAGACACUC ACAAUUCC













 264




ACUUUUGG CUGAUGA X GAA AUUGUGAG




CUCACAAUU CCAAAAGU













 265




CACUUUUG CUGAUGA X GAA AAUUGUGA




UCACAAUUC CAAAAGUG













 276




UCAUUUCC CUGAUGA X GAA AUCACUUU




AAAGUGAUC GGAAAUGA













 296




AGCACUUG CUGAUGA X GAA AGGCUCCA




UGGAGCCUA CAAGUGCU













 305




CCCGGUAG CUGAUGA X GAA AGCACUUG




CAAGUGCUU CUACCGGG













 306




UCCCGGUA CUGAUGA X GAA AAGCACUU




AAGUGCUUC UACCGGGA













 308




UUUCCCGG CUGAUGA X GAA AGAAGCAC




GUGCUUCUA CCGGGAAA













 323




CCGAGGCC CUGAUGA X GAA AGUCAGUU




AACUGACUU GGCCUCGG













 329




AAAUGACC CUGAUGA X GAA AGGCCAAG




CUUGGCCUC GGUCAUUU













 333




ACAUAAAU CUGAUGA X GAA ACCGAGGC




GCCUCGGUC AUUUAUGU













 336




UAGACAUA CUGAUGA X GAA AUGACCGA




UCGGUCAUU UAUGUCUA













 337




AUAGACAU CUGAUGA X GAA AAUGACCG




CGGUCAUUU AUGUCUAU













 338




CAUAGACA CUGAUGA X GAA AAAUGACC




GGUCAUUUA UGUCUAUG













 342




UGAACAUA CUGAUGA X GAA ACAUAAAU




AUUUAUGUC UAUGUUCA













 344




CUUGAACA CUGAUGA X CAA AGACAUAA




UUAUGUCUA UGUUCAAG













 348




UAAUCUUG CUGAUGA X GAA ACAUAGAC




GUCUAUGUU CAAGAUUA













 349




GUAAUCUU CUGAUGA X GAA AACAUAGA




UCUAUGUUC AAGAUUAC













 355




AGAUCUGU CUGAUGA X GAA AUCUUGAA




UUCAAGAUU ACAGAUCU













 356




GAGAUCUG CUGAUGA X GAA AAUCUUGA




UCAAGAUUA CAGAUCUC













 362




UAAAUGGA CUGAUGA X GAA AUCUGUAA




UUACAGAUC UCCAUUUA













 364




AAUAAAUG CUGAUGA X GAA AGAUCUGU




ACAGAUCUC CAUUUAUU













 368




AAGCAAUA CUGAUGA X GAA AUGGAGAU




AUCUCCAUU UAUUGCUU













 369




GAAGCAAU CUGAUGA X GAA AAUGGAGA




UCUCCAUUU AUUGCUUC













 370




AGAAGCAA CUGAUGA X GAA AAAUGGAG




CUCCAUUUA UUGCUUCU













 372




ACAGAAGC CUGAUGA X GAA AUAAAUGG




CCAUUUAUU GCUUCUGU













 376




ACUAACAG CUGAUGA X GAA AGCAAUAA




UUAUUGCUU CUGUUAGU













 377




CACUAACA CUGAUGA X GAA AAGCAAUA




UAUUGCUUC UGUUAGUG













 381




UGGUCACU CUGAUGA X GAA ACAGAAGC




GCUUCUGUU AGUGACCA













 382




UUGGUCAC CUGAUGA X GAA AACAGAAG




CUUCUGUUA GUGACCAA













 399




AUGUACAC CUGAUGA X GAA ACUCCAUG




CAUGGAGUC GUGUACAU













 404




CAGUAAUG CUGAUGA X GAA ACACGACU




AGUCGUGUA CAUUACUG













 408




UUCUCAGU CUGAUGA X GAA AUGUACAC




GUGUACAUU ACUGAGAA













 409




GUUCUCAG CUGAUGA X GAA AAUGUACA




UGUACAUUA CUGAGAAC













 438




AGACAUGG CUGAUGA X GAA AUCACCAC




GUGGUGAUU CCAUGUCU













 439




GAGACAUG CUGAUGA X GAA AAUCACCA




UGGUGAUUC CAUGUCUC













 445




GGACCCGA CUGAUGA X GAA ACAUGGAA




UUCCAUGUC UCGGGUCC













 447




AUGGACCC CUGAUGA X GAA AGACAUGG




CCAUGUCUC GGGUCCAU













 452




UUGAAAUG CUGAUGA X GAA ACCCGAGA




UCUCGGGUC CAUUUCAA













 456




AGAUUUGA CUGAUGA X GAA AUGGACCC




GGGUCCAUU UCAAAUCU













 457




GAGAUUUG CUGAUGA X GAA AAUGGACC




GGUCCAUUU CAAAUCUC













 458




UGAGAUUU CUGAUGA X GAA AAAUGGAC




GUCCAUUUC AAAUCUCA













 463




CACGUUGA CUGAUGA X GAA AUUUGAAA




UUUCAAAUC UCAACGUG













 465




GACACGUU CUGAUGA X GAA AGAUUUGA




UCAAAUCUC AACGUGUC













 473




CACAAAGU CUGAUGA X GAA ACACGUUG




CAACGUGUC ACUUUGUG













 477




CUUGCACA CUGAUGA X GAA AGUGACAC




GUGUCACUU UGUGCAAG













 478




UCUUGCAC CUGAUGA X GAA AAGUGACA




UGUCACUUU GUGCAAGA













 488




UUUCUGGG CUGAUGA X GAA AUCUUGCA




UGCAAGAUA CCCAGAAA













 503




CAGGAACA CUGAUGA X GAA AUCUCUUU




AAAGAGAUU UGUUCCUG













 504




UCAGGAAC CUGAUGA X GAA AAUCUCUU




AAGAGAUUU GUUCCUGA













 507




CCAUCAGG CUGAUGA X GAA ACAAAUCU




AGAUUUGUU CCUGAUGG













 508




ACCAUCAG CUGAUGA X GAA AACAAAUC




GAUUUGUUC CUGAUGGU













 517




AAUUCUGU CUGAUGA X GAA ACCAUCAG




CUGAUGGUA ACAGAAUU













 525




UCCCAGGA CUGAUGA X GAA AUUCUGUU




AACAGAAUU UCCUGGGA













 526




GUCCCAGG CUGAUGA X GAA AAUUCUGU




ACAGAAUUU CGGGGGAC













 527




UGUCCCAG CUGAUGA X GAA AAAUUCUG




CAGAAUUUC CUGGGACA













 548




GAAAAGUA CUGAUGA X GAA AGCCCUUC




GAAGGGCUU UACUAUUC













 549




GGAAUAGU CUGAUGA X GAA AAGCCCUU




AAGGGCUUU ACUAUUCC













 550




GCGAAUAG CUGAUGA X GAA AAAGCCCU




AGGGCUUUA CUAUUCCC













 553




GCUGGGAA CUGAUGA X GAA AGUAAAGC




GCUUUACUA UUCCCAGC













 555




UAGCUGGG CUGAUGA X GAA AUAGUAAA




UUUACUAUU CCCAGCUA













 556




GUAGCUGG CUGAUGA X GAA AAUAGUAA




UUACUAUUC CCAGCUAC













 563




UGAUCAUG CUGAUGA X GAA AGCUGGGA




UCCCAGCUA CAUGAUCA













 570




GCAUAGCU CUGAUGA X GAA AUCAUGUA




UACAUGAUC AGCUAUGC













 575




UGCCAGCA CUGAUGA X GAA AGCUGAUC




GAUCAGCUA UGCUGGCA













 588




UCACAGAA CUGAUGA X GAA ACCAUGCC




GCCAUGGUC UUCUGUGA













 590




CUUCACAG CUGAUGA X GAA AGACCAUG




CAUGGUCUU CUGUGAAG













 591




GCUUCACA CUGAUGA X GAA AAGACCAU




AUGGUCUUC UGUGAAGC













 606




UCAUCAUU CUGAUGA X GAA AUUUUUGC




GCAAAAAUU AAUGAUGA













 607




UUCAUCAU CUGAUGA X GAA AAUUUUUG




CAAAAAUUA AUGAUGAA













 619




AGACUGGU CUGAUGA X GAA ACUUUCAU




AUGAAAGUU ACCAGUCU













 620




UAGACUGG CUGAUGA X GAA AACUUUCA




UGAAAGUUA CCAGUCUA













 626




ACAUAAUA CUGAUGA X GAA ACUGGUAA




UUACCAGUC UAUUAUGU













 628




GUACAUAA CUGAUGA X GAA AGACUGGU




ACCAGUCUA UUAUGUAC













 630




AUGUACAU CUGAUGA X GAA AUAGACUG




CAGUCUAUU AUGUACAU













 631




UAUGUACA CUGAUGA X GAA AAUAGACU




AGUCUAUUA UGUACAUA













 635




CAACUAUG CUGAUGA X GAA ACAUAAUA




UAUUAUGUA CAUAGUUG













 639




ACGACAAC CUGAUGA X GAA AUGUACAU




AUGUACAUA GUUGUCGU













 642




ACAACGAC CUGAUGA X GAA ACUAUGUA




UACAUAGUU GUCGUUGU













 645




CCUACAAC CUGAUGA X GAA ACAACUAU




AUAGUUGUC GUUGUAGG













 648




UACCCUAC CUGAUGA X GAA ACGACAAC




GUUGUCGUU GUAGGGUA













 651




CUAUACCC CUGAUGA X GAA ACAACGAC




GUCGUUGUA GGGUAUAG













 656




AAAUCCUA CUGAUGA X GAA ACCCUACA




UGUAGGGUA UAGGAUUU













 658




AUAAAUCC CUGAUGA X GAA AUACCCUA




UAGGGUAUA GGAUUUAU













 663




ACAUCAUA CUGAUGA X GAA AUCCUAUA




UAUAGGAUU UAUGAUGU













 664




CACAUCAU CUGAUGA X GAA AAUCCUAU




AUAGGAUUU AUGAUGUG













 665




CCACAUCA CUGAUGA X GAA AAAUCCUA




UAGGAUUUA UGAUGUGG













 675




GGACUCAG CUGAUGA X GAA ACCACAUC




GAUGUGGUU CUGAGUCC













 676




CGGACUCA CUGAUGA X GAA AACCACAU




AUGUGGUUC UGAGUCCG













 682




AUGAGACG CUGAUGA X GAA ACUCAGAA




UUCUGAGUC CGUCUCAU













 686




UUCCAUGA CUGAUGA X GAA ACGGACUC




GAGUCCGUC UCAUGGAA













 688




AAUUCCAU CUGAUGA X GAA AGACGGAC




GUCCGUCUC AUGGAAUU













 696




GAUAGUUC CUGAUGA X GAA AUUCCAUG




CAUGGAAUU GAACUAUC













 702




CCAACAGA CUGAUGA X GAA AGUUCAAU




AUUGAACUA UCUGUUGG













 704




CUCCAACA CUGAUGA X GAA AUAGUUCA




UGAACUAUC UGUUGGAG













 708




UUUUCUCC CUGAUGA X GAA ACAGAUAG




CUAUCUGUU GGAGAAAA













 720




UUUAAGAC CUGAUGA X GAA AGCUUUUC




GAAAAGCUU GUCUUAAA













 723




CAAUUUAA CUGAUGA X GAA ACAAGCUU




AAGCUUGUC UUAAAUUG













 725




UACAAUUU CUGAUGA X GAA AGACAAGC




GCUUGUCUU AAAUUGUA













 726




GUACAAUU CUGAUGA X GAA AAGACAAG




CUUGUCUUA AAUUGUAC













 730




UGCUGUAC CUGAUGA X GAA AUUUAAGA




UCUUAAAUU GUACAGCA













 733




UCUUGCUG CUGAUGA X GAA ACAAUUUA




UAAAUUGUA CAGCAAGA













 750




CCCACAUU CUGAUGA X GAA AGUUCAGU




ACUGAACUA AAUGUGGG













 762




UUGAAGUC CUGAUGA X GAA AUCCCCAC




GUGGGGAUU GACUUCAA













 767




CCCAGUUG CUGAUGA X GAA AGUGAAUC




GAUUGACUU CAACUGGG













 768




UCCCAGUU CUGAUGA X GAA AAGUCAAU




AUUGACUUC AACUGGGA













 779




AAGAAGGG CUGAUGA X GAA AUUCCCAG




CUGGGAAUA CCCUUCUU













 784




CUUCGGAG CUGAUGA X GAA AGGGUAUU




AAUACCCUU CUUCGGAG













 785




GCUUCGAA CUGAUGA X GAA AAGGGUAU




AUACCCUUC UUCGAAGC













 787




AUGCUUCG CUGAUGA X GAA AGAAGGGU




ACCCUUCUU CGAAGCAU













 788




GAUGCUUC CUGAUGA X GAA AAGAAGGG




CCCUUCUUC GAAGCAUC













 796




CUUAUGCU CUGAUGA X GAA AUGCUUCG




CGAAGCAUC AGCAUAAG













 802




AAGUUUCU CUGAUGA X GAA AUGCUGAU




AUCAGCAUA AGAAACUU













 810




CGGUUUAC CUGAUGA X GAA AGUUUCUU




AAGAAACUU GUAAACCG













 813




UCUCGGUU CUGAUGA X GAA ACAAGUUU




AAACUUGUA AACCGAGA













 825




UGGGUUUU CUGAUGA X GAA AGGUCUCG




GGAGACCUA AAAACCCA













 836




CACUCCCA CUGAUGA X GAA ACUGGGUU




AACCCAGUC UGGGAGUG













 857




UGCUCAAA CUGAUGA X GAA AUUUCUUC




GAAGAAAUU UUUGAGCA













 858




GUGCUCAA CUGAUGA X GAA AAUUUCUU




AAGAAAUUU UUGAGCAC













 859




GGUGCUCA CUGAUGA X GAA AAAUUUCU




AGAAAUUUU UGAGCACC













 860




AGGUGCUC CUGAUGA X GAA AAAAUUUC




GAAAUUUUU GAGCACCU













 869




CUAUAGUU CUGAUGA X GAA AGGUGCUC




GAGCACCUU AACUAUAG













 870




UCUAUAGU CUGAUGA X GAA AAGGUGCU




AGCACCUUA ACUAUAGA













 874




ACCAUCUA CUGAUGA X GAA AGUUAAGG




CCUUAACUA UAGAUGGU













 876




ACACCAUC CUGAUGA X GAA AUAGUUAA




UUAACUAUA GAUGGUGU













 885




CUCCGGGU CUGAUGA X GAA ACACCAUC




GAUGGUGUA ACCCGGAG













 905




AGGUGUAC CUGAUGA X GAA AUCCUUGG




CCAAGGAUU GUACACCU













 908




CACAGGUG CUGAUGA X GAA ACAAUCCU




AGGAUUGUA CACCUGUG













 923




GCCCACUG CUGAUGA X GAA AUGCUGCA




UGCAGCAUC CAGUGGGC













 956




CCCUGACA CUGAUGA X GAA AUGUGCUG




CAGCACAUU UGUCAGGG













 957




ACCCUGAC CUGAUGA X GAA AAUGUGCU




AGCACAUUU GUCAGGGU













 960




UGGACCCU CUGAUGA X GAA ACAAAUGU




ACAUUUGUC AGGGUCCA













 966




UUUUCAUG CUGAUGA X GAA ACCCUGAC




GUCAGGGUC CAUGAAAA













 979




AGCAACAA CUGAUGA X GAA AGGUUUUU




AAAAACCUU UUGUUGCU













 980




AAGCAACA CUGAUGA X GAA AAGGUUUU




AAAACGUUU UGUUGCCU













 981




AAAGCAAC CUGAUGA X GAA AAAGGUUU




AAACCUUUU GUUGCUUU













 984




CCAAAAGC CUGAUGA X GAA ACAAAAGG




CCUUUUGUU GCUUUUGG













 988




ACUUCCAA CUGAUGA X GAA AGCAACAA




UUGUUGCUU UUGGAAGU













 989




CACUUCCA CUGAUGA X GAA AAGCAACA




UGUUGCUUU UGGAAGUG













 990




CCACUUCC CUGAUGA X GAA AAAGCAAC




GUUGCUUUU GGAAGUGG













1007




CCACCAGA CUGAUGA X GAA AUUCCAUG




CAUGGAAUC UGUGGUGG













1009




UUCCACCA CUGAUGA X GAA AGAUUCCA




UGGAAUCUC UGGUGGAA













1038




GGGAUUCU CUGAUGA X GAA ACACGCUC




GAGCGUGUC AGAAUCCC













1044




UUCGCAGG CUGAUGA X GAA AUUCUGAC




GUCAGAAUC CCUGCGAA













1055




AACCAAGG CUGAUGA X GAA ACUUCGCA




UGCGAAGUA CCUUGGUU













1059




GGGUAACC CUGAUGA X GAA AGGUACUU




AAGUACCUU GGUUACCC













1063




GGGUGGGU CUGAUGA X GAA ACCAAGGU




ACCUUGGUU ACCCACCC













1064




GGGGUGGG CUGAUGA X GAA AACCAAGG




CCUUGGUUA CCCACCCC













1080




UACCAUUU CUGAUGA X GAA AUUUCUGG




CCAGAAAUA AAAUGGUA













1088




CAUUUUUA CUGAUGA X GAA ACCAUUUU




AAAAUGGUA UAAAAAUG













1090




UCCAUUUU CUGAUGA X GAA AUACCAUU




AAUGGUAUA AAAAUGGA













1101




UCAAGGGG CUGAUGA X GAA AUUCCAUU




AAUGGAAUA CCCCUUGA













1107




UUGGACUC CUGAUGA X GAA AGGGGUAU




AUACCCCUU GAGUCCAA













1112




UGUGAUUG CUGAUGA X GAA ACUCAAGG




CCUUGAGUC CAAUCACA













1117




AAUUGUGU CUGAUGA X GAA AUUGGACU




AGUCCAAUC ACACAAUU













1125




CCCGCUUU CUGAUGA X GAA AUUGUGUG




CACACAAUU AAAGCGGG













1126




CCCGGCUU CUGAUGA X GAA AAUUGUGU




ACACAAUUA AAGCGGGG













1140




AUCGUCAG CUGAUGA X GAA ACAUGCCC




GGGCAUGUA CUGACGAU













1149




ACUUCCAU CUGAUGA X GAA AUCGUCAG




CUGACGAUU AUGGAAGU













1150




CACUUCCA CUGAUGA X GAA AAUCGUCA




UGACGAUUA UGGAAGUG













1180




GACAGUGU CUGAUGA X GAA AUUUCCUG




CAGGAAAUU ACACUGUC













1181




UGACAGUG CUGAUGA X GAA AAUUUCCU




AGGAAAUUA CACUGUCA













1188




GUAAGGAU CUGAUGA X GAA ACAGUGUA




UACACUGUC AUCCUUAC













1191




UUGGUAAG CUGAUGA X GAA AUGACAGU




ACUGUCAUC CUUACCAA













1194




GGAUUGGU CUGAUGA X GAA AGGAUGAC




GUCAUCCUU ACCAAUCC













1195




GGGAUUGG CUGAUGA X GAA AAGGAUGA




UCAUCCUUA CCAAUCCC













1201




UGAAAUGG CUGAUGA X GAA AUUGGUAA




UUACCAAUC CCAUUUCA













1206




UCCUUUGA CUGAUGA X GAA AUGGGAUU




AAUCCCAUU UCAAAGGA













1207




CUCGUUUG CUGAUGA X GAA AAUGGGAU




AUCCCAUUU CAAAGGAG













1208




UCUCCUUU CUGAUGA X GAA AAAUGGGA




UCCCAUUUC AAAGGAGA













1233




ACCAGAGA CUGAUGA X GAA ACCACAUG




CAUGUGGUC UCUCUGGU













1235




CAACCAGA CUGAUGA X GAA AGACCACA




UGUGGUCUC UCUGGUUG













1237




CACAACCA CUGAUGA X GAA AGAGACCA




UGGUCUCUC UGGUUGUG













1242




ACAUACAC CUGAUGA X GAA ACCAGAGA




UCUCUGGUU GUGUAUGU













1247




GUGGGACA CUGAUGA X GAA ACACAACC




GGUUGUGUA UGUCCCAC













1251




UGGGGUGG CUGAUGA X GAA ACAUACAC




GUGUAUGUC CCACCCCA













1263




UUCUCACC CUGAUGA X GAA AUCUGGGG




CCCCAGAUU GGUGACAA













1274




AGAUUAGA CUGAUGA X GAA AUUUCUCA




UGAGAAAUC UCUAAUCU













1276




AGAGAUUA CUGAUGA X GAA AGAUUUCU




AGAAAUCUC UAAUCUCU













1278




GGAGAGAU CUGAUGA X GAA AGAGAUUU




AAAUCUCUA AUCUCUCC













1281




ACAGGAGA CUGAUGA X GAA AUUAGAGA




UCUCUAAUC UCUCCUGU













1283




CCACAGGA CUGAUGA X GAA AGAUUAGA




UCUAAUCUC UCCUGUGG













1285




AUCCACAG CUGAUGA X GAA AGAGAUUA




UAAUCUCUC CUGUGGAU













1294




CUGGUAGG CUGAUGA X GAA AUCCACAG




CUGUGGAUU CCUACCAG













1295




ACUGGUAG CUGAUGA X GAA AAUCCACA




UGUGGAUUC CUACCAGU













1298




CGUACUGG CUGAUGA X GAA AGGAAUCC




GGAUUCCUA CCAGUACG













1304




UGGUGCCG CUGAUGA X GAA ACUGGUAG




CUACCAGUA CGCCACCA













1315




CAGCGUUU CUGAUGA X GAA AGUGGUGC




GCACCACUC AAACGCUG













1330




AUAGACCG CUGAUGA X GAA ACAUGUCA




UGACAUGUA CGGUCUAU













1335




AUGGCAUA CUGAUGA X GAA ACCGUACA




UGUACGGUC UAUGCCAU













1337




GAAUGGCA CUGAUGA X GAA AGACCGUA




UACGGUCUA UGCCAUUC













1344




GGGGGAGG CUGAUGA X GAA AUGGCAUA




UAUGCCAUU CCUCCCCC













1345




CGGGGGAG CUGAUGA X GAA AAUGGCAU




AUGCCAUUC CUCCCCCG













1348




AUGCGGGG CUGAUGA X GAA AGGAAUGG




CCAUUCCUC CCCCGCAU













1357




GUGGAUGU CUGAUGA X GAA AUGCGGGG




CCCCGCAUC ACAUCCAC













1362




UACCAGUG CUGAUGA X GAA AUGUGAUG




CAUCACAUC CACUGGUA













1370




ACUGCCAA CUGAUGA X GAA ACCAGUGG




CCACUGGUA UUGGCAGU













1372




CAACUGCC CUGAUGA X GAA AUACCAGU




ACUGGUAUU GCCAGUUG













1379




CUUCCUCC CUGAUGA X GAA ACUGCCAA




UUGGCAGUU GGAGGAAG













1416




GUCACUGA CUGAUGA X GAA ACAGCUUG




CAAGCUGUC UCAGUGAC













1418




UUGUCACU CUGAUGA X GAA AGACAGCU




AGCUGUCUC AGUGACAA













1433




CACAAGGG CUGAUGA X GAA AUGGGUUU




AAACCCAUA CCCUUGUG













1438




UUCUUCAC CUGAUGA X GAA AGGGUAUG




CAUACCCUU GUGAACAA













1466




CUCCCUGG CUGAUGA X GAA AGUCCUCC




GGAGGACUU CCAGGGAG













1467




CCUCCCUG CUGAUGA X GAA AAGUCCUC




GAGGACUUC CAGGGAGG













1480




UUCAAUUU CUGAUGA X GAA AUUUCCUC




GAGGAAAUA AAAUUGAA













1485




UUAACUUC CUGAUGA X GAA AUUUUAUU




AAUAAAAUU GAAGUUAA













1491




UUUUUAUU CUGAUGA X GAA ACUUCAAU




AUUGAAGUU AAUAAAAA













1492




AUUUUUAU CUGAUGA X GAA AAGUUCAA




UUGAAGUUA AUAAAAAU













1495




UGGAUUUU CUGAUGA X GAA AUUAACUU




AAGUUAAUA AAAAUCAA













1501




AGCAAAUU CUGAUGA X GAA AUUUUUAU




AUAAAAAUC AAUUUGCU













1505




UUAGAGCA CUGAUGA X GAA AUUGAUUU




AAAUCAAUU UGCUCUAA













1506




AUUAGAGC CUGAUGA X GAA AAUUGAUU




AAUCAAUUU GCUCUAAU













1510




UUCAAUUA CUGAUGA X GAA AGCAAAUU




AAUUUGCUC UAAUAGAA













1512




CCUUCAAU CUGAUGA X GAA AGAGCAAA




UUUGCUCUA AUUGAAGG













1515




UUUCCUUC CUGAUGA X GAA AUUAGAGC




GCUCUAAUU GAAGCAAA













1536




AGGGUACU CUGAUGA X GAA ACAGUUUU




AAAACUGUA AGUACCCU













1540




AACAAGGG CUGAUGA X GAA ACUUACAG




CUGUAAGUA CCCUUGUU













1545




UGGAUAAC CUGAUGA X GAA AGGGUACU




AGUACCCUU CUUAUCCA













1548




GCUUGGAU CUGAUGA X GAA ACAAGGGU




ACCCUUGUU AUCCAAGC













1549




CGCUUGGA CUGAUGA X GAA AACAAGGG




CCCUUGUUA UCCAAGCG













1551




GCCGCUUG CUGAUGA X GAA AUAACAAG




CUUGUUAUC CAAGCGGC













1568




ACAAAGCU CUGAUGA X GAA ACACAUUU




AAAUGUGUC AGCUUUGU













1573




UUUGUACA CUGAUGA X GAA AGCUGACA




UGUCAGUUU UGUACAAA













1574




AUUUGUAC CUGAUGA X GAA AAGCUGAC




GUCAGCUUU GUACAAAU













1577




CACAUUUG CUGAUGA X GAA ACAAAGCU




AGCUUUGUA CAAAUGUG













1593




ACUUUGUU CUGAUGA X GAA ACCGCUUC




GAAGCGGUC AACAAAGU













1602




CCUCUCCC CUGAUGA X GAA ACUUUGUU




AACAAAGUC GGGAGAGG













1623




UGGAAGGA CUGAUGA X GAA AUCACCCU




AGGGUGAUC UCCUUCCA













1625




CGUGGAAG CUGAUGA X GAA AGAUCACC




GGUGAUCUC CUUCCACG













1628




UCACGUGG CUGAUGA X GAA AGGAGAUC




GAUCUCCUU CCACGUGA













1629




GUCACGUG CUGAUGA X GAA AAGGAGAU




AUCUCCUUC CACGUGAC













1645




AAUUUCAG CUGAUGA X GAA ACCCCUGG




CCAGGGGUC CUGAAAUU













1653




UGCAAAGU CUGAUGA X GAA AUUUCAGG




CCUGAAAUU ACUUUGCA













1654




UUGCAAAG CUGAUGA X GAA AAUUUCAG




CUGAAAUUA CUUUGCAA













1657




AGGUUGCA CUGAUGA X GAA AGUAAUUU




AAAUUACUU UGCAACCU













1658




CAGGUUGC CUGAUGA X GAA AAGUAAUU




AAUUACUUU GCAACCUG













1697




ACCACAAA CUGAUGA X GAA ACACGCUC




GAGCGUGUC UUUGUGGU













1699




GCACCACA CUGAUGA X GAA AGACACGC




GCGUGUCUU UGUGGUGC













1700




UGCACCAC CUGAUGA X GAA AAGACACG




CGUGUCUUU GUGGUGCA













1721




CAAACGUA CUGAUGA X GAA AUCUGUCU




AGACAGAUC UACGUUUG













1723




CUCAAACG CUGAUGA X GAA AGAUCUGU




ACAGAUCUA CGUUUGAG













1727




GGUUCUCA CUGAUGA X GAA ACGUAGAU




AUCUACGUU UGAGAACC













1728




AGGUUCUC CUGAUGA X GAA AACGUAGA




UCUACGUUU GAGAACCU













1737




UACCAUGU CUGAUGA X GAA AGGUUCUC




GAAAACCUC ACAUGGUA













1745




CAAGCUUG CUGAUGA X GAA ACCAUGUG




CACAUGGUA CAAGCUUG













1752




UGUGGGCC CUGAUGA X GAA AGCUUGUA




UACAAGCUU GGCCCACA













1765




GAUUGGCA CUGAUGA X GAA AGGCUGUG




CACAGCCUC UGCCAAUC













1773




CCCACAUG CUGAUGA X GAA AUUGGCAG




CUGCCAAUC CAUGUGGG













1787




GUGUGGGC CUGAUGA X GAA ACUCUCCC




GGGAGAGUU GCCCACAC













1800




UUCUUGCA CUGAUGA X GAA ACAGGUGU




ACACCUGUU UGCAAGAA













1801




GUUCUUGC CUGAUGA X GAA AACAGGUG




CACCUGUUU GCAAGAAC













1811




GAGUAUCC CUGAUGA X GAA AGUUCUUG




CAAGAACUU GGAUACUC













1816




CCAAAGAG CUGAUGA X GAA AUCCAAGU




ACUUGGAUA CUCUUUGG













1819




UUUCCAAA CUGAUGA X GAA AGUAUCCA




UGGAUACUC UUUGGAAA













1821




AAUUUCCA CUGAUGA X GAA AGAGUAUC




GAUACUCUU UGGAAAUU













1822




CAAUUUCC CUGAUGA X GAA AAGAGUAU




AUACUCUUU GGAAAUUG













1829




UGGCAUUC CUGAUGA X GAA AUUUCCAA




UUGGAAAUU GAAUGCCA













1844




UAUUAGAG CUGAUGA X GAA ACAUGGUG




CACCAUGUU CUCUAAUA













1845




CUAUUAGA CUGAUGA X GAA AACAUGGU




ACCAUGUUC UCUAAUAG













1847




UGCUAUUA CUGAUGA X GAA AGAACAUG




CAUUUUCUC UAAUAGCA













1849




UGUGCCAU CUGAUGA X GAA AGAGAACA




UGUUCUCUA AUAGCACA













1852




AUUUGUGC CUGAUGA X GAA AUUAGAGA




UCUCUAAUA GCACAAAU













1866




AUGAUCAA CUGAUGA X GAA AUGUCAUU




AAUGAGAUU UUGAUCAU













1867




CAUGAUCA CUGAUGA X GAA AAUGUCAU




AUGAGAUUU UGAUCAUG













1868




CCAUGAUC CUGAUGA X GAA AAAUGUCA




UGACAUUUU GAUCAUGG













1872




AGCUCCAU CUGAUGA X GAA AUCAAAAU




AUUGAUCUU AUGGAGCU













1881




GCAUUCUU CUGAUGA X GAA AGCUCCAU




AUGGAGCUU AAGAAUGC













1882




UGCAUUCU CUGAUGA X GAA AAGCUCCA




UGGAGCUUA AGAAUGCA













1892




CCUGCAAG CUGAUGA X GAA AUGCAUUC




GAAUGCAUC CUUGCAGG













1895




GGUCCUGC CUGAUGA X GAA AGGAUGCA




UGCAUCCUU GCAGGACC













1913




GGCAGACA CUGAUGA X GAA AGUCUCCU




AGGAGACUA UGUCUGCC













1917




GCAAGGCA CGGAUGA X GAA ACAUAGUC




GACUAUGUC UGCCUUGC













1923




UCUUGAGC CUGAUGA X GAA AGGCAGAC




GUCUGCCUU GCUCAAGA













1927




CCUGUCUU CUGAUGA X GAA AGCAAGGC




GCCUUGCUC AAGACAGG













1954




GACCACGC CUGAUGA X GAA AUGUCUUU




AAAGACAUU GCGUGGUC













1962




AGCUGCCU CUGAUGA X GAA ACCACGCA




UGCGUGGUC AGGCAGCU













1971




AGGACUGU CUGAUGA X GAA AGCUGCCU




AGGCAGCUC ACAGUCUU













1977




CGCUCUAG CUGAUGA X GAA ACUGUGAG




CUCACAGUC CUAGAGCG













1980




ACACGCUC CUGAUGA X GAA AGGACUGU




ACAGUCCUA GAGCGUGU













2001




UUUCCUGU CUGAUGA X GAA AUCGUGGG




CCCACGAUC ACAGGAAA













2020




UGUCGUCU CUGAUGA X GAA AUUCUCCA




UGGAGAAUC AGACGACA













2032




UUCCCCAA CUGAUGA X GAA ACUUGUCG




CGACAAGUA UUGGGGAA













2034




CUUUCCCC CUGAUGA X GAA AUACUUGU




ACAAGUAUU GGGGAAAG













2046




GAGACUUC CUGAUGA X GAA AUGCUUUC




GAAAGCAUC GAAGUCUC













2052




GUGCAUGA CUGAUGA X GAA ACUUCGAU




AUCGAAGUC UCAUGCAC













2054




CCGUGCAU CUGAUGA X GAA AGACUUCG




CGAAGUCUC AUGCACGG













2066




GAUUCCCA CUGAUGA X GAA AUGCCGUG




CACGCCAUC UGGGAAUC













2074




UGGAGGGG CUGAUGA X GAA AUUCCCAG




CUGGGAAUC CCCCUCCA













2080




GAUCUGUG CUGAUGA X GAA AGGGGGAU




AUCCCCCUC CACAGAUC













2088




AACCACAU CUGAUGA X GAA AUCUGUGG




CCACAGAUC AUGUGGUU













2096




UAUCUUUA CUGAUGA X GAA ACCACAUG




CAUGUGGUU UAAAGAUA













2097




UUAUCUUU CUGAUGA X GAA AACCACAU




AUGUGGUUU AAAGAUAA













2098




AUUAUCUU CUGAUGA X GAA AAACCACA




UGUGGUUUA AAGAUAAU













2104




GGUCUCAU CUGAUGA X GAA AUCUUUAA




UUAAAGAUA AUGAGACC













2115




UCUUCUAC CUGAUGA X GAA AGGGUCUC




GAGACCCUU GUAGAAGA













2118




GAGUCUUC CUGAUGA X GAA ACAAGGGU




ACCCUUGUA GAAGACUC













2126




CAAUGCCU CUGAUGA X GAA AGUCUUCU




AGAAGACUC AGGCAUUG













2133




UUCAAUAC CUGAUGA X GAA AUGCCUGA




UCAGGCAUU GUAUUGAA













2136




UCCUUCAA CUGAUGA X GAA ACAAUGCC




GCCAUUGUA UUGAAGGA













2138




CAUCCUUC CUGAUGA X GAA AUACAAUG




CAUUGUAUU GAAGGAUG













2160




CGGAUAGU CUGAUGA X GAA AGGUUCCG




CGGAACCUC ACUAUCCG













2164




UCUGCGGA CUGAUGA X GAA AGUGAGGU




ACCUCACUA UCCGCAGA













2166




ACUCUGCG CUGAUGA X GAA AUAGUGAG




CUCACUAUC CGCAGAGU













2196




CAGGUGUA CUGAUGA X GAA AGGCCUUC




GAAGGCCUC UACACCUG













2198




GGCAGGUG CUGAUGA X GAA AGAGGCCU




AGGCCUCUA CACCUGCC













2220




CAGCCAAG CUGAUGA X GAA ACACUGGA




UGCAGUGUU CUUGGCUG













2221




ACAGCCAA CUGAUGA X GAA AACACUGC




GCAGUGUUC UUGGCUGU













2223




GCACAGCC CUGAUGA X GAA AGAACACU




AGUGUUCUU GGCUGUGC













2246




UUAUGAAA CUGAUGA X GAA AUGCCUCC




GGAGGCAUU UUUCAUAA













2247




AUUAUGAA CUGAUGA X GAA AAUGCCUC




GAGGCAUUU UUCAUAAU













2248




UAUUAUGA CUGAUGA X GAA AAAUGCCU




AGGCAUUUU UCAUAAUA













2249




CUAUUAUG CUGAUGA X GAA AAAAUGCC




GGCAUUUUU CAUAAUAG













2250




UCUAUUAU CUGAUGA X GAA AAAAAUGC




GGAUUUUUC AUAAUAGA













2253




CCUUCUAU CUGAUGA X GAA AUGAAAAA




UUUUUCAUA AUAGAAGG













2256




GCACCUUC CUGAUGA X GAA AUUAUGAA




UUCAUAAUA GAAGGUGC













2282




UGAUUUCC CUGAUGA X GAA AGUUCGUC




GACGAACUU GGAAAUCA













2289




AGAAUAAU CUGAUGA X GAA AUUUCCAA




UUGGAAAUC AUUAUUCU













2292




ACUAGAAU CUGAUGA X GAA AUGAUUUC




GAAAUCAUU AUUCUAGU













2293




UACUAGAA CUGAUGA X GAA AAUGAUUU




AAAUCAUUA UUCUAGUA













2295




CCUACUAG CUGAUGA X GAA AUAAUGAU




AUCAUUAUU CUAGUAGG













2296




GCCUACUA CUGAUGA X GAA AAUAAUGA




UCAUUAUUC UAGUAGGC













2298




GUGCCUAC GUGAUGA X GAA AGAAUAAU




AUUAUUCUA GUAGGGAC













2301




GUCGUGCC CUGAUGA X GAA ACUAGAAU




AUUCUAGUA GGCACGAC













2316




AACAUGGC CUGAUGA X GAA AUCACCGU




ACGGUGAUU GCCAUGUU













2324




GCCAGAAG CUGAUGA X GAA ACAUGGCA




UGCCAUGUU CUUCUGGC













2325




AGCCAGAA CUGAUGA X GAA AACAUGGC




GCCAUGUUC UUCUGGCU













2327




GUAGCCAG CUGAUGA X GAA AGAACAUG




CAUGUUCUU CUGGCUAC













2328




AGUAGCCA GUGAUGA X GAA AAGAACAU




AUGUUCUUC UGGCUACU













2334




ACAAGAAG GUGAUGA X GAA AGCCAGAA




UUCUGGCUA CUUCUGGU













2337




AUGACAAG CUGAUGA X GAA AGUAGCCA




UGGCUACUU CUUGUCAU













2338




GAUGACAA CUGAUGA X GAA AAGUAGCC




GGCUACUUC UUGUCAUC













2340




AUGAUGAC CUGAUGA X GAA AGAAGUAG




CUACUUCUU GUCAUCAU













2343




AGGAUGAU CUGAUGA X GAA ACAAGAAG




CUUCUUGUC AUCAUCCU













2346




CCUAGGAU CUGAUGA X GAA AUGACAAG




CUUGUCAUC AUCCUAGG













2349




GUCCCUAG CUGAUGA X GAA AUGAUGAC




GUCAUCAUC CUAGGGAC













2352




ACGGUCCC CUGAUGA X GAA AGGAUGAU




AUCAUCCUA GGGACCGU













2361




GCCCGCUU CUGAUGA X GAA ACGGUCCC




GGGACCGUU AAGCGGGC













2362




GGCCCGCU CUGAUGA X GAA AACGGUCC




GGACCGUUA AGCGGGCC













2396




UGGACAAG CUGAUGA X GAA AGCCUGUC




GACAGGCUA CUUGUCCA













2399




CGAUGGAC CUGAUGA X GAA AGUAGCCU




AGGCUACUU GUCCAUCG













2402




UGACGAUG CUGAUGA X GAA ACAAGUAG




CUACUUGUC CAUCGUCA













2406




UCCAUGAC CUGAUGA X GAA AUGGACAA




UUGUCCAUC GUCAUGGA













2409




GGAUCCAU CUGAUGA X GAA ACGAUGGA




UCCAUCGUC AUGGAUCC













2416




UUCAUCUG CUGAUGA X GAA AUCCAUGA




UCAUGGAUC CAGAUGAA













2427




UCCAAUGG CUGAUGA X GAA AGUUCAUC




GAUGAACUC CCAUUGGA













2432




GUUCAUCC CUGAUGA X GAA AUGGGAGU




ACUCCCAUU GGAUGAAC













2443




UCGUUCAC CUGAUGA X GAA AUGUUCAU




AUGAACAUU GUGAACGA













2458




GGCAUCAU CUGAUGA X GAA AGGCAGUC




GACUGCCUU AUGAUGCC













2459




UGGCAUCA CUGAUGA X GAA AAGGCAGU




ACUGCCUUA UGAUGCCA













2480




CUCUGGGG CUGAUGA X GAA AUUCCCAU




AUGGGAAUU CCCCAGAG













2481




UCUCUGGG CUGAUGA X GAA AAUUCCCA




UGGGAAUUC CCCAGAGA













2502




GGCUUACC CUGAUGA X GAA AGGUUCAG




CUGAACCUA GGUAAGCC













2506




AAGAGGCU CUGAUGA X GAA ACCUAGGU




ACCUAGGUA AGCCUCUU













2512




ACGGCCAA CUGAUGA X GAA AGGCUUAC




GUAAGCCUC UUGGCCGU













2514




CCACGGCC CUGAUGA X GAA AGAGGCUU




AAGCCUCUU GGCCGUGG













2528




CUUGGCCA CUGAUGA X GAA AGGCACCA




UGGUGCCUU UGGCCAAG













2529




UCUUGGCC CUGAUGA X GAA AAGGCACC




GGUGCCUUU GGCCAAGA













2541




UCUGCUUC CUGAUGA X GAA AUCUCUUG




CAAGAGAUU GAAGCAGA













2555




CAAUUCCA CUGAUGA X GAA AGGCAUCU




AGAUGCCUU UGGAAUUG













2556




UCAAUUCC CUGAUGA X GAA AAGGCAUC




GAUGCCUUU GGAAUUGA













2562




GUCUUGUC CUGAUGA X GAA AUUCGAAA




UUUGGAAUU GACAAGAC













2578




UGUCCUGC CUGAUGA X GAA AGUUGCUG




CAGCAACUU GCAGGACA













2589




UUGACUGC CUGAUGA X GAA ACUGUCCU




AGGACAGUA GCAGUCAA













2595




AACAUUUU CUGAUGA X GAA ACUGCUAC




GUAGCAGUC AAAAUGUU













2603




CUUCUUUC CUGAUGA X GAA ACAUUUUG




CAAAAUGUU GAAAGAAG













2632




GAGAGCUC CUGAUGA X GAA AUGCUCAC




GUGAGCAUC GAGCUCUC













2638




AGACAUGA CUGAUGA X GAA AGCUCGAU




AUCGAGCUC UCAUGUCU













2640




UCAGACAU CUGAUGA X GAA AGAGCUCG




CGAGCUCUC AUGUCUGA













2645




UGAGUUCA CUGAUGA X GAA ACAUGAGA




UCUCAUGUC UGAACUCA













2652




AGGAUCUU CUGAUGA X GAA AGUUCAGA




UCUGAACUC AAGAUCCU













2658




UGAAUGAG CUGAUGA X GAA AUCUUGAG




CUCAAGAUC CUCAUUCA













2661




AUAUGAAU CUGAUGA X GAA AGGAUCUU




AAGAUCCUC AUUCAUAU













2664




CCAAGAUG CUGAUGA X GAA AUGAGGAU




AUCCUCAUU CAUAUUGG













2665




ACCAAUAU CUGAUGA X GAA AAUGAGGA




UCCUCAUUC AUAUUGGU













2668




GUGACCAA CUGAUGA X GAA AUGAAUGA




UCAUUCAUA UUGGUCAC













2670




UGGGGACC CUGAUGA X GAA AUAUGAAU




AUUCAUAUU GGUCACCA













2674




GAGAUGGU CUGAUGA X GAA ACCAAUAU




AUAUUGGUC ACCAUCUC













2680




CACAUUGA CUGAUGA X GAA AUGGUGAC




GUCACCAUC UCAAUGUG













2682




ACCACAUU CUGAUGA X GAA AGAUGGUG




CACCAUCUC AAUGUGGU













2691




AGAAGGUU CUGAUGA X GAA ACCACAUU




AAUGUGGUC AACCUUCU













2697




GCACCUAG CUGAUGA X GAA AGGUUGAC




GUCAACCUU CUAGGUGC













2698




GGCACCUA CUGAUGA X GAA AAGGUUGA




UCAACCUUC UAGGUGCC













2700




CAGGCACC CUGAUGA X GAA AGAAGGUU




AACCUUCUA GGUGCCUG













2710




UGGCUUGG CUGAUGA X GAA ACAGGCAC




GUGCCUGUA CCAAGCCA













2730




AUCACCAU CUGAUGA X GAA AGUGGCCC




GGGCCACUC AUGUUGAU













2739




AAUUCCAC CUGAUGA X GAA AUCACCAU




AUGGUGAUU GUGGAAUU













2747




AUUUGCAG CUGAUGA X GAA AUUCCACA




UGUGGAAUU CUGCAAAU













2748




AAUUUGCA CUGAUGA X GAA AAUUCCAC




GUGGAAUUC UGCAAAUU













2756




GGUUUCCA CUGAUGA X GAA AUUUGCAG




CUGCAAAUU UGGAAACC













2757




AGGUUUCC CUGAUGA X GAA AAUUUGCA




UGCAAAUUU GGAAACCU













2768




GGUAAGUG CUGAUGA X GAA ACAGGUUU




AAACCUGUC CACUUACC













2773




CCUCAGGU CUGAUGA X GAA AGUGGACA




UGUCCACUU ACCUGAGG













2774




UCCUCAGG CUGAUGA X GAA AAGUGGAC




GUCCACUUA CCUGAGGA













2798




AGGGGACA CUGAUGA X GAA AUUCAUUU




AAAUGAAUU UGUCCCCU













2799




UAGGGGAC CUGAUGA X GAA AAUUCAUU




AAUGAAUUU GUCCCCUA













2802




UUGUAGGG CUGAUGA X GAA ACAAAUUC




GAAUUUGUC CCCUACAA













2807




UGGUCUUG CUGAUGA X GAA AGGGGACA




UGUCCCCUA CAAGACCA













2828




CUUGACGG CUGAUGA X GAA AUCGUGCC




GGCACGAUU CCGUCAAG













2829




CCUUGACG CUGAUGA X GAA AAUCGUGC




GCACGAUUC CGUCAAGG













2833




UUUCCCUU CUGAUGA X GAA ACGGAAUC




GAUUCCGUC AAGGGAAA













2846




CUCCAACG CUGAUGA X GAA AGUCUUUC




GAAAGACUA CGUUGGAG













2850




AUUGCUCC CUGAUGA X GAA ACGUAGUC




GACUACGUU GGAGCAAU













2859




UCCACAGG CUGAUGA X GAA AUUGCUCC




GGAGCAAUC CCUGUGGA













2869




CCGUUUCA CUGAUGA X GAA AUCCACAG




CUGUGGAUC UGAAACGG













2882




UGCUGUCC CUGAUGA X GAA AGCGCCGU




ACGGCGCUU GGACAGCA













2892




CUACUGGU CUGAUGA X GAA AUGCUGUC




GACAGCAUC ACCAGUAG













2899




GCUCUGGC CUGAUGA X GAA ACUGGUGA




UCACCAGUA GCCAGAGC













2909




AGCUGGCU CUGAUGA X GAA AGCUCUGG




CCAGAGCUC AGCCAGCU













2918




CAAAUCCA CUGAUGA X GAA AGCUGGCU




AGCCAGCUC UGGAUUUG













2924




CCUCCACA CUGAUGA X GAA AUCCAGAG




CUCUGGAUU UGUGGAGG













2925




UCCUCCAC CUGAUGA X GAA AAUCCAGA




UCUGGAUUU GUGGAGGA













2939




CACUGAGG CUGAUGA X GAA ACUUCUCC




GGAGAAGUC CCUCAGUG













2943




ACAUCACU CUGAUGA X GAA AGGGACUU




AAGUCCCUC AGUGAUGU













2952




UCUUCUUC CUGAUGA X GAA ACAUCACU




AGUGAUGUA GAAGAAGA













2968




AUCUUCAG CUGAUGA X GAA AGCUUCCU




AGGAAGCUC CUGAAGAU













2977




CUUAUACA CUGAUGA X GAA AUCUUGAG




CUGAAGAUC UGUAUAAG













2981




AGUCCUUA CUGAUGA X GAA ACAGAUCU




AGAUCUGUA UAAGGACU













2983




GAAGUCCU CUGAUGA X GAA AUACAGAU




AUCUGUAUA AGGACUUC













2990




AGGUCAGG CUGAUGA X GAA AGUCCUUA




UAAGGACUU CCUGACCU













2991




AAGGUCAG CUGAUGA X GAA AAGUCCUU




AAGGACUUC CUGACCUU













2999




GAUGCUCC CUGAUGA X GAA AGGUCAGG




CCUGACCUU GGAGCAUC













3007




ACAGAUGA CUGAUGA X GAA AUGCUCCA




UGGAGCAUC UCAUCUGU













3009




UAACAGAU CUGAUGA X GAA AGAUGCUC




GAGCAUCUC AUCUGUUA













3012




CUGUAACA CUGAUGA X GAA AUGAGAUG




CAUCUCAUC UGUUACAG













3016




GAAGCUGU CUGAUGA X GAA ACAGAUGA




UCAUCUGUU ACAGCUUC













3017




GGAAGCUG CUGAUGA X GAA AACAGAUG




CAUCUGUUA CAGCUUCC













3023




CCAGUGGG CUGAUGA X GAA AGCUGUAA




UUACAGCUU CCAAGGGG













3024




GCCACUUG CUGAUGA X GAA AAGCUGUA




UACAGCUUC CAAGUGGC













3034




CAUGCCCU CUGAUGA X GAA AGCCACUU




AAGUGGCUA AGGGCAUG













3047




AUGCCAAG CUGAUGA X GAA ACUCCAUG




CAUGGAGUU CUUGGCAU













3048




GAUGCCAA CUGAUGA X GAA AACUCCAU




AUGGAGUUC UUGGCAUC













3050




GCGAUGCC CUGAUGA X GAA AGAACUCC




GGAGUUCUU GGCAUCGC













3056




ACUUUCGC CUGAUGA X GAA AUGCCAAG




CUGGGCAUC GCGAAAGU













3067




CCUGUGGA CUGAUGA X GAA ACACUUUC




GAAAGUGUA UCCACAGG













3069




UCCCUGUG CUGAUGA X GAA AUACACUU




AAGGGUAUC CACAGGGA













3094




UAAGAGGA CUGAUGA X GAA AUUUCGUG




CAGAAAAUA UCCUCUUA













3096




GAUAAGAG CUGAUGA X GAA AUAUUUCG




CGAAAUAUC CUCUUAUC













3099




UCCGAUAA CUGAUGA X GAA AGGAUAUU




AAUAUCCUC UUAUCGGA













3101




UCUCCGAU CUGAUGA X GAA AGAGCAUA




UAUCCUCUU AUCGGAGA













3102




UUCUCCGA CUGAUGA X GAA AAGAGGAU




AUCCUCUUA UCGGAGAA













3104




UCUUCUCC CUGAUGA X GAA AUAAGAGG




CCUCUUAUC GGAGAAGA













3120




CAGAUUUU CUGAUGA X GAA ACCACGUU




AACGUGGUU AAAAUCUG













3121




ACAGAUUU CUGAUGA X GAA AACCACGU




ACGUGGUUA AAAUCUGU













3126




AAGUCACA CUGAUGA X GAA AUUUUAAC




GUUAAAAUC UGUGACUU













3134




CCAAGCCA CUGAUGA X GAA AGUCACAG




CUGUGACUU UGGCUUGG













3135




GCCAAGCC CUGAUGA X GAA AAGUCAGA




UGUGACUUU GGCUUGGC













3140




CCCGGGCC CUGAUGA X GAA AGCCAAAG




CUUUGGCUU GGCCCGGG













3151




UUUAUAAA CUGAUGA X GAA AUCCCGGG




CCCGGGAUA UUUAUAAA













3153




UCUUUAUA CUGAUGA X GAA AUAUCCCG




CGGGAUAUU UAUAAAGA













3154




AUCUUUAU CUGAUGA X GAA AAUAUCCC




GGGAUAUUU AUAAAGAU













3155




GAUCUUUA CUGAUGA X GAA AAAUAUCC




GGAUAUUUA UAAAGAUC













3157




UGGAUCUU CUGAUGA X GAA AUAAAUAU




AUAUUUAUA AAGAUCCA













3163




AUAAUCUG CUGAUGA X GAA AUCUUUAU




AUAAAGAUC CAGAUUAU













3169




UCUGACAU CUGAUGA X GAA AUCUGGAU




AUCCAGAUU AUGUCAGA













3170




UUCUGACA CUGAUGA X GAA AAUCUGGA




UCCAGAUUA UGUCAGAA













3174




CCUUUUCU CUGAUGA X GAA ACAUAAUC




GAUUAUGUC AGAAAAGG













3190




AGGGAGGC CUGAUGA X GAA AGCAUCUC




GAGAUGCUC GCCUCCCU













3195




UUCAAAGG CUGAUGA X GAA AGGCGAGC




GCUCGCCUC CCUUUGAA













3199




CCAUUUCA CUGAUGA X GAA AGGGAGGC




GCCUCCCUU UGAAAUGG













3200




UCCAUUUC CUGAUGA X GAA AAGGGAGG




CCUCCCUUU GAAAUGGA













3225




CUGUCAAA CUGAUGA X GAA AUUGUUUC




GAAACAAUU UUUGACAG













3226




UCUGUCAA CUGAUGA X GAA AAUUGUUU




AAACAAUUU UUGACAGA













3227




CUCUGUCA CUGAUGA X GAA AAAUUGUU




AACAAUUUU UGACAGAG













3228




ACUCUGUC CUGAUGA X GAA AAAAUUGU




ACAAUUUUU GACAGAGU













3239




GGAUUGUG CUGAUGA X GAA ACACUCUG




CAGAGUGUA CACAAUCC













3246




UCACUCUG CUGAUGA X GAA AUUGUGUA




UACACAAUC CAGAGUGA













3258




AAAGACCA CUGAUGA X GAA ACGUCACU




AGUGACGUC UGGUCUUU













3263




CACCAAAA CUGAUGA X GAA ACCAGACG




CGUCUGGUC UUUUGGUG













3265




AACACCAA CUGAUGA X GAA AGACCAGA




UCUGGUCUU UUGGUGUU













3266




AAACACCA CUGAUGA X GAA AAGACCAG




CUGGUCUUU UGGUGUUU













3267




AAAACACC CUGAUGA X GAA AAAGACCA




UGGUCUUUU GGUGUUUU













3273




CACAGCAA CUGAUGA X GAA ACACCAAA




UUUGGUGUU UUGCUGUG













3274




CCACAGCA CUGAUGA X GAA AACACCAA




UUGGUGUUU UGCUGUGG













3275




CCCACGGC CUGAUGA X GAA AAACACCA




UGGUGUUUU GCUGUGGG













3288




AAGGAAAA CUGAUGA X GAA AUUUCCCA




UGGGAAAUA UUUUCCUU













3290




CUAAGGAA CUGAUGA X GAA AUAUUUCC




GCAAAUAUU UUCCUUAG













3291




CCUAAGGA CUGAUGA X GAA AAUAUUUC




GAAAUAUUU UCCUUAGG













3292




ACCUAAGG CUGAUGA X GAA AAAUAUUU




AAAUAUUUU CCUUAGGU













3293




CACCUAAG CUGAUGA X GAA AAAAUAUU




AAUAUUUUC CUUAGGUG













3296




AAGCACCU CUGAUGA X GAA AGGAAAAU




AUUUUCCUU AGGUGCUU













3297




GAAGCACC CUGAUGA X GAA AAGGAAAA




UUUUCCUUA GGUGCUUC













3304




AUAUGGAG CUGAUGA X GAA AGCACCUA




UAGGUGCUU CUCCAUAU













3305




GAUAUGGA CUGAUGA X GAA AAGCACCU




AGGUGCUUC UCCAUAUC













3307




AGGAUAUG CUGAUGA X GAA AGAAGCAC




GUGCUUCUC CAUAUCCU













3311




CCCCAGGA CUGAUGA X GAA AUGGAGAA




UUCUCCAUA UCCUGGGG













3313




UACCCCAG CUGAUGA X GAA AUAUGGAG




CUCCAUAUC CUGGGGUA













3321




UCAAUCUU CUGAUGA X GAA ACCCCAGG




CCUGGGGUA AAGAUUGA













3327




UCUUCAUC CUGAUGA X GAA AUCUUUAC




GUAAAGAUU GAUGAAGA













3338




GCCUACAA CUGAUGA X GAA AUUCUUCA




UGAAGAAUU UUGUAGGC













3339




CGCCUACA CUGAUGA X GAA AAUUCUUC




GAAGAAUUU UGUAGGCG













3340




UCGCCUAC CUGAUGA X GAA AAAUUCUU




AAGAAUUUU GUAGGCGA













3343




CAAUCGCC CUGAUGA X GAA ACAAAAUU




AAUUUUGUA GGCGAUUG













3350




CUUCUUUC CUGAUGA X GAA AUCGCCUA




UAGGCGAUU GAAAGAAG













3364




CCUCAUUC CUGAUGA X GAA AGUUCCUU




AAGGAACUA GAAUGAGG













3382




UGUAGUAU CUGAUGA X GAA AUCAGGGG




CCCCUGAUU AUACUACA













3383




GUGUAGUA CUGAUGA X GAA AAUCAGGG




CCCUGAUUA UACUACAC













3385




UGGUGUAG CUGAUGA X GAA AUAAUCAG




CUGAUUAUA CUACACCA













3388




UUCUGGUG CUGAUGA X GAA AGUAUAAU




AUUAUACUA CACCAGAA













3401




UGGUCUGG CUGAUGA X GAA ACAUUUCU




AGAAAUGUA CCAGACCA













3439




GGGUCUCU CUGAUGA X GAA ACUGGGCU




AGCCCAGUC AGAGACCC













3452




ACUCUGAA CUGAUGA X GAA ACGUGGGU




ACCCACGUU UUCAGAGU













3453




AACUCUGA CUGAUGA X GAA AACGUGGG




CCCACGUUU UCAGAGUU













3454




CAACUCUG CUGAUGA X GAA AAACGUGG




CCACGUUUU CAGAGUUG













3455




CCAACUCU CUGAUGA X GAA AAAACGUG




CACGUUUUC AGAGUUGG













3461




GUUCCACC CUGAUGA X GAA ACUCUGAA




UUCAGAGUU GGUGGAAC













3472




AUUUCCCA CUGAUGA X GAA AUGUUCCA




UGGAACAUU UGGGAAAU













3473




GAUUUCCC CUGAUGA X GAA AAUGUUCC




GGAACAUUU GGGAAAUC













3481




UUGCAAGA CUGAUGA X GAA AUUUCCCA




UGGGAAAUC UCUUGCAA













3483




GCUUGCAA CUGAUGA X GAA AGAUUUCC




GAAAAUCUC UUGCAAGC













3485




UAGCUUGC CUGAUGA X GAA AGAGAUUU




AAAUCUCUU GCAAGCUA













3493




CUGAGCAU CUGAUGA X GAA AGCUUGCA




UGCAAGCUA AUGCUCAG













3499




AUCCUGCU CUGAUGA X GAA AGCAUUAG




CUAAUGCUC AGCAGGAU













3518




GAACAAUG CUGAUGA X GAA AGUCUUUG




CAAAGACUA CAUUGUUC













3522




GGAAGAAC CUGAUGA X GAA AUGUAGUC




GACUACAUU GUUCUUCC













3525




AUCGGAAG CUGAUGA X GAA ACAAUGUA




UACAUUGUU CUUCCGAU













3526




UAUCGGAA CUGAUGA X GAA AACAAUGU




ACAUUGUUC UUCCGAUA













3528




GAUAUCGG CUGAUGA X GAA AGAACAAU




AUUGUUCUU CCGAUAUC













3529




UGAUAUCG CUGAUGA X GAA AAGAACAA




UUGUUCUUC CGAUAUCA













3534




GUCUCUGA CUGAUGA X GAA AUCGGAAG




CUUCCGAUA UCAGAGAC













3536




AAGUCUCU CUGAUGA X GAA AUAUCGGA




UCCGAUAUC AGAGACUU













3544




CAUGCUCA CUGAUGA X GAA AGUCUCUG




CAGAGACUU UGAGCAUG













3545




CCAUGCUC CUGAUGA X GAA AAGUCUCU




AGAGACUUU GAGCAUGG













3562




GAGUCCAG CUGAUGA X GAA AUCCUCUU




AAGAGGAUU CUGGACUC













3563




AGAGUCCA CUGAUGA X GAA AAUCCUCU




AGAGGAUUC UGGACUCU













3570




GGCAGAGA CUGAUGA X GAA AGUCCAGA




UCUGGACUC UCUCUGCC













3572




UAGGCAGA CUGAUGA X GAA AGAGUCCA




UGGACUCUC UCUGCCUA













3574




GGUAGGCA CUGAUGA X GAA AGAGAGUC




GACUCUCUC UGCCUACC













3580




AGGUGAGG CUGAUGA X GAA AGGCAGAG




CUCUGCCUA CCUCACCU













3584




AAACAGGU CUGAUGA X GAA AGGUAGGC




GCCUACCUC ACCUGUUU













3591




AUACAGGA CUGAUGA X GAA ACAGGUGA




UCACCUGUU UCCUGUAU













3592




CAUACAGG CUGAUGA X GAA AACAGGUG




CACCUGUUU CCUGUAUG













3593




CCAUACAG CUGAUGA X GAA AAACAGGU




ACCUGUUUC CUGUAUGG













3598




CUCCUCCA CUGAUGA X GAA ACAGGAAA




UUUCCUGUA UGGAGGAG













3615




GGGUCACA CUGAUGA X GAA ACUUCCUC




GAGGAAGUA UGUGACCC













3629




CAUAAUGG CUGAUGA X GAA AUUUGGGG




CCCCAAAUU CCAUUAUG













3630




UCAUAAUG CUGAUGA X GAA AAUUUGGG




CCCAAAUUC CAUUAUGA













3634




GUUGUCAU CUGAUGA X GAA AUGGAAUU




AAUUCCAUU AUGACAAC













3635




UGUUGUCA CUGAUGA X GAA AAUGGAAU




AUUCCAUUA UGACAACA













3654




UACUGACU CUGAUGA X GAA AUUCCUGC




GCAGGAAUC AGUCAGUA













3658




CAGAUACU CUGAUGA X GAA ACUGAUUC




GAAUCAGUC AGUAUCUG













3662




UCUGCAGA CUGAUGA X GAA ACUGACUG




CAGUGAGUA UCUGCAGA













3664




GUUCUGCA CUGAUGA X GAA AUACUGAC




GUCAGUAUC UGCAGAAC













3676




CUUUCGCU CUGAUGA X GAA ACUGUUCU




AGAACAGUA AGCGAAAG













3702




AAUGUUUU CUGAUGA X GAA ACACUCAC




GUGAGUGUA AAAACAUU













3710




UAUCUUCA CUGAUGA X GAA AUGUUUUU




AAAAACAUU UGAAGAUA













3711




AUAUCUUC CUGAUGA X GAA AAUGUUUU




AAAACAUUU GAAGAUAU













3718




UAACGGGA CUGAUGA X GAA AUCUUCAA




UUGAAGAUA UCCCGUUA













3720




UCUAACGG CUGAUGA X GAA AUAUCUUC




GAAGAUAUC CCGUUAGA













3725




GUUCUUCU CUGAUGA X GAA ACGGGAUA




UAUCCCGUU AGAAGAAC













3726




GGUUCUUC CUGAUGA X GAA AACGGGAU




AUCCCGUUA GAAGAACC













3741




AUUACUUU CUGAUGA X GAA ACUUCUGG




CCAGAAGUA AAAGUAAU













3747




UCUGGGAU CUGAUGA X GAA ACUUUUAC




GUAAAAGUA AUCCCAGA













3750




UCAUCUGG CUGAUGA X GAA AUUACUUU




AAAGUAAUC CCAGAUGA













3778




AAGAACCA CUGAUGA X GAA ACCACUGU




ACAGUGGUA UGGUUCUU













3783




GAGGCAAG CUGAUGA X GAA ACCAUACC




GGUAUGGUU CUUGCCUC













3784




UGAGGCAA CUGAUGA X GAA AACCAUAC




GUAUGGUUC UUGCCUCA













3786




UCUGAGGC CUGAUGA X GAA AGAACCAU




AUGGUUCUU GCCUCAGA













3791




GCUCUUCU CUGAUGA X GAA AGGCAAGA




UCUUGCCUC AGAAGAGC













3808




GUCUUCCA CUGAUGA X GAA ACUUUUCA




UGAAAACUU UGGAAGAC













3809




UGUCUUCC CUGAUGA X GAA AAGUUUUC




GAAAACUUU GGAAGACA













3827




AUGGAGAU CUGAUGA X GAA AUUUGGUU




AACCAAAUU AUCUCCAU













3828




GAUGGAGA CUGAUGA X GAA AAUUUGGU




ACCAAAUUA UCUCCAUC













3830




AAGAUGGA CUGAUGA X GAA AUAAUUUG




CAAAUUAUC UCCAUCUU













3832




AAAAGAUG CUGAUGA X GAA AGAUAAUU




AAUUAUCUC CAUCUUUU













3836




CACCAAAA CUGAUGA X GAA AUGGAGAU




AUCUCCAUC UUUUGGUG













3838




UCCACCAA CUGAUGA X GAA AGAUGGAG




CUCCAUCUU UUGGUGGA













3839




UUCCACCA CUGAUGA X GAA AAGAUGCA




UCCAUCUUU UGGUGGAA













3840




AUUCCACC CUGAUGA X GAA AAAGAUGG




CCAUCUUUU GGUGGAAU













3872




AUGCCACA CUGAUGA X GAA ACUCCCUG




CAGGGAGUC UGUGGCAU













3881




AGCCUUCA CUGAUGA X GAA AUGCCACA




UGUGGCAUC UGAAGGCU













3890




UCUGGUUU CUGAUGA X GAA AGCCUUCA




UGAAGGCUC AAACCAGA













3908




CGGACUGG CUGAUGA X GAA AGCCGCUU




AAGCGGCUA CCAGUCCG













3914




GAUAUCCG CUGAUGA X GAA ACUGGUAG




CUACCAGUC CGGAUAUC













3920




CGGAGUGA CUGAUGA X GAA AUCCGCAC




GUCCGGAUA UCACUCCG













3922




AUCGGAGU CUGAUGA X GAA AUAUCCGG




CCGGAUAUC ACUCCGAU













3926




UGUCAUCG CUGAUGA X GAA AGUGAUAU




AUAUCACUC CGAUGACA













3950




CACUGGAG CUGAUGA X GAA ACACGGUG




CACCGUGUA CUCCAGUG













3953




CCUCACUG CUGAUGA X GAA AGUACACG




CGUGUACUC CAGUGAGG













3972




AGCUUUAA CUGAUGA X GAA AGUUCUGC




GCAGAACUU UUAAAGCU













3973




CAGCUUUA CUGAUGA X GAA AAGUUCUG




CAGAACUUU UAAAGCUG













3974




UCAGCUUU CUGAUGA X GAA AAAGUUCU




AGAACUUUU AAAGCUGA













3975




AUCAGCUU CUGAUGA X GAA AAAAGUUC




GAACUUUUA AAGCUGAU













3984




CCAAUCUC CUGAUGA X GAA AUCAGCUU




AAGCUGAUA GAGAUGGG













3990




UGGACUCC CUGAUGA X GAA AUCUCUAU




AUAGAGAUU GGAGUGCA













4006




GGCUGUGC CUGAUGA X GAA ACCGGUUU




AAACCGGUA GCACAGCC













4020




GGCUGGAG CUGAUGA X GAA AUCUGGGC




GCCCAGAUU CUCCAGCC













4021




AGGCUGGA CUGAUGA X GAA AAUCUGGG




CCCAGAUUC UCCAGCCU













4023




UCAGGCUG CUGAUGA X GAA AGAAUCUG




CAGAUUCUC CAGCCUGA













4052




CAGGAGGA CUGAUGA X GAA AGCUCAGU




ACUGAGCUC UCCUCCUG













4054




AACAGGAG CUGAUGA X GAA AGAGGUCA




UGAGCUCUC CUCCUGUU













4057




UUAAACAG CUGAUGA X GAA AGGAGAGC




GCUCUCCUC CUGUUUAA













4062




UCCUUUUA CUGAUGA X GAA ACGGGAGG




CCUCCUGUU UAAAAGGA













4063




UUCCUUUU CUGAUGA X GAA AACAGGAG




CUCCUGUUU AAAAGGAA













4064




CUUCCUUU CUGAUGA X GAA AAACAGGA




UCCUGUUUA AAAGGAAG













4076




GGGGUGUG CUGAUGA X GAA AUGCUUCC




GGAAGCAUC CACACCCC













4089




AUGUCCGG CUGAUGA X GAA AGUUGGGG




CCCCAACUC CCGGACAU













4098




UCUCAUGU CUGAUGA X GAA AUGUCCGG




CCGGACAUC ACAUGAGA













4110




UCUGAGCA CUGAUGA X GAA ACCUCUCA




UGAGAGGUC UGCUCAGA













4115




CAAAAUCU CUGAU&A X GAA AGCAGACC




GGUCUGCUC AGAUUUUG













4120




CACUUCAA CUGAUGA X GAA AUCUGAGC




GCUCAGAUU UUGAAGUG













4121




ACAUCUUA CUGAUGA X GAA AAUCUGAG




CUGAGAUUU UGAAGUGU













4122




AACACUUC CUGAUGA X GAA AAAUCUGA




UCAGAUUUU GAAGUGUU













4130




GAAAGAAC CUGAUGA X GAA ACACUUCA




UGAAGUGUU GUUCUUUC













4133




GUGGAAAG CUGAUGA X GAA ACAACACU




AGUGUUGUU CUUUCCAC













4134




GGUGGAAA CUGAUGA X GAA AACAACAC




GUGUUGUUC UUUCCACC













4136




CUGGUGGA CUGAUGA X GAA AGAACAAC




GUUGUUCUU UCCACCAG













4137




GCUGGUGG CUGAUGA X GAA AAGAACAA




UUGUUCUUU CCACCAGC













4138




UGCUGGUG CUGAUGA X GAA AAAGAACA




UGUUCUUUC CACCAGCA













4153




AAUGCGGC CUGAUGA X GAA ACUUCCUG




CAGGAAGUA GCCGCAUU













4161




GAAAAUCA CUGAUGA X GAA AUGCGGCU




AGCCGCAUU UGAUUUUC













4162




UGAAAAUC CUGAUGA X GAA AAUGCGGC




GCCGCAUUU GAUUUUCA













4166




GAAAUGAA CUGAUGA X GAA AUCAAAUG




CAUUUGAUU UUCAUUUC













4167




CGAAAUGA CUGAUGA X GAA AAUCAAAU




AUUUGAUUU UCAUUUCG













4168




UCGAAAUG CUGAUGA X GAA AAAUCAAA




UUUGAUUUU CAUUUCGA













4169




GUCGAAAU CUGAUGA X GAA AAAAUCAA




UUGAUUUUC AUUUCGAC













4172




GUUGUCGA CUGAUGA X GAA AUGAAAAU




AUUUUCAUU UCGACAAC













4173




UGUUGUCG CUGAUGA X GAA AAUGAAAA




UUUUCAUUU CGACAACA













4174




CUGUUGUC CUGAUGA X GAA AAAUGAAA




UUUCAUUUC GACAACAG













4194




UGGAGUCC CUGAUGA X GAA AGGUCCUU




AAGGACCUC GGACUGCA













4214




GCCUAGAA CUGAUGA X GAA AGCUGGCU




AGCCAGCUC UUCUAGGC













42 16




AAGCCUAG CUGAUGA X GAA AGAGCUGG




CCAGCUCUU CUAGGCUU













4217




CAAGCCUA CUGAUGA X GAA AAGAGCUG




CAGCUCUUC UAGGCUUG













4219




CACAAGCC CUGAUGA X GAA AGAAGAGC




GCUCUUCUA GGCUUGUG











Where “X” represents stem II region of a HH ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20 3252). The length of stem II may be ≧2 base-pairs.





















TABLE V











Human KDR VEGF Receptor-Hairpin Ribozyme and Substrate Sequences













nt.








Position




Hairpin Ribozyme Sequence




Substrate









  11




CGACGGCC AGAA GCACCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGGUGCU GCU GGCCGUCG













  18




CACAGGGC AGAA GCCAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUGGCC GUC GCCCUGUG













  51




CCCACAGA AGAA GCCCGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCGGGCC GCC UCUGUGGG













  86




UGAGCCUG AGAA GAUCAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUGAUCU GCC CAGGCUCA













 318




GAGGCCAA AGAA GUUUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAAACU GAC UUGGCCUC













 358




AAAUGGAG AGAA GUAAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAUUACA GAU CUCCAUUU













 510




CUGUUACC AGAA GGAACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUUCCU GAU GGUAACAG













 623




ACAUAAUA AGAA GGUAAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUUACCA GUC UAUUAUGU













 683




UUCCAUGA AGAA GACUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAGUCC GUC UCAUGGAA













 705




UUUUCUCC AGAA GAUAGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACUAUCU GUU GGAGAAAA













 833




CACUCCCA AGAA GGGUUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAACCCA GUC UGGGAGUG













 932




UCUUGGUC AGAA GCCCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUGGGCU GAU GACCAAGA













1142




CCAUAAUC AGAA GUACAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUGUACU GAC GAUUAUGG













1259




UCUCACCA AGAA GGGGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACCCCA GAU UGGUGAGA













1332




AUGGCAUA AGAA GUACAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUGUACG GUC UAUGCCAU













1376




CUUCCUCC AGAA GCCAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUUGGCA GUU GGAGGAAG













1413




GUCACUGA AGAA GGUUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCAAGCU GUC UCAGUGAC













1569




UUGUACAA AGAA GACACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUGUCA GCU UUGUACAA













1673




GCUCAGUG AGAA GCAUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACAUGCA GCC CACUGAGC













1717




AAACGUAG AGAA GUCUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCAGACA GAU CUACGUUU













1760




UUGGCAGA AGAA GUGGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCCCACA GCC UCUGCCAA













1797




UUCUUGCA AGAA GGUGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACACCU GUU UGCAAGAA













1918




UUGAGCAA AGAA GACAUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UAUGUCU GCC UUGCUCAA













1967




GGACUGUG AGAA GCCUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCAGGCA GCU CACAGUCC













1974




CGCUCUAG AGAA GUGAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUCACA GUC CUAGAGCG













2021




UACUUGUC AGAA GAUUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGAAUCA GAC GACAAGUA













2084




ACCACAUG AGAA GUGGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCCACA GAU CAUGUGGU













2418




GGGAGUUC AGAA GGAUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCAUCCA GAU GAACUCCC













2453




CAUCAUAA AGAA GUCGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AACGACU GCC UUAUGAUG













2492




CUAGGUUC AGAA GGUCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAGACCG GCU GAACCUAG













2547




CCAAAGGC AGAA GCUUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAAGCA GAU GCCUUUGG













2765




GGUAAGUG AGAA GGUUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAAACCU GUC CACUUACC













2914




AAAUCCAG AGAA GGCUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCAGCCA GCU CUGGAUUU













2993




GCUCCAAG AGAA GGAAGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACUUCCU GAC CUUGGAGC













3019




CACUUGGA AGAA GUAACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUUACA GCU UCCAAGUG













3165




CUGACAUA AGAA GGAUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGAUCCA GAU UAUGUCAG













3378




GUAGUAUA AGAA GGGGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCCCCU GAU UAUACUAC













3404




CCAGCAUG AGAA GGUACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUACCA GAC CAUGCUGG













3418




CCCGUGCC AGAA GUCCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGGACU GCU GGCACGGG













3575




GUGAGGUA AGAA GAGAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUCUCU GCC UACCUCAC













3588




AUACAGGA AGAA GGUGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCACCU GUU UCCUGUAU













3689




CACUCACA AGAA GGCUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGAGCCG GCC UGUGAGUG













3753




UGGUUGUC AGAA GGGAUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAUCCCA GAU GACAACCA













3764




CACUGUCC AGAA GGUUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACAACCA GAC GGACAGUG













3911




GAUAUCCG AGAA GGUAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUACCA GUC CGGAUAUC













3927




UCUGUGUC AGAA GAGUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCACUCC GAU GACACAGA













4011




AGAAUCUG AGAA GUGCUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UAGCACA GCC CAGAUUCU













4016




GCUGGAGA AGAA GGGCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAGCCCA GAU UCUCCAGC













4025




CCGUGUCA AGAA GGAGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUCUCCA GCC UGACACGG













4059




UCCUUUUA AGAA GGAGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCCUCCU GUU UAAAAGGA













4111




AAAAUCUG AGAA GACCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAGGUCU GCU CAGAUUUU













4116




ACUUCAAA AGAA GAGGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGCUCA GAU UUUGAAGU













4195




UCCCUGCA AGAA GAGGUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GACCUCG GAC UGCAGGGA













4210




CCUAGAAG AGAA GGCUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAGCCA GCU CUUCUAGG






















TABLE VI











Mouse flk-1 VEGF Receptor-Hammerhead Ribozyme and






Substrate sequence













nt. Position




HH Ribozyme Sequence




Substrate









  13




CCGUACCC CUGAUGA X GAA AUUCGCCC




GGGCGAAUU GGGUACGG













  18




GGGUCCCG CUGAUGA X GAA ACCCAAUU




AAUUGGGUA CGGGACCC













  31




UCGACCUC CUGAUGA X GAA AGGGGGGU




ACCCCCCUC GAGGUCGA













  37




AUACCGUC CUGAUGA X GAA ACCUqGAG




CUCGAGGUC GACGGUAU













  44




CUUAUCGA CUGAUGA X GAA ACCGUCGA




UCGACGGUA UCCAUAAG













  46




AGCUUAUC CUGAUGA X GAA AUACCGUC




GACGGUAUC GAUAAGCU













  50




AUCAAGCU CUGAUGA X GAA AUCGAUAC




GUAUCGAUA AGCUUGAU













  55




UCGAUAUC CUGAUGA X GAA AGCUUAUC




GAUAAGCUU GAUAUCGA













  59




GAAUUCGA CUGAUGA X GAA AUCAAGCU




AGCUUGAUA UCGAAUUC













  61




CCGAAUUC CUGAUGA X GAA AUAUCAAG




CUUGAUAUC GAAUUCGG













  66




UGGGCCCG CUGAUGA X GAA AUUCGAUA




UAUCGAAUU CGGGCCCA













  67




CUGGGCCC CUGAUGA X GAA AAUUCGAU




AUCGAAUUC GGGCCCAG













  83




GGCUGCGG CUGAUGA X GAA ACACAGUC




GACUGUGUC CCGCAGCC













  97




AGCCAGGU CUGAUGA X GAA AUCCCGGC




GCCGGGAUA ACCUGGCU













 114




GUCCGCGG CUGAUGA X GAA AUCGGGUC




GACCCGAUU CCGCGGAC













 115




UGUCCGCG CUGAUGA X GAA AAUCGGGU




ACCCGAUUC CGCGGACA













 169




ACCGGGGA CUGAUGA X GAA AGCGCGGG




CCCGCGCUC UCCCCGGU













 171




AGACCGGG CUGAUGA X GAA AGAGCGCG




CGCGCUCUC CCCGGUCU













 178




CAGCGCAA CUGAUGA X GAA ACCGGGGA




UCCCCGGUC UUGCGCUG













 180




CGCAGCGC CUGAUGA X GAA AGACCGGG




CCCGGUCUU GCGCUGCG













 197




AGAGGCGG CUGAUGA X GAA AUGGCCCC




GGGGCCAUA CCGCCUCU













 204




AAGUCACA CUGAUGA X GAA AGGCGGUA




UACCGCCUC UGUGACUU













 212




CCGCAAAG CUGAUGA X GAA AGUCACAG




CUGUGACUU CUUUGCGG













 213




CCCGCAAA CUGAUGA X GAA AAGUCACA




UGUGACUUC UUUGCGGG













 215




GGCCCGCA CUGAUGA X GAA AGAAGUCA




UGACUUCUU UGCGGGCC













 216




UGGCCCGC CUGAUGA X GAA AAGAAGUC




GACUUCUUU GCGGGCCA













 241




CAGGCACA CUGAUGA X GAA ACUCCUUC




GAAGGAGUC UGUGCCUG













 262




UGGGCACA CUGAUGA X GAA AGCCCAGU




ACUGGGCUC UGUGCCCA













 306




GCGACAGC CUGAUGA X GAA AGCAGCGC




GCGCUGCUA GCUGUCGC













 312




CACAGAGC CUGAUGA X GAA ACAGCUAG




CUAGCUGUC GCUCUGUG













 316




GAACCACA CUGAUGA X GAA AGCGACAG




CUGUCGCUC UGUGGUUC













 323




CCACGCGG CUGAUGA X GAA ACCACAGA




UCUGUGGUU CUGCGUGG













 324




UCCACGCA CUGAUGA X GAA AACCACAG




CUGUGGUUC UGGGUGGA













 347




AACCCACA CUGAUGA X GAA AGGCGGCU




AGCCGCCUC UGUGGGUU













 355




GCCAGUCA CUGAUGA X GAA ACCCACAG




CUGUGGGUU UGACUGGC













 356




CGCCAGUC CUGAUGA X GAA AACCCACA




UGUGGGUUU GACUGGCG













 367




AUGGAGAA CUGAUGA X GAA AUCGCCAG




CUGGCGAUU UUCUCCAU













 368




GAUGGAGA CUGAUGA X GAA AAUCGCCA




UGGCGAUUU UCUCCAUC













 369




GGAUGGAG CUGAUGA X GAA AAAUCGCC




GGCGAUUUU CUCCAUCC













 370




GGGAUGGA CUGAUGA X GAA AAAAUCGC




GCGAUUUUC UCCAUCCC













 372




GGGGGAUG CUGAUGA X GAA AGAAAAUC




GAUUUUCUC CAUCCCCC













 376




CUGGGGGG CUGAUGA X GAA AUGGAGAA




UUCUCCAUC CCCCCAAG













 387




UGUGUGCU CUGAUGA X GAA AGCUUGGG




CCCAAGCUC AGCACACA













 405




AUUGUCAG CUGAUGA X GAA AUGUCUUU




AAAGACAUA CUGACAAU













 414




UUUGCCAA CUGAUGA X GAA AUGGUCAG




CUGACAAUU UUGGCAAA













 415




AUUUGCCA CUGAUGA X GAA AAUUGUCA




UGACAAUUU UGGCAAAU













 416




UAUUUGCC CUGAUGA X GAA AAAUUGUC




GACAAUUUU GGCAAAUA













 424




AAGGGUUG CUGAUGA X GAA AUUUGCCA




UGGCAAAUA CAACCCUU













 432




GUAAUCUG CUGAUGA X GAA ACGGUUGU




ACAACCCUU CAGAUUAC













 433




AGUAAUCU CUGAUGA X GAA AAGGGUUG




CAACCCUUC AGAUUACU













 438




CUGCAAGU CUGAUGA X GAA AUCUGAAG




CUUCAGAUU ACUUGCAG













 439




CCUGCAAG CUGAUGA X GAA AAUCUGAA




UUCAGAUUA CUUGCAGG













 442




UCCCCUGC CUGAUGA X GAA AGUAAUCU




AGAUUACUU GCAGGGGA













 471




UUGGGCCA CUGAUGA X GAA AGCCAGUC




GACUGGCUU UGGCCCAA













 472




AUUGGGCC CUGAUGA X GAA AAGCCAGU




ACUGGCUUU GGCCCAAU













 484




AUCACGCU CUGAUGA X GAA AGCAUUGG




CCAAUGCUC AGCGUGAU













 493




UUCCUCAG CUGAUGA X GAA AUCACGCU




AGCGUGAUU CUGACGAA













 494




UUUCCUCA CUGAUGA X GAA AAUCACGC




GCGUGAUUC UGAGGAAA













 507




GUCACCAA CUGAUGA X GAA ACCCUUUC




GAAAGGGUA UUGGUGAC













 509




CAGUCACC CUGAUGA X GAA AUACCCUU




AAGGGUAUU GGUGACUG













 538




GCAGAAGA CUGAUGA X GAA ACUGUCAC




GUGACAGUA UCUUCUGC













 540




UUGCAGAA CUGAUGA X GAA AUACUGUC




GACAGUAUC UUCUGCAA













 542




UUUUGCAG CUGAUGA X GAA AGAUACUG




CAGUAUCUU CUGCAAAA













 543




GUUUUGCA CUGAUGA X GAA AAGAUACU




AGUAUCUUC UGGAAAAC













 555




GGAAUGGU CUGAUGA X GAA AGUGUUUU




AAAACACUC ACCAUUCC













 561




ACCCUGGG CUGAUGA X GAA AUGGUGAG




CUCACCAUU CCCAGGGU













 562




CACCCUGG CUGAUGA X GAA AAUGGUGA




UCACCAUUC CCAGGGUG













 573




UCAUUUCC CUGAUGA X GAA ACCACCCU




AGGGUGGUU GGAAAUGA













 583




GGCUCCAG CUGAUGA X GAA AUCAUUUC




GAAAUGAUA CUGGAGCC













 593




AGCACUUG CUGAUGA X GAA AGGCUCCA




UGGAGCCUA CAAGUGCU













 602




CCCGGUAC CUGAUGA X GAA AGCACUUG




CAAGUGCUC GUACCGGG













 605




CGUCCCGG CUGAUGA X GAA ACGAGCAC




GUGCUCGUA CCGGGACG













 615




GCUAUGUC CUGAUGA X GAA ACGUCCCG




CGGGACGUC GACAUAGC













 621




GUGGAGGC CUGAUGA X GAA AUGUCGAC




GUCGACAUA GCCUCCAC













 626




AAACAGUG CUGAUGA X CAA AGGCUAUG




CAUAGCCUC CACUGUUU













 633




UAGACAUA CUGAUGA X GAA ACAGUGGA




UCCACUGUU UAUGUCUA













 634




AUAGACAU CUGAUGA X GAA AACAGUGG




CCACUGUUU AUGUCUAU













 635




CAUAGACA CUGAUGA X GAA AAACAGUG




CACUGUUUA UGUCUAUG













 639




CGAACAUA CUGAUGA X GAA ACAUAAAC




GUUUAUGUC UAUGUUCG













 641




CUCGAACA CUGAUGA X GAA AGACAUAA




UUAUGUCUA UGUUCGAG













 645




UAAUCUCG CUGAUGA X GAA ACAUAGAC




GUCUAUGUU CGAGAUUA













 646




GUAAUCUC CUGAUGA X GAA AACAUAGA




UCUAUGUUC GAGAUUAC













 652




UGAUCUGU CUGAUGA X GAA AUCUCGAA




UUCGAGAUU ACAGAUCA













 653




GUGAUCUG CUGAUGA X GAA AAUCUCGA




UCGAGAUUA CAGAUCAC













 659




UGAAUGGU CUGAUGA X GAA AUCUGUAA




UUACAGAUC ACCAUUCA













 665




AGGCGAUG CUGAUGA X GAA AUGGUGAU




AUCACCAUU CAUCGCCU













 666




GAGGCGAU CUGAUGA X GAA AAUGGUGA




UCACCAUUC AUCGCCUC













 669




ACAGAGGC CUGAUGA X GAA AUGAAUGG




CCAUUCAUC GCCUCUGU













 674




CACUGACA CUGAUGA X GAA AGGCGAUG




CAUCGCCUC UGUCAGUG













 678




UGGUCACU CUGAUGA X GAA ACAGAGGC




GCCUCGGUC AGUGACCA













 696




AUGUACAC CUGAUGA X GAA AUGCCAUG




CAUGGCAUC GUGUACAU













 701




CGGUGAUG CUGAUGA X GAA ACACGAUG




CAUCGUGUA CAUCACCG













 705




UUCUCGGU CUGAUGA X GAA AUGUACAC




GUGUACAUC ACCGAGAA













 735




CGGCAGGG CUGAUGA X GAA AUCACCAC




GUGGUGAUC CCCUGCCG













 749




UUGAAAUC CUGAUGA X GAA ACCCUCGG




CCGAGGGUC GAUUUCAA













 753




AGGUUUGA CUGAUGA X GAA AUCGACCC




GGGUCGAUU UCAAACCU













 754




GAGGUUUG CUGAUGA X GAA AAUCGACC




GGUCGAUUU CAAACCUC













 755




UGAGGUUU CUGAUGA X GAA AAAUCGAC




GUCGAUUUC AAACCUCA













 762




GACACAUU CUGAUGA X GAA AGGUUUGA




UCAAACCUC AAUGUGUC













 770




CGCAAAGA CUGAUGA X GAA ACACAUUG




CAAUGUGUC UCUUUGCG













 772




AGCGCAAA CUGAUGA X GAA AGACACAU




AUGUGUCUC UUUGCGCU













 774




CUAGCGCA CUGAUGA X GAA AGAGACAC




GUGUCUCUU UGCGCUAG













 775




CCUAGCGC CUGAUGA X GAA AAGAGACA




UGUCUCUUU GCGCUAGG













 781




UGGAUACC CUGAUGA X GAA AGCGCAAA




UUUGCGCUA GGUAUCCA













 785




UUUCUGGA CUGAUGA X GAA ACCUAGCG




CGCUAGGUA UCCAGAAA













 787




CUUUUCUG CUGAUGA X GAA AUACCUAG




CUAGGUAUC CAGAAAAG













 800




CCGGAACA CUGAUGA X GAA AUCUCUUU




AAAGAGAUU UGUUCCGG













 801




UCCGGAAC CUGAUGA X GAA AAUCUCUU




AAGAGAUUU GUUCCGGA













 804




CCAUCCGG CUGAUGA X GAA ACAAAUCU




AGAUUUGUU CCGGAUGG













 805




UCCAUCCG CUGAUGA X GAA AACAAAUC




GAUUUGUUC CGGAUGGA













 822




UCCCAGGA CUGAUGA X GAA AUUCUGUU




AAGAGAAUU UCCUGGGA













 823




GUCCCAGG CUGAUGA X GAA AAUUCUGU




ACAGAAUUU CCUGGGAC













 824




UGUCCCAG CUGAUGA X GAA AAAUUCUG




CAGAAUUUC CUGGGACA













 840




GUAAAGCC CUGAUGA X GAA AUCUCGCU




AGCGAGAUA GGCUUUAC













 845




GGAGAGUA CUGAUGA X GAA AGCCUAUC




GAUAGGCUU UACUCUCC













 846




GGGAGAGU CUGAUGA X GAA AAGCCUAU




AUAGGCUUU ACUCUCCC













 847




GGGGAGAG CUGAUGA X GAA AAAGCCUA




UACGCUUUA CUCUCCCC













 850




ACUGGGGA CUGAUGA X GAA AGUAAAGC




GCUUUACUC UCCCCAGU













 852




UAACUGGG CUGAUGA X GAA AGAGUAAA




UUUACUCUC CCCAGUUA













 859




GAUCAUGU CUGAUGA X GAA ACUGGGGA




UCCCCAGUU ACAUGAUC













 860




UGAUCAUG CUGAUGA X GAA AACUGGGG




CCCCAGUUA CAUGAUCA













 867




GCAUAGCU CUGAUGA X GAA AUCAUGUA




UACAUGAUC AGCUAUGC













 872




UGCCGGCA CUGAUGA X GAA AGCUGAUC




GAUCAGCUA UGCCGGCA













 885




UCACAGAA CUGAUGA X GAA ACCAUGCC




GGCAUGGUC UUCUGUGA













 887




CCUCACAG CUGAUGA X GAA AGACCAUG




CAUGGUCUU CUGUGAGG













 888




GCCUCACA CUGAUGA X GAA AAGACCAU




AUGGUCUUC UGUGAGGC













 903




UCAUCAUU CUGAUGA X GAA AUCUUUGC




GCAAAGAUC AAUGAUGA













 917




UAGACUGA CUGAUGA X GAA AGGUUUCA




UGAAACCUA UCAGUCUA













 919




GAUAGACU CUGAUGA X GAA AUAGGUUU




AAACCUAUC AGUCUAUC













 923




ACAUGAUA CUGAUGA X GAA ACUGAUAG




CUAUCAGUC UAUCAUGU













 925




GUACAUGA CUGAUGA X GAA AGACUGAU




AUCAGUCUA UCAUGUAC













 927




AUGUACAU CUGAUGA X GAA AUAGACUG




CAGUCUAUC AUGUACAU













 932




CAACUAUG CUGAUGA X GAA ACAUGAUA




UAUCAUGUA CAUAGUUG













 936




ACCACAAC CUGAUGA X GAA AUGUACAU




AUGUACAUA GUUGUGGU













 939




ACAACCAC CUGAUGA X GAA ACUAUGUA




UACAUAGUU GUGGUUGU













 945




UAUCCUAC CUGAUGA X GAA ACCACAAC




GUUGUGGUU GUAGGAUA













 948




CUAUAUCC CUGAUGA X GAA ACAACCAC




GUGGUUGUA GGAUAUAG













 953




AAAUCCUA CUGAUGA X GAA AUCCUACA




UGUAGGAUA UAGGAUUU













 955




AUAAAUCC CUGAUGA X GAA AUAUCCUA




UAGGAUAUA GGAUUUAU













 960




ACAUCAUA CUGAUGA X GAA AUCCUAUA




UAUAGGAUU UAUGAUGU













 961




CACAUCAU CUGAUGA X GAA AAUCCUAU




AUAGGAUUU AUGAUGUG













 962




UCACAUCA CUGAUGA X GAA AAAUCCUA




UAGGAUUUA UGAUGUGA













 972




GGGCUCAG CUGAUGA X GAA AUCACAUC




GAUGUGAUU CUGAGCCC













 973




GGGGCUCA CUGAUGA X GAA AAUCACAU




AUGUGAUUC UGAGCCCC













 993




GAUAGCUC CUGAUGA X GAA AUUUCAUG




CAUGAAAUU GAGCUAUC













 999




CCGGCAGA CUGAUGA X GAA AGCUCAAU




AUUGAGCUA UCUGCCGG













1001




CUCCGGCA CUGAUGA X GAA AUAGCUCA




UGAGCUAUC UGCCGGAG













1017




UUUAAGAC CUGAUGA X GAA AGUUUUUC




GAAAAACUU GUCUUAAA













1020




CAAUUUAA CUGAUGA X GAA ACAAGUUU




AAACUUGUC UUAAAUUG













1022




UACAAUUU CUGAUGA X GAA AGACAAGU




ACUUGUCUU AAAUUUGA













1023




GUACAAUU CUGAUGA X GAA AAGACAAG




CUUGUCUUA AAUUGUAC













1027




CGCUGUAC CUGAUGA X GAA AUUUAAGA




UCUUAAAUU GUACCGCG













1030




UCUCGCUG CUGAUGA X GAA ACAAUUUA




UAAAUUGUA CAGCGAGA













1047




CCCACAUU CUGAUGA X GAA AGCUCUGU




ACAGAGCUC AAUGUGGG













1059




GUGAAAUC CUGAUGA X GAA AGCCCCAC




GUGGGGGUU GAUUUCAC













1063




CCAGGUGA CUGAUGA X GAA AUCAAGCC




GGCUUGAUU UCACCUGG













1064




GCCAGGUG CUGAUGA X GAA AAUCAAGC




GCUUGAUUU CACCUGGC













1065




UGCCAGGU CUGAUGA X GAA AAAUCAAG




CUUGAUUUC ACCUGGCA













1076




AAGGUGGA CUGAUGA X GAA AGUGCCAG




CUGGCACUC UCCACCUU













1078




UGAAGGUG CUGAUGA X GAA AGAGUGCC




GGCACUCUC CACCUUCA













1084




AGACUUUG CUGAUGA X GAA AGGUGGAG




CUCCACCUU CAAAGUCU













1085




GAGACUUU CUGAUGA X GAA AAGGUGGA




UCCACCUUC AAAGUCUC













1091




UAUGAUGA CUGAUGA X GAA ACUUUGAA




UUCAAAGUC UCAUCAUA













1093




CUUAUGAU CUGAUGA X GAA AGACUUUG




CAAAGUCUC AUCAUAAG













1096




CUUCUUAU CUGAUGA X GAA AUGAGACU




AGUCUCAUC AUAAGAAG













1099




AAUCUUCU CUGAUGA X GAA AUGAUGAG




CUCAUCAUA AGAAGAUU













1107




CGGUUUAC CUGAUGA X GAA AUCUUCUU




AAGAAGAUU GUAAACCG













1110




UCCCGGUU CUGAUGA X GAA ACAAUCUU




AAGAUUGUA AACCGGGA













1130




UCCCAGGA CUGAUGA X GAA AGGGUUUC




GAAACCCUU UCCUGGGA













1131




GUCCCAGG CUGAUGA X GAA AAGGGUUU




AAACCCUUU CCUGGGAC













1132




AGUCCCAG CUGAUGA X GAA AAAGGGUU




AACCCUUUC CUGGGACU













1154




UGCUCAAA CUGAUGA X GAA ACAUCUUC




GAAGAUGUU UUUGAGCA













1155




GUGCUCAA CUGAUGA X GAA AACAUCUU




AAGAUGUUU UUGAGCAC













1156




GGUGCUCA CUGAUGA X GAA AAACAUCU




AGAUGUUUU UGAGCACC













1157




AGGUGCUC CUGAUGA X GAA AAAACAUC




GAUGUUUUU GAGCACCU













1166




CUAUUGUC CUGAUGA X GAA AGGUGCUC




GAGCACCUU GACAAUAG













1173




ACACUUUC CUGAUGA X GAA AUUGUCAA




UUGAGAAUA GAAAGUGU













1205




CACAGGUG CUGAUGA X GAA AUUCCCCU




AGGGGAAUA CACCUGUG













1215




CUGGACGC CUGAUGA X GAA ACACAGGU




ACCUGUGUA GCGUCCAG













1220




GUCCACUG CUGAUGA X GAA ACGCUACA




UGUAGCGUC CAGUGGAC













1236




UUUCUCUU CUGAUGA X GAA AUCAUCCG




CGGAUGAUC AAGAGAAA













1246




AAAUGUUC CUGAUGA X GAA AUUUCUCU




AGAGAAAUA GAACAUUU













1253




CUCGGACA CUGAUGA X GAA AUGUUCUA




UAGAACAUU UGUCCGAG













1254




ACUCGGAC CUGAUGA X GAA AAUGUUCU




AGAACAUUU GUCCGAGU













1257




UGAACUCG CUGAUGA X GAA ACAAAUGU




ACAUUUGUC CGAGUUCA













1263




UUUGUGUG CUGAUGA X GAA ACUCGGAC




GUCCGAGUU CACACAAA













1264




CUUUGUGU CUGAUGA X GAA AACUCGGA




UCCGAGUUC ACACAAAG













1276




AGCAAUAA CUGAUGA X GAA AGGCUUUG




CAAAGCCUU UUAUUGCU













1277




AAGCAAUA CUGAUGA X GAA AAGGCUUU




AAAGCCUUU UAUUGCUU













1278




AAAGAAAU CUGAUGA X GAA AAAGGCUU




AAGCCUUUU AUUGCUUU













1279




GAAAGCAA CUGAUGA X GAA AAAAGGCU




AGCCUUUUA UUGCUUUC













1281




CCGAAAGC CUGAUGA X GAA AUAAAAGG




CCUUUUAUU GCUUUCGG













1285




ACUACCGA CUGAUGA X GAA AGCAAUAA




UUAUUGCUU UCGGUAGU













1286




CACUACCG CUGAUGA X GAA AAGCAAUA




UAUUGCUUU CGGUAGUG













1287




CCACUACC CUGAUGA X GAA AAAGCAAU




AUUGCUUUC GGGAGUGG













1291




CAUCCCAC CUGAUGA X GAA ACCGAAAG




CUUUCGGUA GUGGGAUG













1304




CCACCAAA CUGAUGA X GAA AUUUCAUC




GAUGAAAUC UUUGGUGG













1306




UUCCACCA CUGAUGA X GAA AGAUUUCA




UGAAAUCUU UGGUGGAA













1307




CUUCCACC CUGAUGA X GAA AAGAUUUC




GAAAUCUUU GGUGGAAG













1330




UCGGACUU CUGAUGA X GAA ACUGCCCA




UGGGCAGUC AAGUCCGA













1335




GGGAUUCG CUGAUGA X GAA ACUUGACU




AGUCAAGUC CGAAUCCC













1341




UUCACAGG CUGAUGA X GAA AUUCGGAC




GUCCGAAUC CCUGUGAA













1352




AACUGAGA CUGAUGA X GAA ACUUCACA




UGUGAAGUA UCUCAGUU













1354




GUAACUGA CUGAUGA X GAA AUACUUCA




UGAAGUAUC UCAGUUAC













1356




GGGUAACU CUGAUGA X GAA AGAUACUU




AAGUAUCUC AGUUACCC













1360




AGCUGGGU CUGAUGA X GAA ACUGAGAU




AUCUCAGUU ACCCAGCU













1361




GAGCUGGG CUGAUGA X GAA AACUGAGA




UCUCAGUUA CCCAGCUC













1369




GAUAUGAG CUGAUGA X GAA AGCUGGGU




ACCCAGCUC CUGAUAUC













1375




CCAUUUGA CUGAUGA X GAA AUCAGGAG




CUCCUGAUA UCAAAUGG













1377




UACCAUUU CUGAUGA X GAA AUAUCAGG




CCUGAUAUC AAAUGGUA













1385




CAUUUCUG CUGAUGA X GAA ACCAUUUG




CAAAUGGUA CAGAAAUG













1404




UUGGACUC CUGAUGA X GAA AUCGGCCU




AGGCCCAUU GAGUCCAA













1409




UGUAGUUG CUGAUGA X GAA ACUCAAUG




CAUUGAGUC CAACUACA













1415




UCAUUGUG CUGAUGA X GAA AGUUGGAC




GUCCAACUA CACAAUGA













1425




UCGCCAAC CUGAUGA X GAA AUCAUUGU




ACAAUGAUU GUUGGCGA













1428




UCAUCGCC CUGAUGA X GAA ACAAUCAU




AUGAUUCUU GGCGAUGA













1440




AUGAUGGU CUGAUGA X GAA AGUUCAUC




GAUGAACUC ACCAUCAU













1446




ACUUCCAU CUGAUGA X GAA AUGGUGAG




CUCACCAUC AUGGAAGU













1478




UGACCGUG CUGAUGA X GAA AGUUUCCU




AGGAAACUA CACGGUCA













1485




GUGAGGAU CUGAUGA X GAA ACCGUGUA




UACACGGUC AUCCUCAC













1488




UUGGUGAG CUGAUGA X GAA AUGACCGU




ACGGUCAUC CUCACCAA













1491




GGGUUGGU CUGAUGA X GAA AGGAUGAC




GUCAUCCUC ACCAACCC













1503




UCCAUUGA CUGAUGA X GAA AUGGGGUU




AACCCCAUU UCAAUGGA













1504




CUCCAUUG CUGAUGA X GAA AAUGGGGU




ACCCCAUUU CAAUGGAG













1505




UCUCCAUU CUGAUGA X GAA AAAUGGGG




CCCCAUUUC AAUGCAGA













1530




ACCAGAGA CUGAUGA X GAA ACCAUGUG




CACAUGGUC UCUCUGGU













1532




CAACCAGA CUGAUGA X GAA AGACCAUG




CAUGGUCUC UCUGGUUG













1534




CACAACCA CUGAUGA X GAA AGAGACCA




UGGUCUCUC UGGUUGUG













1539




ACAUUCAC CUGAUGA X GAA ACCAGAGA




UCUCUGGUU GUGAAUGU













1548




UGGGGUGG CUGAUGA X GAA ACAUUCAC




GUGAAUGUC CCACCCCA













1560




UUCUCACC CUGAUGA X GAA AUCUGGGG




CCCCAGAUC GGUGAGAA













1574




GCGAGAUC CUGAUGA X GAA AGGCUUUC




GAAAGCCUU GAUCUCGC













1578




AUAGGCGA CUGAUGA X GAA AUCAAGGC




GCCUUGAUC UCGCCUAU













1580




CCAUAGGC CUGAUGA X GAA AGAUCAAG




CUUGAUCUC GCCUAUGG













1585




GGAAUCCA CUGAUGA X GAA AGGCGAGA




UCUCGCCUA UGGAUUCC













1591




CUGGUAGG CUGAUGA X GAA AUCCAUAG




CUAUGGAUU CCUACCAG













1592




ACUGGUAG CUGAUGA X GAA AAUCCAUA




UAUGGAUUC CUACCACU













1595




CAUACUGG CUGAUGA X GAA AGGAAUCC




GGAUUCCUA CCAGUAUG













1601




UGGUCCCA CUGAUGA X GAA ACUGGUAG




CUACCAGUA UGGGACCA













1619




UGCAUGUC CUGAUGA X GAA AUGUCUGC




GCAGACAUU GACAUGCA













1632




UUGGCGUA CUGAUGA X GAA ACUGUGCA




UGCACAGUC UACGCCAA













1634




GGUUGGCG CUGAUGA X GAA AGACUGUG




CACAGUCUA CGCCAACC













1645




GUGCAGGG CUGAUGA X GAA AGGGUUGG




CCAACCCUC CCCUGCAC













1659




UACCACUG CUGAUGA X GAA AUGUGGUG




CACCACAUC CAGUGGGA













1667




GCUGCCAG CUGAUGA X GAA ACCACUGG




CCAGUGGUA CUGGCAGC













1677




GCUUCUUC CUGAUGA X GAA AGCUGCCA




UGGCAGCUA GAAGAAGC













1691




GUCUGUAG CUGAUGA X GAA AGCAGGCU




AGCCUGCUC CUACAGAC













1694




CGGGUCUG CUGAUGA X GAA AGGAGCAG




CUGCUCCUA CAGACCCG













1718




UACAAGCA CUGAUGA X GAA ACGGGCUU




AAGCCCGUA UGCUUGUA













1723




UUCUUUAC CUGAUGA X rAA AGCAUACG




CGUAUGCUU GUAAAGAA













1726




CCAUUCUU CUGAUGA X GAA ACAAGCAU




AUGCUUGUA AAGAAUGG













1750




CCCCUGGA CUGAUGA X GAA AUCCUCCA




UGGAGGAUU UCCAGGGG













1751




CCCCCUGG CUGAUGA X GAA AAUCCUCC




GGAGGAUUU CCAGGGGG













1752




CCCCCCUG CUGAUGA X GAA AAAUCCUC




GAGGAUUUC CAGGGGGG













1770




GUGACUUC CUGAUGA X GAA AUCUUGUU




AACAAGAUC GAAGUCAC













1776




UUUUUGGU CUGAUGA X GAA ACUUCGAU




AUCGAAGUC ACCAAAAA













1790




UCAGGGCA CUGAUGA X GAA AUUGGUUU




AAACCAAUA UGCCCUGA













1800




UUUCCUUC CUGAUGA X GAA AUCAGGGC




GCCCUGAUU GAAGGAAA













1821




AGCGUACU CUGAUGA X GAA ACAGUUUU




AAAACUGUA AGUACGCU













1825




GACCAGCG CUGAUGA X GAA ACUUACAG




CUGUAAGUA CGCUGGUC













1833




GCUUGGAU CUGAUGA X GAA ACCAGCGU




ACGCUGGUC AUCCAAGC













1836




GCAGCUUG CUGAUGA X GAA AUGACCAG




CUGGUCAUC CAAGCUGC













1853




ACAACGCU CUGAUGA X GAA ACACGUUG




CAACGUGUC AGCGUUGU













1859




AUUUGUAC CUGAUGA X GAA ACGCUGAC




GUCAGCGUU GUACAAAU













1862




CACAUUUG CUGAUGA X GAA ACAACGCU




AGCGUUGUA CAAAUGUG













1878




GCUUUGUU CUGAUGA X GAA AUGGCUUC




GAAGCCAUC AACAAAGC













1905




AAGGAGAU CUGAUGA X GAA ACCCUCUC




GAGAGGGUC AUCUCCUU













1908




UGGAAGGA CUGAUGA X GAA AUGACCCU




AGGGUCAUC UCCUUCCA













1910




CAUGGAAG CUGAUGA X GAA AGAUGACC




GGUCAUCUC CUUCCAUG













1913




UCACAUGG CUGAUGA X GAA AGGAGAUG




CAUCUCCUU CCAUGUGA













1914




AUCACAUG CUGAUGA X GAA AAGGAGAU




AUCUCCUUC CAUGUGAU













1923




GGACCCCU CUGAUGA X GAA AUCACAUG




CAUGUGAUC AGGGGUCC













1930




AAUUUCAG CUGAUGA X GAA ACCCCUGA




UCAGGGGUC CUGAAAUU













1938




UGCACAGU CUGAUGA X GAA AUUUCAGG




CCUGAAAUU ACUGUGCA













1939




UUGCACAG CUGAUGA X GAA AAUUUCAG




CUGAAAUUA CUGUGCAA













1982




ACAACAGG CUGAUGA X GAA ACACACUC




GAGUGUGUC CCUGUUGU













1988




CAGUGCAC CUGAUGA X GAA ACAGGGAC




GUCCCUGUU GUGCACUG













2008




CUCAAACG CUGAUGA X GAA AUUUCUGU




ACAGAAAUA CGUUUGAG













2012




GGUUCUCA CUGAUGA X GAA ACGUAUUU




AAAUACGUU UGAGAACC













2013




AGGUUCUC CUGAUGA X GAA AACGUAUU




AAUACGUUU GAGAACCU













2022




UACCACGU CUGAUGA X GAA AGGUUCUC




GAGAACCUC ACGUGGUA













2030




CAAGCUUG CUGAUGA X GAA ACCACGUG




CACGUGGUA CAAGCUUG













2037




UGUGAGCC CUGAUGA X GAA AGCUUGUA




UACAAGCUU GGCUCACA













2042




UUGCCUGU CUGAUGA X GAA AGCCAAGC




GCUUGGCUC ACAGGCAA













2054




UGUGGACC CUGAUGA X GAA AUGUUGCC




GGCAACAUC GGUCCACA













2058




CCCAUGUG CUGAUGA X GAA ACCGAUGU




ACAUCGGUC CACAUGGG













2072




GUGUCAGU CUGAUGA X GAA AUUCGCCC




GGGCGAAUC ACUCACAC













2076




ACUGGUGU CUGAUGA X GAA AGUGAUUC




GAAUCACUC ACACCAGU













2085




UUCUUGCA CUGAUGA X GAA ACUGGUGU




ACACCAGUU UGCAAGAA













2086




GUUCUUGC CUGAUGA X GAA AACUGGUG




CACCAGUUU GCAAGAAC













2096




GAGCAUCC CUGAUGA X GAA AGUUCUUG




CAAGAACUU GGAUGCUC













2104




UUUCCAAA CUGAUGA X GAA AGCAUCCA




UGGAUGCUC UUUGGAAA













2106




AGUUUCCA CUGAUGA X GAA AGAGCAUC




GAUGCUCUU UGGAAACU













2107




CAGUUUCC CUGAUGA X GAA AAGAGCAU




AUGCUCUUU GGAAACUG













2129




UGUUAGAA CUGAUGA X GAA ACAUGGUG




CACCAUGUU UUCUAACA













2130




CUGUUAGA CUGAUGA X GAA AACAUGGU




ACCAUGUUU UCUAACAG













2131




GCUGUUAG CUGAUGA X GAA AAACAUGG




CCAUGUUUU CUAACAGC













2132




UGCUGUUA CUGAUGA X GAA AAAACAUG




CAUGUUUUC UAACAGCA













2134




UGUGCUGU CUGAUGA X GAA AGAAAACA




UGUUUUCUA ACAGCACA













2151




ACAAUCAA CUGAUGA X GAA AUGUCAUU




AAUGACAUC UUGAUUGU













2153




CCACAAUC CUGAUGA X GAA AGAUGUCA




UGACAUCUU GAUUGUGG













2157




AAUGCCAC CUGAUGA X GAA AUCAAGAU




AUCUUGAUU GUGGCAUU













2165




CAUUCUGA CUGAUGA X GAA AUGCCACA




UGUGGCAUU UCAGAAUG













2166




GCAUUCUG CUGAUGA X GAA AAUGCCAC




GUGGCAUUU CAGAAUGC













2167




GGCAUUCU CUGAUGA X GAA AAAUGCCA




UGGCAUUUC AGAAUGCC













2177




CCUGCAGA CUGAUGA X GAA AGGCAUUC




GAAUGCCUC UCUGCAGG













2179




GUCCUGCA CUGAUGA X GAA AGAGGCAU




AUGCCUCUC UGCAGGAC













2198




AGCAAACA CUGAUGA X GAA AGUCGCCU




AGGGGACUA UGUUUGCU













2202




GCAGAGCA CUGAUGA X GAA ACAUAGUC




GACUAUGUU UGCUCUGC













2203




AGCAGAGC CUGAUGA X GAA AACAUAGU




ACUAUGUUU GCUCUGCU













2207




CUUGAGCA CUGAUGA X GAA AGCAAACA




UGUUUGCUC UGCUCAAG













2212




CUUAUCUU CUGAUGA X GAA AGCAGAGC




GCUCUGCUC AAGAUAAG













2218




GGUCUUCU CUGAUGA X GAA AUCUUGAG




CUCAAGAUA AGAAGACC













2239




GACCAGGC CUGAUGA X GAA AUGUCUUU




AAAGACAUU GCCUGGUC













2247




AGCUGUUU CUGAUGA X GAA ACCAGGCA




UGCCUGGUC AAACAGCU













2256




AGGAUGAU CUGAUGA X GAA AGCUGUUU




AAACAGCUC AUCAUCCU













2259




UCUAGGAU CUGAUGA X GAA AUGAGCUG




CAGCUCAUC AUCCUAGA













2262




CGCUCUAG CUGAUGA X GAA AUGAUGAG




CUCAUCAUC CUAGAGCG













2265




AUGCGCUC CUGAUGA X GAA AGGAUGAU




AUCAUCCUA GAGCGCAU













2286




UUUCCGGU CUGAUGA X GAA AUCAUGGG




CCCAUGAUC ACCGGAAA













2296




AUUCUCCA CUGAUGA X GAA AUUUCCGG




CCGGAAAUC UGGAGAAU













2305




UGUUGUCU CUGAUGA X GAA AUUCUCCA




UGGAGAAUC AGACAACA













2319




GUCUCGCC CUGAUGA X GAA AUGGUUGU




ACAACCAUU GGCGAGAC













2331




GUCACUUC CUGAUGA X GAA AUGGUCUC




GAGACCAUU GAAGUGAC













2341




UGCUGGGC CUGAUGA X GAA AGUCACUU




AAGUGACUU GCCCAGCA













2351




GAUUUCCA CUGAUGA X GAA AUGCUGGG




CCCAGCAUC UGCAAAUC













2359




UGGGGUAG CUGAUGA X GAA AUUUCCAG




CUGCAAAUC CUACCCCA













2362




GUGUGGGG CUGAUGA X GAA AGGAUUUC




GAAAUCCUA CCCCACAC













2373




AACCAUGU CUGAUGA X GAA AUGUGUGG




CCACACAUU ACAUGGUU













2374




GAACCAUG CUGAUGA X GAA AAUGUGUG




CACACAUUA CAUGGUUC













2381




UGUCUUUG CUGAUGA X GAA ACCAUGUA




UACAUGGUU CAAAGACA













2382




UUGUCUUU CUGAUGA X GAA AACCAUGU




ACAUGGUUC AAAGACAA













2403




GAAUCUUC CUGAUGA X GAA ACCAGGGU




ACCCUGGUA GAAGAUUC













2410




AAUGCCUG CUGAUGA X GAA AUCUUCUA




UAGAAGAUU CAGGCAUU













2411




CAAUGCCU CUGAUGA X GAA AAUCUUCU




AGAAGAUUC AGGCAUUG













2418




CUCAGUAC CUGAUGA X GAA AUGCCUGA




UCAGGCAUU GUACUGAG













2421




UCUCUCAG CUGAUGA X GAA ACAAUGCC




GGCAUUGUA CUGAGAGA













2449




CCUGCGGA CUGAUGA X GAA AGUCAGAU




ACCUGACUA UCCGCAGG













2451




ACCCUGCG CUGAUGA X GAA AUAGUCAG




CUGACUAUC CGCAGGGU













2481




CAGGUGUA CUGAUGA X GAA AGGCCUCC




GGAGGCCUC UACACCUG













2483




GGCAGGUG CUGAUGA X GAA AGAGGCCU




AGGCCUCUA CACCUGCC













2505




CAGCCAAG CUGAUGA X GAA ACAUUGCA




UGCAAUGUC CUUGGCUG













2508




GCACAGCC CUGAUGA X GAA AGGACAUU




AAUGUCCUU GGCUGUGC













2532




AUUAUGAA CUGAUGA X GAA AGCGUCUC




GAGACGCUC UUCAUAAU













2534




CUAUUAUG CUGAUGA X GAA AGAGCGUC




GACGCUCUU CAUAAUAG













2535




UCUAUUAU CUGAUGA X GAA AAGAGCGU




ACGCUCUUC AUAAUAGA













2538




CCUUCUAU CUGAUGA X GAA AUGAAGAG




CUCUUCAUA AUAGAAGG













2541




GCACCUUC CUGAUGA X GAA AUUAUGAA




UUCAUAAUA GAAGGUGC













2567




UGACUUCC CUGAUGA X GAA AGUUGGUC




GACCAACUU GGAAGUCA













2574




AGGAUAAU CUGAUGA X GAA ACUUCCAA




UUGGAAGUC AUUAUCCU













2577




ACGAGGAU CUGAUGA X GAA AUGACUUC




GAAGUCAUU AUCCUCGU













2578




GACGAGGA CUGAUGA X GAA AAUGACUU




AAGUCAUUA UCCUCGUC













2580




CCGACGAG CUGAUGA X GAA AUAAUGAC




GUCAUUAUC CUCGUCGG













2583




GUGCCGAC CUGAUGA X GAA AGGAUAAU




AUUAUCCUC GUCGGCAC













2586




GCAGUGCC CUGAUGA X GAA ACGAGGAU




AUCCUCGUC GGCACUGC













2601




AACAUGGC CUGAUGA X GAA AUCACUGC




GCAGUGAUU GCCAUGUU













2609




GCCAGAAG CUGAUGA X GAA ACAUGGCA




UGCCAUGUU CUUCUGGC













2610




AGCCAGAA CUGAUGA X GAA AACAUGGC




GCCAUGUUC UUCUGGCU













2612




GGAGCCAG CUGAUGA X GAA AGAACAUG




CAUGUUCUU CUGGCUCC













2613




AGGAGCCA CUGAUGA X GAA AAGAACAU




AUGUUCUUC UGGCUCCU













2619




ACAAGAAG CUGAUGA X GAA AGCCAGAA




UUCUGGCUC CUUCUUGU













2622




AUGAGAAG CUGAUGA X GAA AGGAGCCA




UGGCUCCUU CUUGUCAU













2623




AAUGACAA CUGAUGA X GAA AAGGAGCC




GGCUCCUUC UUGUCAUU













2625




ACAAUGAC CUGAUGA X GAA AGAAGGAG




CUCCUUCUU GUCAUUGU













2628




AGGACAAU CUGAUGA X GAA ACAAGAAG




CUUCUUGUC AUUGUCCU













2631




CGUAGGAG CUGAUGA X GAA AUGACAAG




CUUGUCAUU GUCCUACG













2634




GUCCGUAG CUGAUGA X GAA ACAAUGAC




GUCAUUGUC CUACGGAC













2637




ACGGUCCG CUGAUGA X GAA AGGACAAU




AUUGUCCUA CGGACCGU













2646




GCCCGCUU CUGAUGA X GAA ACGGUCCG




CGGACCGUU AAGCGGGC













2647




GGCCCGCU CUGAUGA X GAA AACGGUCC




GGACCGUUA AGCGGGCC













2681




UAGACAAG CUGAUGA X GAA AGCCUGUC




GACAGGCUA CUUGUCUA













2684




CAAUAGAC CUGAUGA X GAA AGUAGCCU




AGGCUACUU GUCUAUUG













2687




UGACAAUA CUGAUGA X GAA ACAAGUAG




CUACUUGUC UAUUGUCA













2689




CAUGACAA CUGAUGA X CAA AGACAAGU




ACUUGUCUA UUGUCAUG













2691




UCCAUGAC CUGAUGA X GAA AUAGACAA




UUGUCUAUU GUCAUGGA













2694




GGAUCCAU CUGAUGA X GAA ACAAUAGA




UCUAUUGUC AUGGAUCC













2701




UUCAUCUG CUGAUGA X GAA AUCCAUGA




UCAUGGAUC CAGAUGAA













2711




CCAAGGGC CUGAUGA X GAA AUUCAUCU




AGAUGAAUU GCCCUUGG













2717




GCUCAUCC CUGAUGA X GAA AGGGCAAU




AUUGCCCUU GGAUGAGC













2738




CAUAAGGC CUGAUGA X GAA AGCGUUCA




UGAACGCUU GCCUUAUG













2743




GGCAUCAU CUGAUGA X GAA AGGCAAGC




GCUUGCCUU AUGAUGCC













2744




UGGCAUCA CUGAUGA X GAA AAGGCAAG




CUUGCCUUA UGAUGCCA













2765




CCCUGGGG CUGAUGA X GAA AUUCCCAC




GUGGGAAUU CCCCAGGG













2766




UCCCUCGG CUGAUGA X GAA AAUUCCCA




UCGGAAUUC CCCAGGGA













2787




GGUUUUCC CUGAUGA X GAA AGUUUCAG




CUGAAACUA GGAAAACC













2797




GCGGCCAA CUGAUGA X GAA AGGUUUUC




GAAAACCUC UUGGCCGC













2799




CCGCGGCC CUGAUGA X GAA AGAGGGUU




AAACCUCUU GGCCGCGG













2813




CUUGGCCG CUGAUGA X GAA AGGCACCG




CGGUGCCUU CGGCCAAG













2814




ACUUGGCC CUGAUGA X GAA AAGGCACC




GGUGCCUUC GGCCAAGU













2826




UCUGCCUC CUGAUGA X GAA AUCACUUG




CAAGUGAUU GAGGCAGA













2839




AAUUCCAA CUGAUGA X GAA AGCGUCUG




CAGACGCUU UUGGAAUU













2840




CAAUUCCA CUGAUGA X GAA AAGCGUCU




AGACGCUUU UGGAAUUG













2841




UCAAUUCC CUGAUGA X GAA AAAGCGUC




GACGCUUUU GGAAUUGA













2847




GUCUUGUC CUGAUGA X GAA AUUCCAAA




UUUGGAAUU GACAAGAC













2863




UGUUUUGC CUGAUGA X GAA AGUCGCUG




CAGCGACUU GCAAAACA













2874




UUGACGGC CUGAUGA X GAA ACUGUUUU




AAAACAGUA GCCGUCAA













2880




AACAUCUU CUGAUGA X GAA ACGGCUAC




GUAGCCGUC AAGAUGUU













2888




CUUCUUUC CUGAUGA X GAA ACAUCUUG




CAACAUGUU GAAAGAAG













2917




GAGGGCUC CUGAUGA X GAA AUGCUCGC




GCGAGCAUC GAGCCCUC













2925




UCAGACAU CUGAUGA X GAA AGGGCUCG




CGAGCCCUC AUGUCUGA













2930




UGAGUUCA CUGAUGA X GAA ACAUGAGG




CCUCAUGUC UGAACUCA













2937




AGGAUCUU CUGAUGA X GAA AGUUCAGA




UCUGAACUC AAGAUCCU













2943




UGGAUGAG CUGAUGA X GAA AUCUUGAG




CUCAAGAUC CUCAUCCA













2946




AUGUGGAU CUGAUGA X GAA AGGAUCUU




AAGAUCCUC AUCCACAU













2949




CCAAUGUG CUGAUGA X GAA AUGAGGAU




AUCCUCAUC CACAUUGG













2955




UGGUGACC CUGAUGA X GAA AUGUGGAU




AUCCACAUU GGUCACCA













2959




GAGAUGGU CUGAUGA X GAA ACCAAUGU




ACAUUGGUC ACCAUCUC













2965




CACAUUGA CUGAUGA X GAA AUGGUGAC




GUCACCAUC UCAAUGUG













2967




ACCACAUU CUGAUGA X GAA AGAUGGUG




CACCAUCUC AAUGUGUU













2982




GCGCCUAG CUGAUGA X GAA AGGUUCAC




GUGAACCUC CUAGGCGC













2985




CAGGCGCC CUGAUGA X GAA AGGAGGUU




AACCUCCUA GGCGCCUG













3013




CACCAUGA CUGAUGA X GAA AGGCCCUC




GAGGGCCUC UCAUGGUG













3015




AUCACCAU CUGAUGA X GAA AGAGGCCC




GGGCCUCUC AUGGUGAU













3024




AAUUCCAC CUGAUGA X GAA AUCACCAU




AUGGUGAUU GUGGAAUU













3032




ACUUGCAG CUGAUGA X GAA AUUCCACA




UGUGGAAUU CUGCAAGU













3033




AACUUGCA CUGAUGA X GAA AAUUCCAC




GUGGAAUUC UGCAAGUU













3041




CGUUUCCA CUGAUGA X GAA ACUUGCAG




CUGGAAGUU UGGAAACC













3042




ACGUUUCC CUGAUGA X GAA AACUUGCA




UGCAAGUUU GGAAACCU













3051




UAAGUUGA CUGAUGA X GAA AGGUUUCC




GGAAACCUA UCAACUUA













3053




AGUAAGUU CUGAUGA X GAA AUAGGUUU




AAACCUAUC AACUUACU













3058




CCGUAAGU CUGAUGA X GAA AGUUGAUA




UAUCAACUU ACUUACGG













3059




CCCGUAAG CUGAUGA X GAA AAGUUGAU




AUCAACUUA CUUACGGG













3062




UGCCCCGU CUGAUGA X GAA AAUAAGUU




AACUUACUU ACGGGGCA













3063




UUGCCCCG CUGAUGA X GAA AAGUAAGU




ACUUACUUA CGGGGCAA













3083




AGGGAACA CUGAUGA X GAA AUUCAUUU




AAAUGAAUU UGUUCCCU













3084




UAGGGAAC CUGAUGA X GAA AAUUCAUU




AAUGAAUUU GUUCCCUA













3087




UUAUAGGG CUGAUGA X GAA ACAAAUUC




GAAUUUGUU CCCUAUAA













3088




CUUAUAGG CUGAUGA X GAA AACAAAUU




AAUUUGUUC CCUAUAAG













3092




UGCUCUUA CUGAUGA X GAA AGGGAACA




UGUUCCCUA UAAGAGCA













3094




UUUGCUCU CUGAUGA X GAA AUAGGGAA




UUCCCUAUA AGAGCAAA













3113




CCUGGCGG CUGAUGA X GAA AGCGUGCC




GGCACGCUU CCGCCAGG













3114




CCCUGGCG CUGAUGA X GAA AAGCGUGC




GCACGCUUC CGCCAGGG













3131




CCCCAACG CUGAUGA X GAA AGUCCUUG




CAAGGACUA CGUUGGGG













3135




AGCUCCCC CUGAUGA X GAA ACGUAGUC




GACUACGUU GGGGAGCU













3144




UCCACGGA CUGAUGA X GAA AGCUCCCC




GGGGAGCUC UCCGUGGA













3146




GAUCCACG CUGAUGA X GAA AGAGCUCC




GGAGCUCUC CGUGGAUC













3154




UCUUUUCA CUGAUGA X GAA AUCCACGG




CCGUGGAUC UGAAAAGA













3167




UGCUGUCC CUGAUGA X GAA AGCGUCUU




AAGACGCUU GGACAGCA













3177




CUGCUGGU CUGAUGA X GAA AUGCUGUC




GACAGCAUC ACCACCAG













3194




AGCUGGCA CUGAUGA X GAA AGCUCUGG




CCAGAGCUC UGCCAGCU













3203




CAAAGCCU CUGAUGA X GAA AGCUGGCA




UGCCAGCUC AGGCUUUG













3209




CCUCAACA CUGAUGA X GAA AGCCUGAG




CUCAGGCUU UGUUGAGG













3210




UCCUCAAC CUGAUGA X GAA AAGCCUGA




UCAGGCUUU GUUGAGGA













3213




UUCUCCUC CUGAUGA X GAA ACAAAGCC




GGCUUUGUU GAGGAGAA













3224




CACUGAGC CUGAUGA X GAA AUUUCUCC




GGAGAAAUC GCUCAGUG













3228




ACAUCACU CUGAUGA X GAA AGCGAUUU




AAAUCGCUC AGUGAUGU













3237




UCUUCCUC CUGAUGA X GAA ACAUCACU




AGUGAUGUA GAGGAAGA













3253




UUCUUCAG CUGAUGA X GAA AGCUUCUU




AAGAAGCUU CUGAAGAA













3254




GUUCUUCA CUGAUGA X GAA AAGCUUCU




AGAAGCUUC UGAAGAAC













3266




AGUCCUUG CUGAUGA X GAA ACAGUUCU




AGAACUGUA CAAGGACU













3275




AGGUCAGG CUGAUGA X GAA AGUCCUUG




CAAGGACUU CCUGACCU













3276




AAGGUCAG CUGAUGA X GAA AAGUCCUU




AAGGACUUC CUGACCUU













3284




GAUGCUCC CUGAUGA X GAA AGGUCAGG




CCUGACCUU GGAGCAUC













3292




ACAGAUGA CUGAUGA X GAA AUGCUCCA




UGGAGCAUC UCAUCUGU













3294




UAACAGAU CUGAUGA X GAA AGAUGCUC




GAGCAUCUC AUCUGUUA













3297




CUGUAACA CUGAUGA X GAA AUGAGAUG




CAUCUCAUC UGUUACAG













3301




GAAGCUGU CUGAUGA X GAA ACAGAUGA




UCAUCUGUU ACAGCUUC













3302




GGAAGCUG CUGAUGA X GAA AACAGAUG




CAUCUGUUA CAGCUUCC













3308




CCACUUGG CUGAUGA X GAA AGCUGUAA




UUACAGCUU CCAAGUGG













3309




GCCACUUG CUGAUGA X GAA AAGCUGUA




UACAGCUUC CAAGUGGC













3319




CAUGCCCU CUGAUGA X GAA AGCCACUU




AAGUGGCUA AGGGCAUG













3332




AUGCCAAG CUGAUGA X GAA ACUCCAUG




CAUGGAGUU CUUGGCAU













3333




GAUGCCAA CUGAUGA X GAA AACUCCAU




AUGGAGUUC UUGGCAUC













3335




UUGAUGCC CUGAUGA X GAA AGAACUCC




GGAGUUCUU GGCAUCAA













3341




ACUUCCUU CUGAUGA X GAA AUGCCAAG




CUUGGCAUC AAGGAAGU













3352




CCUGUGGA CUGAUGA X GAA ACACUUCC




GGAAGUGGA UCCACAGG













3354




UCCCUGUG CUGAUGA X GAA AUACACUU




AAGUGUAUC CACAGGGA













3381




GAUAGGAG CUGAUGA X GAA AUGUUUCG




CGAAACAUU CUCCUAUC













3382




CGAUAGGA CUGAUGA X GAA AAUGUUUC




GAAACAUUC UCCUAUCG













3384




UCCGAUAG CUGAUGA X GAA AGAAUGUU




AACAUUCUC CUAUCGGA













3387




UUCUCCGA CUGAUGA X GAA AGGAGAAU




AUUCUCCUA UCGGAGAA













3389




UCUUCUCC CUGAUGA X GAA AUAGGAGA




UCUCCUAUC GGAGAAGA













3405




CAGAUCUU CUGAUGA X GAA ACCACAUU




AAUGUGGUU AAGAUCUG













3406




ACAGAUCU CUGAUGA X GAA AACCACAU




AUGUGGJUA AGAUCUGU













3411




AAGUCACA CUGAUGA X GAA AUCUUAAC




GUUAAGAUC UGUGACUU













3419




CCAAGCCG CUGAUGA X GAA AGUCACAG




GUGUGACUU CGGCUUGG













3420




GCCAAGCC CUGAUGA X GAA AAGUCACA




UGUGACUUC GGCUUGGC













3425




CCCGGGCC CUGAUGA X GAA AGCCGAAG




CUUCGGCUU GGCCCGGG













3438




UCUUUAUA CUGAUGA X GAA AUGUCCCG




CGGGACAUU UAUAAAGA













3439




GUCUUUAU CUGAUGA X GAA AAUGUCCC




GGGACAUUU AUAAAGAC













3440




GGUCUUUA CUGAUGA X GAA AAAUGUCC




GGACAUUUA UAAAGACC













3442




CGGGUCUU CUGAUGA X GAA AUAAAUGU




ACAUUUAUA AAGACCCG













3454




UCUGACAU CUGAUGA X GAA AUCCGGGU




ACCCGGAUU AUGUCAGA













3455




UUCUGACA CUGAUGA X GAA AAUCCGGG




CCCGGAUUA UGUCAGAA













3459




CCUUUUCU CUGAUGA X GAA ACAUAAUC




GAUUAUGUC AGAAAAGG













3480




UUCAAAGG CUGAUGA X GAA AGUCGGGC




GCCCGACUC CCUUUGAA













3484




CCACUUCA CUGAUGA X GAA AGGGAGUC




GACUCCCUU UGAAGUGG













3485




UCCACUUC CUGAUGA X GAA AAGGGAGU




ACUCCCUUU GAAGUGGA













3510




CUGUCAAA CUGAUGA X GAA AUGGUUUC




CAAACCAUU UUUGACAG













3511




UCUGUCAA CUGAUGA X GAA AAUGGUUU




AAACCAUUU UUGACAGA













3512




CUCUGUCA CUGAUGA X GAA AAAUGGUU




AACCAUUUU UGACAGAG













3513




ACUCUGUC CUGAUGA X GAA AAAAUGGU




ACCAUUUUU GACAGAGU













3522




AUUGUGUA CUGAUGA X GAA ACUCUGUC




GACAGAGUA UACACAAU













3524




GAAUUGUG CUGAUGA X GAA AUACUCUG




CAGAGUAUA CACAAUUC













3531




UCGCUCUG CUGAUGA X GAA AUUGUGUA




UACACAAUU CAGAGCGA













3532




AUCGCUCU CUGAUGA X GAA AAUUGUGU




ACACAAUUC AGAGCGAU













3548




CACCGAAA CUGAUGA X GAA ACCACACA




UGUGUGGUC UUUCGGUG













3550




CACACCGA CUGAUGA X GAA AGACCACA




UGUGGUCUU UCGGUGUG













3551




ACACACCG CUGAUGA X GAA AAGACCAC




GUGGUCUUU CGGUGUGU













3552




AACACACC CUGAUGA X GAA AAAGACCA




UGGUCUUUC GGUGUGUU













3560




CCCAGAGC CUGAUGA X GAA ACACACCG




CGGUGUGUU GCUCUGGG













3564




AUUUCCCA CUGAUGA X GAA AGCCACAC




GUGUUGCUC UGGGAAAU













3573




AAGGAAAA CUGAUGA X GAA AUUUCCCA




UGGGAAAUA UUUUCCUU













3575




CUAAGGAA CUGAUGA X GAA AUAUUUCC




GGAAAUAUU UUCCUUAG













3576




CCUAAGGA CUGAUGA X GAA AAUAUUUC




GAAAUAUUU UCCUUAGG













3577




ACCUAAGG CUGAUGA X GAA AAAUAUUU




AAAUAUUUU CCUUAGGU













3578




CACCUAAG CUGAUGA X GAA AAAAUAUU




AAUAUUUUC CUUAGGUG













3581




AGGCACCU CUGAUGA X GAA AGGAAAAU




AUUUUCCUU AGGUGCCU













3582




GAGGCACC CUGAUGA X GAA AAGGAAAA




UUUUCCUUA GGUGCCUC













3590




GGUAUGGG CUGAUGA X GAA AGGCACCU




AGGUGCCUC CCCAUACC













3596




CCCCAGGG CUGAUGA X GAA AUGGGGAG




CUCCCCAUA CCCUGGGG













3606




UGAAUCUU CUGAUGA X GAA ACCCCAGG




CCUGGGGUC AAGAUUGA













3612




UCUUCAUC CUGAUGA X GAA AUCUUGAC




GUCAAGAUU GAUGAAGA













3623




UCCUACAA CUGAUGA X GAA AUUCUUCA




UGAAGAAUU UUGUAGGA













3624




CUCCUACA CUGAUGA X GAA AAUUCUUC




GAAGAAUUU UGUAGGAG













3625




UCUCCUAC CUGAUGA X GAA AAAUUCUU




AAGAAUUUU GUAGGAGA













3628




CAAUCUCC CUGAUGA X GAA ACAAAAUU




AAUUUUGUA GGAGAUUG













3635




CUUCUUUC CUGAUGA X GAA AUCUCCUA




UAGGAGAUU GAAAGAAG













3649




CCGCAUUC CUGAUGA X GAA AGUUCCUU




AAGGAACUA GAAUGCGG













3661




GUAGUCAG CUGAUGA X GAA AGCCCGCA




UGCGGGCUC CUGACUAC













3668




GGGUAGUG CUGAUGA X GAA AGUCAGGA




UCCUGACUA CACUACCC













3673




UUCUGGGG CUGAUGA X GAA AGUGUAGU




ACUACACUA CCCCACAA













3686




UGGUCUGG CUGAUGA X GAA ACAUUUCU




AGAAAUGUA CCAGACCA













3734




CUGAAAAC CUGAUGA X GAA AGGGUCUC




GAGACCCUC GUUUUCAG













3737




ACUCUGAA CUGAUGA X GAA ACGAGGGU




ACCCUCGUU UUCAGAGU













3738




AACUCUGA CUGAUGA X GAA AACGAGGG




CCCUCGUUU UCAGAGUU













3739




CAACUCUG CUGAUGA X GAA AAACGAGG




CCUCGUUUU CAGAGUUG













3740




CCAACUCU CUGAUGA X GAA AAAACGAG




CUCGUUUUC AGAGUUGG













3746




GCUCCACC CUGAUGA X GAA ACUCUGAA




UUCAGAGUU GGUGGAGC













3757




GUUUCCCA CUGAUGA X GAA AUGCUCCA




UGGAGCAUU UGGGAAAC













3758




GGUUUCCC CUGAUGA X GAA AAUGCUCC




GGAGCAUUU GGGAAACC













3768




GCUUGCAG CUGAUGA X GAA AGCUUUUC




GGAAACCUC CUGCAAGC













3803




GAACAAUA CUGAUGA X GAA AGUCUUUG




CAAAGACUA UAUUGUUC













3805




AAGAACAA CUGAUGA X GAA AUAGUCUU




AAGACUAUA UUGUUCUU













3807




GGAAGAAC CUGAUGA X GAA AUAUAGUC




GACUAUAUU GUUCUUCC













3810




AUUGGAAG CUGAUGA X GAA ACAAUAUA




UAUAUUGUU CUUCCAAU













3811




CAUUGGAA CUGAUGA X GAA AACAAUAU




AUAUUGUUC UUCCAAUG













3813




GACAUUGG CUGAUGA X GAA AGAACAAU




AUUGUUCUU CCAAUGUC













3814




UGACAUUG CUGAUGA X GAA AAGAACAA




UUGUUCUUC CAAUGUCA













3821




GUGUCUCU CUGAUGA X GAA ACAUUGGA




UCCAAUGUC AGAGACAC













3847




GAGUCCAG CUGAUGA X GAA AUCCUCUU




AAGAGGAUU CUGGACUC













3848




AGAGUCCA CUGAUGA X GAA AAUCCUCU




AGAGGAUUC UGGACUCU













3855




GGCAGGGA CUGAUGA X GAA AGUCCAGA




UCUGGACUC UCCCUGCC













3857




UAGGCAGG CUGAUGA X GAA AGAGUCCA




UGGACUCUC CCUGCCUA













3865




AGGUGAGG CUGAUGA X GAA AGGCAGGG




CCCUGCCUA CCUCACCU













3869




AAACAGGU CUGAUGA X GAA AGGUAGGC




GCCUACCUC ACCUGUUU













3876




AUACAGGA CUGAUGA X GAA ACAGGUGA




UCACCUGUU UCCUGUAU













3877




CAUACAGG CUGAUGA X GAA AACAGGUG




CACCUGUUU CCUGUAUG













3878




CCAUACAG CUGAUGA X GAA AAACAGGU




ACCUGUUUC CUGUAUGG













3883




UUCCUCCA CUGAUGA X GAA ACAGGAAA




UUUCCUGUA UGGAGGAA













3914




CAUAAUGG CUGAUGA X GAA AUUUGGGG




CCCCAAAUU CCAUUAUG













3915




UCAUAAUG CUGAUGA X GAA AAUUUGGG




CCCAAAUUC CAUUAUGA













3919




GUUGUCAU CUGAUGA X GAA AUGGAAUU




AAUUCCAUU AUGACAAC













3920




UGUUGUCA CUGAUGA X GAA AAUGGAAU




AUUCCAUUA UGACAACA













3939




UAAUGACU CUGAUGA X GAA AUUCCUGC




GCAGGAAUC AGUCAUUA













3943




GAGAUAAU CUGAUGA X GAA ACUGAUUC




GAAUCAGUC AUUAUCUC













3946




CUGGAGAU CUGAUGA X GAA AUGACUGA




UCAGUCAUU AUCUCCAG













3947




UCUGGAGA CUGAUGA X GAA AAUGACUG




CAGUCAUUA UCUCCAGA













3949




GUUCUGGA CUGAUGA X GAA AUAAUGAC




GUCAUUAUC UCCAGAAC













3951




CUGUUCUG CUGAUGA X GAA AGAUAAUG




CAUUAUCUC CAGAACAG













3961




CUUUCGCU CUGAUGA X GAA ACUGUUCU




AGAACAGUA AGCGAAAG













3987




AAUGUUUU CUGAUGA X GAA ACACUCAC




GUGAGUGUA AAAACAUU













3995




UAUCUUCA CUGAUGA X GAA AUGUUUUU




AAAAACAUU UGAAGAUA













3996




AUAUCUUC CUGAUGA X GAA AAUGUUUU




AAAACAUUU GAAGAUAU













4003




CAAUGGGA CUGAUGA X GAA AUCUUCAA




UUGAAGAUA UCCCAUUG













4005




UCCAAUGG CUGAUGA X GAA AUAUCUUC




GAAGAUAUC CCAUUGGA













4010




GUUCCUCC CUGAUGA X GAA AUGGGAUA




UAUCCCAUU GGAGGAAC













4026




AUCACUUU CUGAUGA X GAA ACUUCUGG




CCAGAAGUA AAAGUGAU













4035




UCAUCUGG CUGAUGA X GAA AUCACUUU




AAAGUGAUC CCAGAUGA













4068




GAUGCAAG CUGAUGA X GAA ACCAUCCC




GGGAUGGUC CUUGCAUC













4071




UCUGAUGC CUGAUGA X GAA AGGACCAU




AUGGUCCUU GCAUCAGA













4076




GCUCUUCU CUGAUGA X GAA AUGCAAGG




CCUUGCAUC AGAAGAGC













4093




GUCUUCCA CUGAUGA X GAA AGUUUUCA




UGAAAACUC UGGAAGAC













4112




AUGGAGAU CUGAUGA X GAA AUUUGUUC




GAACAAAUU AUCUCCAU













4113




GAUGGAGA CUGAUGA X GAA AAUUUGUU




AACAAAUUA UCUCCAUC













4115




AAGAUGGA CUGAUGA X GAA AUAAUUUG




CAAAUUAUC UCCAUCUU













4117




AAAAGAUG CUGAUGA X GAA AGAUAAUU




AAUUAUCUC CAUCUUUU













4121




CACGAAAA CUGAUGA X GAA AUGGAGAU




AUCUCCAUC UUUUGGUG













4123




UCCACCAA CUGAUGA X GAA AGAUGGAG




CUCCAUCUU UUGGUGGA













4124




UUCCACCA CUGAUGA X GAA AAGAUGGA




UCCAUCUUU UGGUGGAA













4125




AUUCCACC CUGAUGA X GAA AAAGAUGG




CCAUCUUUU GGUGGAAU













4144




CCUGCUUU CUGAUGA X GAA ACUGGGCA




UGCCCAGUA AAAGCAGG













4157




AGGCCACA CUGAUGA X GAA ACUCCCUG




CAGGGAGUC UGUGGCCU













4166




AGCCUUCC CUGAUGA X GAA AGGCCACA




UGUCGCCUC GGAAGGCU













4175




UCUGCUUG CUGAUGA X GAA AGCCUUCC




GGAAGGCUC CAACCAGA













4193




CAGACUGG CUGAUGA X GAA AGCCACUG




CAGUGGCUA CCAGUCUG













4199




GAUACCCA CUGAUGA X GAA ACUGGUAG




CUACCAGUC UGGGUAUC













4205




CUGAGUGA CUGAUGA X GAA ACCCAGAC




GUCUGGGUA UCACUCAG













4207




AUCUGAGU CUGAUGA X GAA AUACCCAG




CUGGGUAUC ACUCAGAU













4211




UGUCAUCU CUGAUGA X GAA AGUGAUAC




GUAUCACUC AGAUGACA













4235




CGCUGGAG CUGAUGA X GAA ACACGGUG




CACCGUGUA CUCCAGCG













4238




CGUCGCUG CUGAUGA X GAA AGUACACG




CGUGUACUC CAGCGACG













4257




AUCUUUAA CUGAUGA X GAA AGUCCUGC




GCAGGACUU UUAAAGAU













4258




CAUCUUUA CUGAUGA X GAA AAGUCCUG




CAGGACUUU UAAAGAUG













4259




CCAUCUUU CUGAUGA X GAA AAAGUCCU




AGGACUUUU AAAGAUGG













4260




ACCAUCUU CUGAUGA X GAA AAAAGUCC




GGACUUUUA AAGAUGGU













4281




UCAGCGUG CUGAUGA X GAA ACUGGAGC




GCUGCAGUU CACGCUGA













4282




GUCAGCGU CUGAUGA X GAA AACUGCAG




CUGCAGUUC ACGCUGAC













4292




UGGUCCCU CUGAUGA X GAA AGUCAGCG




CGCUGACUC AGGGACCA













4311




CAGGAGGU CUGAUGA X GAA AGCUGCAG




CUGCAGCUC ACCUCCUG













4316




UUAAACAG CUGAUGA X CAA AGGUGAGC




GCUCACCUC CUCUUUAA













4321




UCCAUUUA CUGAUGA X GAA ACAGGAGG




CCUCCUGUU UAAAUGGA













4322




UUCCAUUU CUGAUGA X GAA AACAGGAG




CUCCUCUUU AAAUGGAA













4323




CUUCCAUU CUGAUGA X GAA AAACAGGA




UCCUGUUUA AAUGGAAG













4336




CGGGACAG CUGAUGA X GAA ACCACUUC




GAAGUGGUC CUGUCCCG













4341




GGAGCCGG CUGAUGA X GAA ACAGGACC




GGUCCUGUC CCGGCUCC













4348




UGGGGGCG CUGAUGA X GAA AGCCGGGA




UCCCGGCUC CGCCCCCA













4360




AUUUCCAG CUGAUGA X GAA AGUUGGGG




CCCCAACUC CUGGAAAU













4369




UCUCUCGU CUGAUGA X GAA AUUUCCAG




CUGGAAAUC ACGAGAGA













4387




GAAAAUCU CUGAUGA X GAA AGCAGCAC




GUGCUGCUU AGAUUUUC













4388




UGAAAAUC CUGAUGA X GAA AACCAGCA




UGCUGCUUA GAUUUUCA













4392




CACUUGAA CUGAUGA X GAA AUCUAAGC




GCUUAGAUU UUCAAGUG













4393




ACACUUGA CUGAUGA X GAA AAUCUAAG




CUUAGAUUU UCAAGUGU













4394




AACACUUG CUGAUGA X GAA AAAUCUAA




UUAGAUUUU CAAGUGUU













4395




CAACACUU CUGAUGA X GAA AAAAUCUA




UAGAUUUUC AAGUGUUG













4402




GAAAGAAC CUGAUGA X GAA ACACUUGA




UCAAGUGUU GUUCUUUC













4405




GUGGAAAG CUGAUGA X GAA ACAACACU




AGUGUUGUU CUUUCCAC













4406




GGUGGAAA CUGAUGA X GAA AACAACAC




GUGUUGUUC UUUCCACC













4408




GUGGUGGA CUGAUGA X GAA AGAACAAC




GUUGUUCUU UCCACCAC













4409




GGUGGUGG CUGAUGA X GAA AAGAACAA




UUGUUCUUU CCACCACC













4410




GGGUGGUG CUGAUGA X GAA AAAGAACA




UGUUCUUUC CACCACCC













4425




AAUGUGGC CUGAUGA X GAA ACUUCCGG




CCGGAAGUA GCCACAUU













4433




GAAAAUCA CUGAUGA X GAA AUGUGGCU




AGCCACAUU UGAUUUUC













4434




UGAAAAUC CUGAUGA X GAA AAUGUGGC




GCCACAUUU GAUUUUCA













4438




AAAAUGAA CUGAUGA X GAA AUCAAAUG




CAUUUGAUU UUCAUUUU













4439




AAAAAUGA CUGAUGA X GAA AAUCAAAU




AUUUGAUUU UCAUUUUU













4440




CAAAAAUG CUGAUGA X GAA AAAUCAAA




UUUGAUUUU CAUUUUUG













4441




CCAAAAAU CUGAUGA X GAA AAAAUCAA




UUGAUUUUC AUUUUUGG













4444




CCUCCAAA CUGAUGA X GAA AUGAAAAU




AUUUUCAUU UUUGGAGG













4445




UCCUCCAA CUGAUGA X GAA AAUGAAAA




UUUUCAUUU UUGGAGGA













4446




CUCCUCCA CUGAUGA X GAA AAAUGAAA




UUUCAUUUU UGGAGGAG













4447




CCUCCUCC CUGAUGA X GAA AAAAUGAA




UUCAUUUUU GGAGGAGG













4461




UGGAGUCU CUGAUGA X GAA AGGUCCCU




AGGGACCUC AGACUGCA













4477




CUGAGGAC CUGAUGA X GAA AGCUCCUU




AAGGAGCUU GUCCUCAG













4480




GCCCUGAG CUGAUGA X GAA ACAAGCUC




GAGCUUGUC CUCAGGGC













4483




AAUGCCCU CUGAUGA X GAA AGGACAAG




CLUUJCCUC AGGGCAUU













4491




UCUCUGGA CUGAUGA X GAA AUGCCCUG




CAGGGCAUU UCCAGAGA













4492




UUCUCUGG CUGAUGA X GAA AAUGCCCU




AGGGCAUUU CCAGAGAA













4493




CUUCUCUG CUGAUGA X GAA AAAUGCCC




GGGCAUUUC CAGAGAAG













4525




GUAGAGUC CUGAUGA X GAA ACACAUUC




GAAUGUGUU GACUCUAC













4530




AGAGAGUA CUGAUGA X GAA AGUCAACA




UGUUGACUC UACUCUCU













4532




AAAGAGAG CUGAUGA X GAA AGAGUCAA




UUGACUCUA CUCUCUUU













4535




GGAAAAGA CUGAUGA X GAA AGUAGAGU




ACUCUACUC UCUUUUCC













4537




AUGGAAAA CUGAUGA X GAA AGAGUAGA




UCUACUCUC UUUUCCAU













4539




GAAUGGAA CUGAUGA X GAA AGAGAGUA




UACUCUCUU UUCCAUUC













4540




UGAAUGGA CUGAUGA X GAA AAGAGAGU




ACUCUCUUU UCCAUUCA













4541




AUGAAUGG CUGAUGA X GAA AAAGAGAG




CUCUCUUUU CCAUUCAU













4542




AAUGAAUG CUGAUGA X GAA AAAAGAGA




UCUCUUUUC CAUUCAUU













4546




UUUAAAUG CUGAUGA X GAA AUGGAAAA




UUUUCCAUU CAUUUAAA













4547




UUUUAAAU CUGAUGA X GAA AAUGGAAA




UUUCCAUUC AUUUAAAA













4550




GACUUUUA CUGAUGA X GAA AUGAAUGG




CCAUUCAUU UAAAAGUC













4551




GGACUUUU CUGAUGA X GAA AAUGAAUG




CAUUCAUUU AAAAGUCC













4552




AGGACUUU CUGAUGA X GAA AAAUGAAU




AUUCAUUUA AAAGUCCU













4558




UUAUAUAG CUGAUGA X GAA ACUUUUAA




UUAAAAGUC CUAUAUAA













4561




ACAUUAUA CUGAUGA X GAA AGGACUUU




AAAGUCCUA UAUAAUGU













4563




GCACAUUA CUGAUGA X GAA AUAGGACU




AGUCCUAUA UAAUGUGC













4565




GGGCACAU CUGAUGA X GAA AUAUAGGA




UCCUAUAUA AUGUGCCC













4583




GGUAGUGA CUGAUGA X GAA ACCACAGC




GCUGUGGUC UCACUACC













4585




CUGGUAGU CUGAUGA X GAA AGACCACA




UGUGGUCUC ACUACCAG













4589




UUAACUGG CUGAUGA X GAA AGUGAGAC




GUCUCACUA CCAGUUAA













4595




UUUGCUUU CUGAUGA X GAA ACUGGUAG




CUACCAGUU AAAGAAAA













4596




UUUUGCUU CUGAUGA X GAA AACUGGUA




UACCAGUUA AAGCAAAA













4609




GUGUUUGA CUGAUGA X GAA AGUCUUUU




AAAAGACUU UCAAACAC













4610




CGUGUUUG CUGAUGA X GAA AAGUCUUU




AAAGACUUU CAAACACG













4611




ACGUGUUU CUGAUGA X GAA AAAGUCUU




AAGACUUUC AAACACGU













4625




GGAGGACA CUGAUGA X GAA AGUCCACG




CGUGGACUC UGUCCUCC













4629




UCUUGGAG CUGAUGA X GAA ACAGAGUC




GACUCUGUC CUCCAAGA













4632




ACUUCUUG CUGAUGA X GAA AGGACAGA




UCUGUCCUC CAAGAAGU













4654




GUUUCACA CUGAUGA X GAA AGGUGCCG




CGGCACCUC UGUGAAAC













4668




GCCCAUUC CUGAUGA X GAA AUCCAGUU




AACUGGAUC GAAUGGGC













4683




AACACACA CUGAUGA X GAA AGCAUUGC




GCAAUGCUU UGUGUGUU













4684




CAACACAC CUGAUGA X GAA AAGCAUUG




CAAUGCUUU GUGUGUUG













4691




CCAUCCUC CUGAUGA X GAA ACACACAA




UUGUGUGUU GAGGAUGG













4709




GGCCCUGG CUGAUGA X GAA ACAUCUCA




UGAGAUGUC CCAGGGCC













4722




GGUAGACA CUGAUGA X GAA ACUCGGCC




GGCCGAGUC UGUCUACC













4726




CCAAGGUA CUGAUGA X GAA ACAGACUC




GAGUCUGUC UACCUUGG













4728




CUCCAAGG CUGAUGA X GAA AGACAGAC




GUCUGUCUA CCUUGGAG













4732




AAGCCUCC CUGAUGA X GAA AGGUAGAC




GUCUACCUU GGAGGCUU













4740




CCUCCACA CUGAUGA X GAA AGCCUCCA




UGGAGGCUU UGUGGAGG













4741




UCCUCCAC CUGAUGA X GAA AAGCCUCC




GGAGGGUUU GUGGAGGA













4758




UUGGCUCA CUGAUGA X GAA AGCCCGCA




UGCGGGCUA UGAGCGAA













4771




CCACACUU CUGAUGA X GAA ACACUUGG




CCAAGUGUU AAGUGUGG













4772




CCCACACU CUGAUGA X GAA AACACUUG




CAAGUGUUA AGUGUGGG













4811




CUCGGAGC CUGAUGA X GAA ACUUGCGC




GCGCAAGUC GCUCGGAG













4815




GGGUUUCC CUGAUGA X GAA AGCGACUU




AAGUCGCUC GGAGCG













4826




CAGGCUCC CUGAUGA X GAA ACGGCUCU




AGAGCGGUU GGAGCCUG













4844




GCCAGCAC CUGAUGA X GAA AUGCAUCU




AGAUGCAUU GUGCUGGC













4854




CUCCACCA CUGAUGA X GAA AGCCAGCA




UGCUGGCUC UGGUGGAG













4870




CAGGCCAC CUGAUGA X GAA AGCCCACC




GGUGGGCUU GUGGCCUG













4880




CGUUUCCU CUGAUGA X GAA ACAGGCCA




UGGCCUGUC AGGAAACG













4908




CAAAACCA CUGAUGA X GAA ACCCUGCC




GGCAGGGUU UGGUUUUG













4909




CCAAAACC CUGAUGA X GAA AACCCUGC




GCAGGCUUU GGUUUUGG













4913




CCUUCCAA CUGAUGA X GAA ACCAAACC




GGUUUGGUU UUGGAAGG













4914




ACCUUCCA CUGAUGA X GAA AACCAAAC




GUUUGGUUU UGGAAGGU













4915




AACCUUCC CUGAUGA X GAA AAACCAAA




UUUGGGUUU GGAAGGUU













4923




AGCACGCA CUGAUGA X GAA ACCUUCCA




UGGAAGGUU UGCGUGCU













4924




GAGCACGC CUGAUGA X GAA AACCUUCC




GGAAGGUUU GCGUGCUC













4932




ACUGUGAA CUGAUGA X GAA AGCACGCA




UGCGUGCUC UUCACAGU













4934




CGACUGUG CUGAUGA X GAA AGAGCACG




CGUGCUCUU CACAGUCG













4935




CCGACUGU CUGAUGA X GAA AAGAGCAC




GUGCUCUUC ACAGUCGG













4941




UGUAACCC CUGAUGA X GAA ACUGUGAA




UUCACAGUC GGGUUACA













4946




UCGCCUGU CUGAUGA X GAA ACCCGACU




AGUCGGGUU ACAGGCGA













4947




CUCGCCUG CUGAUGA X GAA AACCCGAC




GUCGGGUUA CAGGCGAG













4957




CCACAGGG CUGAUGA X GAA ACUCGCCU




AGGCGAGUU CCCUGUGG













4958




GCCACAGG CUGAUGA X GAA AACUCGCC




GGCGAGUUC CCUGUGGC













4969




GAGUAGGA CUGAUGA X GAA ACGCCACA




UGUGGCGUU UCCUACUC













4970




GGAGUAGG CUGAUGA X GAA AACGCCAC




GUGGCGUUU CCUACUCC













4971




AGGAGUAG CUGAUGA X GAA AAACGCCA




UGGCGUUUC CUACUCCU













4974




AUUAGGAG CUGAUGA X GAA AGGAAACG




CGUUUCCUA CUCCUAAU













4977




CUCAUUAG CUGAUGA X GAA AGUAGGAA




UUCCUACUC CUAAUGAG













4980




ACUCUCAU CUGAUGA X GAA AGGAGUAG




CUACUCCUA AUGAGAGU













4989




CCGGAAGG CUGAUGA X GAA ACUCUCAU




AUGAGAGUU CCUUCCGG













4990




UCCGGAAG CUGAUGA X GAA AACUCUCA




UGAGAGUUC CUUCCGGA













4993




GAGUCCGG CUGAUGA X GAA AGGAACUC




GAGUUCCUU CCGGACUC













4994




AGAGUCCG CUGAUGA X GAA AAGGAACU




AGUUCCUUC CGGACUCU













5001




ACACGUAA CUGAUGA X GAA AGUCCGGA




UCCGGACUC UUACGUGU













5003




AGACACGU CUGAUGA X GAA AGAGUCCG




CGGACUCUU ACGUGUCU













5004




GAGACACG CUGAUGA X GAA AAGAGUCC




GGACUCUUA CGUGUCUC













5010




GGCCAGGA CUGAUGA X GAA ACACGUAA




UUACGUGUC UCCUGGCC













5012




CAGGCCAG CUGAUGA X GAA AGACACGU




ACGUGUCUC CUGGCCUG













5046




GAAGGAGC CUGAUGA X GAA AGCUGCAU




AUGCAGCUU GCUCCUUC













5050




UGAGGAAG CUGAUGA X GAA AGCAAGCU




AGCUUGCUC CUUCCUCA













5053




AGAUGAGG CUGAUGA X GAA AGGAGCAA




UUGCUCCUU CCUCAUCU













5054




GAGAUGAG CUGAUGA X GAA AAGGAGCA




UGCUCCUUC CUCAUCUC













5057




UGAGAGAU CUGAUGA X GAA AGGAAGGA




UCCUUCCUC AUCUCUCA













5060




GCCUGAGA CUGAUGA X GAA AUGAGGAA




UUCCUCAUC UCUCGGGC













5062




CAGCCUGA CUGAUGA X GAA AGAUGAGG




CCUCAUCUC UCAGGCUG













5064




CACAGCCU CUGAUGA X GAA AGAGAUGA




UCAUCUCUC AGGCUGUG













5076




UCUGAAUU CUGAUGA X GAA AGGCACAG




CUGUGCCUU AAUUCAGA













5077




UUCUGAAU CUGAUGA X GAA AAGGCACA




UGUGCCUUA AUUCAAAA













5080




GUGUUCUG CUGAUGA X GAA AUUAAGGC




GCCUUAAUU CAGAACAC













5081




GGUGUUCU CUGAUGA X GAA AAUUAAGG




CCUUAAUUC AGAACACC













5105




CCUCUGCC CUGAUGA X GAA ACGUUCCU




AGGAACGUC GGCAGAGG













5116




CCCGUCAG CUGAUGA X GAA AGCCUCUG




CAGAGGCUC CUGACGGG













5135




GUUCUCAC CUGAUGA X GAA AUUCUUCG




CGAAGAAUU GUGAGAAC













5156




GAAACCCU CUGAUGA X GAA AGUUUCUG




CAGAAACUC AGGGUUUC













5162




CCAGCAGA CUGAUGA X GAA ACCCUGAG




CUCAGGGUU UCUGCUGG













5163




CCCAGCAG CUGAUGA X GAA AACCCUGA




UCAGGGUUU CUGCUGGG













5164




ACCCAGCA CUGAUGA X GAA AAACCCUG




CAGGGUUUC UGCUGGGU













5203




AACCCUCA CUGAUGA X GAA ACCUGCCA




UGGCAGGUC UGAGGGUU













5211




UGACAGAG CUGAUGA X GAA ACCCUCAG




CUGAGGGUU CUCUGUCA













5212




UGGACAGA CUGAUGA X GAA AACCCUCA




UGAGGGUUC UCUGUCAA













5214




ACUGGACA CUGAUGA X GAA AGAACCCU




AGGGUUCUC UGUCAAGU













5218




CGCCACUU CUGAUGA X GAA ACAGAGAA




UUCUCUGUC AAGUGGCG













5229




UGAGCCUU CUGAUGA X GAA ACCGCCAC




GUGGCGGUA AAGGCUCA













5236




ACCAGCCU CUGAUGA X GAA AGCCUUUA




UAAAGGCUC AGGCUGGU













5247




AGAGGAAG CUGAUGA X GAA ACACCAGC




GCUGGUGUU CUUCCUCU













5248




UAGAGGAA CUGAUGA X GAA AACACCAG




CUGGUGUUC UUCCUCUA













5250




GAUAGAGG CUGAUGA X GAA AGAACACC




GGUGUUCUU CCUCUAUC













5251




AGAUAGAG CUGAUGA X GAA AAGAACAC




GUGUUCUUC CUCUAUCU













5254




UGGAGAUA CUGAUGA X GAA AGGAAGAA




UUCUUCCUC UAUCUCCA













5256




AGUGGAGA CUGAUGA X GAA AGAGGAAG




CUUCCUCUA UCUCCACU













5258




GGAGUGGA CUGAUGA X GAA AUAGAGGA




UCCUCUAUC UCCACUCC













5260




CAGGAGUG CUGAUGA X GAA AGAUAGAG




CUCUAUCUC CACUCCUG













5265




CCUGACAG CUGAUGA X GAA AGUGGAGA




UCUCCACUC CUGUCAGG













5270




GGGGGCCU CUGAUGA X GAA ACAGGAGU




ACUCCUGUC AGGCCCCC













5283




AUACUGAG CUGAUGA X GAA ACUUGGGG




CCCCAAGUC CUCAAUAU













5286




AAAAUACU CUGAUGA X GAA AGGACUUG




CAAGUCCUC AGUAUUUU













5290




AGCUAAAA CUGAUGA X GAA ACUGAGGA




UCCUCAGUA UUUUAGCU













5292




AAAGCUAA CUGAUGA X GAA AUACUGAG




CUCAGUAUU UUAGCUUU













5293




CAAAGCUA CUGAUGA X GAA AAUACUGA




UCAGUAUUU UAGCUUUG













5294




ACAAAGCU CUGAUGA X GAA AAAUACUG




CAGUAUUUU AGCUUUGU













5295




CAGAAAGC CUGAUGA X GAA AAAAUACU




AGUAUUUUA GCUUUGUG













5299




AAGCCACA CUGAUGA X GAA AGCUAAAA




UUUUAGCUU UGUGGCUU













5300




GAAGCCAC CUGAUGA X GAA AAGCUAAA




UUUAGCUUU GUGGUUUC













5307




CCAUCAGG CUGAUGA X GAA AGCCACAA




UUGUGGCUU CCUGAUGG













5308




GCCAUCAG CUGAUGA X GAA AAGCCACA




UGUGGCUUC CUGAUGGC













5325




CCAAUUAA CUGAUGA X GAA AUUUUUCU




AGAAAAAUC UUAAUUGG













5327




AACCAAUU CUGAUGA X GAA AGAUUUUU




AAAAAUCUU AAUUGGUU













5328




CAACCAAU CUGAUGA X GAA AAGAUUUU




AAAAUCUUA AUUGGUUG













5331




AACCAACC CUGAUGA X GAA AUUAAGAU




AUCUUAAUU GGUUGGUU













5335




AGCAAACC CUGAUGA X GAA ACCAAUUA




UAAUUGGUU GCUUUGCU













5339




GGAGAGCA CUGAUGA X GAA ACCAACCA




UGGUUGGUU UGCUCUCC













5340




UGGAGAGC CUGAUGA X GAA AACCAACC




GGUUGGUUU GCUCUCCA













5344




UAUCUGGA CUGAUGA X GAA AGCAAACC




GGUUUGCUC UCCAGAUA













5346




AUUAUCUG CUGAUGA X GAA AGAGCAAA




UUUGCUCUC CAGAUAAU













5352




CUAGUGAU CUGAUGA X GAA AUCUGGAG




CUCCAGAUA AUCACUAG













5355




UGGCUAGU CUGAUGA X GAA AUUAUCUG




CAGAUAAUC ACUAGCCA













5359




AAUCUGGC CUGAUGA X GAA AGUGAUUA




UAAUCACUA GCCAGAUU













5367




AAUUUCGA CUGAUGA X GAA AUCUGGCU




AGCCAGAUU UCGAAAUU













5368




UAAUUUCG CUGAUGA X GAA AAUCUGGC




GCCAGAUUU CGAAAUUA













5369




GUAAUUUC CUGAUGA X GAA AAAUCUGG




CCAGAUUUC GAAAUUAC













5375




UAAAAAGU CUGAUGA X GAA AUUUCGAA




UUCGAAAUU ACUUUUUA













5376




CUAAAAAG CUGAUGA X GAA AAUUUCGA




UCGAAAUUA CUUUUUAG













5379




CGGCUAAA CUGAUGA X GAA AGUAAUUU




AAAUUACUU UUUAGCCG













5380




UCGGCUAA CUGAUGA X GAA AAGUAAUU




AAUUACUUU UUAGCCGA













5381




CUCGGCUA CUGAUGA X GAA AAAGUAAU




AUUACUUUU UAGCCGAG













5382




CCUCGGCU CUGAUGA X GAA AAAAGUAA




UUACUUUUU AGCCGAGG













5383




ACCUCGGC CUGAUGA X GAA AAAAAGUA




UACUUUUUA GCCGAGGU













5392




GUUAUCAU CUGAUGA X GAA ACCUCGGC




GCCGAGGUU AUGAUAAC













5393




UGUUAUCA CUGAUGA X GAA AACCUCGG




CCGAGGUUA UGAUAACA













5398




GUAGAUGU CUGAUGA X GAA AUCAUAAC




GUUAUGAUA ACAUCUAC













5403




AUACAGUA CUGAUGA X GAA AUGUUAUC




GAUAACAUC UACUGUAU













5405




GGAUACAG CUGAUGA X GAA AGAUGUUA




UAACAUCUA CUGUAUCC













5410




CUAAAGGA CUGAUGA X GAA ACAGUAGA




UCUACUGUA UCCUUUAG













5412




UUCUAAAG CUGAUGA X GAA AUACAGUA




UACUGUAUC CUUUAGAA













5415




AAAUUCUA CUGAUGA X GAA AGGAUACA




UGUAUCCUU UAGAAUUU













5416




AAAAUUCU CUGAUGA X GAA AAGGAUAC




GUAUCCUUU AGAAUUUU













5417




UAAAAUUC CUGAUGA X GAA AAAGGAUA




UAUCCUUUA GAAUUUUA













5422




UAGGUUAA CUGAUGA X GAA AUUCUAAA




UUUAAAAUU UUAACCUA













5423




AUAGGUUA CUGAUGA X GAA AAUUCUAA




UUAGAAUUU UAACCWU













5424




UAUAGGUU CUGAUGA X GAA AAAUUCUA




UAGAAUUUU AACCUAUA













5425




UUAUAGGU CUGAUGA X GAA AAAAUUCU




AGAAUUUUA ACCUAUAA













5430




UAGUUUGA CUGAUGA X GAA AGGUUAAA




UUUAACCUA UAAAACUA













5432




CAUAGUUU CUGAUGA X GAA AUAGGUGA




UAACCUAUA AAACUAUG













5438




AGUAGACA CUGAUGA X GAA AGUUUUAU




AUAAAACUA UGUCUACU













5442




AACCAGUA CUGAUGA X GAA ACAUAGUU




AACUAUGUC UACUGGUU













5444




GAAACCAG CUGAUGA X GAA AGACAUAG




CUAUGUCUA CUGGUUUC













5450




CAGGCAGA CUGAUGA X GAA ACCAGUAG




CUACUGGUU UCUGCCUG













5451




ACAGGCAG CUGAUGA X GAA AACCAGUA




UACUGGUUU CUGCCUGU













5452




CACAGGCA CUGAUGA X GAA AAACCAGU




ACUGGUUUC UGCCUGUG











Where “X” represents stem II region of a HH ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20 3252). The length of stem II may be ≧2 base-pairs.





















TABLE VII











Mouse flk-1 VEGF receptor-Hairpin Ribozyme and Substrate Sequences













nt.








Position




HP Ribozyme Sequences




Substrate









  74




GGGACACA AGAA GGGCCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGGCCCA GAC UGUGUCCC













  88




GUUAUCCC AGAA GCGGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCCCGCA GCC GGGAUAAC













 105




GGAAUCGG AGAA GCCAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUGGCU GAC CCGAUUCC













 110




UCCGCGGA AGAA GGUCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGACCC GAU UCCGCGGA













 125




CGGCUGUC AGAA GUGUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGACACC GCU GACAGCCG













 132




CCAGCCGC AGAA GUCAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUGACA GCC GCGGCUGG













 138




CUGGCUCC AGAA GCGGCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGCCGCG GCU GGAGCCAG













 175




CAGCGCAA AGAA GGGGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCCCCG GUC UUGCGCUG













 199




GUCACAGA AGAA GUAUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCAUACC GCC UCUGUGAC













 309




CACAGAGC AGAA GCUAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUAGCU GUC GCUCUGUG













 342




CCCACAGA AGAA GCUCGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCGAGCC GCC UCUGUGGG













 434




UGCAAGUA AGAA GAAGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCCUUCA GAU UACUUGCA













 630




UAGACAUA AGAA GUGGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCCACU GUU UAUGUCUA













 655




GAAUGGUG AGAA GUAAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAUUACA GAU CACCAUUC













 739




CGACCCUC AGAA GGGGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUCCCCU GCC GAGGGUCG













 807




CUGUUUCC AGAA GGAACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUUCCG GAU GGAAACAG













 920




ACAUGAUA AGAA GAUAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUAUCA GUC UAUCAUGU













1002




UUUUCUCC AGAA GAUAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUAUCU GCC GGAGAAAA













1229




UCUUGAUC AGAA GUCCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUGGACG GAU GAUCAAGA













1365




AUAUCAGG AGAA GGGUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUACCCA GCU CCUGAUAU













1556




UCUCACCG AGAA GGGGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACCCCA GAU CGGUGAGA













1629




UUGGCGUA AGAA GUGCAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUGCACA GUC UACGCCAA













1687




UCUGUAGG AGAA GGCUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAAGCCU GCU CCUACAGA













1696




UUGGCCGG AGAA GUAGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCCUACA GAC CCGGCCAA













1796




UUCCUUCA AGAA GGGCAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUGCCCU GAU UGAAGGAA













1950




GGCUGGGC AGAA GGUUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCAACCU GCU GCCCAGCC













1953




GUUGGCUG AGAA GCAGGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACCUGCU GCC CAGCCAAC













1985




CAGUGCAC AGAA GGGACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUCCCU GUU GUGCACUG













2055




CCCAUGUG AGAA GAUGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AACAUCG GUC CACAUGGG













2082




UUCUUGCA AGAA GGUGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACACCA GUU UGCAAGAA













2208




UUAUCUUG AGAA GAGCAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUGCUCU GCU CAAGAUAA













2252




GGAUGAUG AGAA GUUUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCAAACA GCU CAUCAUCC













2444




UGCGGAUA AGAA GGUUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAACCU GAC UAUCCGCA













2639




GCUUAACG AGAA GUAGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCCUACG GAC CGUUAAGC













2703




GGCAAUUC AGAA GGAUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAUCCA GAU GAAUUGCC













2777




CUAGUUUC AGAA GGUCCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGGACCG GCU GAAACUAG













2832




CCAAAAGC AGAA GCCUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAGGCA GAC GCUUUUGG













3199




AAAGCCUG AGAA GGCAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUGCCA GCU CAGCCUUU













3278




GCUCCAAG AGAA GGAAGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACUUCCU GAC CUUGGAGC













3304




CACUUGGA AGAA GUAACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUUACA GCU UCCAAGUG













3421




CCGGGCCA AGAA GAAGUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GACUUCG GCU UGGCCCGG













3450




CUGACAUA AGAA GGGUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGACCCG GAU UAUGUCAG













3475




CAAAGGGA AGAA GGCAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAUGCCC GAC UCCCUUUG













3663




GUAGUGUA AGAA GGAGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCUCCU GAC UACACUAC













3689




CCAGCAUG AGAA GGUACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUACCA GAC CAUGCUGG













3703




CUCAUGCC AGAA GUCCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGGACU GCU GGCAUGAG













3860




GUGAGGUA AGAA GGGAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUCCCU GCC UACCUCAC













3873




AUACAGGA AGAA GGUGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCACCU GUU UCCUGUAU













4038




UGGCUGUC AGAA GGGAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAUCCCA GAU GACAGCCA













4181




AGCCACUG AGAA GGUUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCAACCA GAC CAGUGGCU













4196




GAUACCCA AGAA GGUAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUACCA GUC UGGGUAUC













4212




UCUGUGUC AGAA GAGUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCACUCA GAU GACACAGA













4278




UCAGCGUG AGAA GCAGCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGCUGCA GUU CACGCUGA













4287




GUCCCUGA AGAA GCGUGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCACGCU GAC UCAGGGAC













4307




AGGAGGUG AGAA GCAGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACUGCA GCU CACCUCCU













4318




UCCAUUUA AGAA GGAGGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACCUCCU GUU UAAAUGGA













4338




GGAGCCGG AGAA GGACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGUCCU GUC CCGGCUCC













4344




GGGGGCGG AGAA GGGACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUCCCG GCU CCGCCCCC













4349




GAGUUGGG AGAA GAGCCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CGGGUCC GCC CCCAACUC













4383




AAAAUCUA AGAA GCACCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGGUGCU GCU UAGAUUUU













4462




UCCUUGCA AGAA GAGGUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GACCUCA GAC UGCAAGGA













4574




GAGACCAC AGAA GGGCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUGCCCU GCU GUGGUCUC













4626




UCUUGGAG AGAA GAGUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGACUCU GUC CUCCAAGA













4723




CCAAGGUA AGAA GACUCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CGAGUCU GUC UACCUUGG













4823




CAGGCUCC AGAA GCUCUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAGAGCG GUU GGAGCCUG













4836




CACAAUGC AGAA GCAGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCCUGCA GAU GCAUUGUG













4896




ACCCUGCC AGAA GCCUUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAAGGCG GCC GGCAGGGU













4938




UGUAACCC AGAA GUGAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUCACA GUC GGGUUACA













4996




ACGUAAGA AGAA GGAAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUUCCG GAC UCUUACGU













5042




AAGGAGCA AGAA GCAUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAUGCA GCU UGCUCCUU













5118




UCGGCCCC AGAA GGAGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCUCCU GAC GGGGCCGA













5165




CUCCACCC AGAA GAAACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




G(GGJCU GCU CGGUGGAG













5310




UUUCUGCC AGAA GGAAGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCUUCCU GAU GGCAGAAA













5363




AUUUCGAA AGAA GGCUAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUAGCCA GAU UUCGAAAU













5453




AGCACACA AGAA GAAACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGUUUCU GCC UGUGUGGU



















Table VIII











Mouse flt-l VEGF Receptor-Hammerhead Ribozyme and






Substrate Sequence













nt.








Position




HH Ribozyme




Substrate









  17




GUGAGCAA CUGAUGU X GAA ACGCGGCC




GGCCGCGUC UUGCUCAC













  19




UGGUGAGC CUGAUGU X GAA AGACGCGG




CCGCGUCUU GCUCACCA













  23




ACCAUGGU CUGAUGU X GAA AGCAAGAC




GUCUUGCUC ACCAUGGU













  32




CAGCAGCU CUGAUGU X GAA ACCAUGGU




ACCAUGGUC AGCUGCUG













  53




UAAGGCAA CUGAUGU X GAA ACCGCGGU




ACCGCGGUC UUGCCUUA













  55




CGUAAGGC CUGAUGU X GAA AGACCGCG




CGCGGUCUU GCCUUACG













  60




CAGCGCGU CUGAUGU X GAA AGGCAAGA




UCUUGCCUU ACGCGCUG













  61




GCAGCGCG CUGAUGU X GAA AAGGCAAG




CUUGCCUUA CGCGCUGC













  71




AGACACCC CUGAUGU X GAA AGCAGCGC




GCGCUGCUC GGGUGUCU













  78




GAGAAGCA CUGAUGU X GAA ACACCCGA




UCGGGUGUC UGCUUCUC













  83




CCUGUGAG CUGAUGU X GAA AGCAGACA




UGUCUGCUU CUCACAGG













  84




UCCUGUGA CUGAUGU X GAA AAGCAGAC




GUCUGCUUC UCACAGGA













  86




UAUCCUGU CUGAUGU X GAA AGAAGCAG




CUGCUUCUC ACAGGAUA













  94




CUGAGCCA CUGAUGU X GAA AUCCUGUG




CACAGGAUA UGGCUCAG













 100




UCGACCCU CUGAUGU X GAA AGCCAUAU




AUAUGGCUC AGGGUCGA













 106




UUAACUUC CUGAUGU X GAA ACCCUGAG




CUCAGGGUC GAAGUUAA













 112




GCACUUUU CUGAUGU X GAA ACUUCGAC




GUCGAAGUU AAAAGUGC













 113




GGCACUUU CUGAUGU X GAA AACUUCGA




UCGAAGUUA AAAGUGCC













 132




GCCUUUUA CUGAUGU X GAA ACUCAGUU




AACUGAGUU UAAAAGGC













 133




UGCCUUUU CUGAUGU X GAA AACUCAGU




ACUGAGUUU AAAAGGCA













 134




GUGCCUUU CUGAUGU X GAA AAACUCAG




CUGAGUUUA AAAGGCAC













 152




GCUUGCAU CUGAUGU X GAA ACAUGCUG




CAGCAUGUC AUGCAAGC













 171




GAGAAAGA CUGAUGU X GAA AGUCUGGC




GCCAGACUC UCUUUCUC













 173




UUGAGAAA CUGAUGU X GAA AGAGUCUG




CAGACUCUC UUUCUCAA













 175




ACUUGAGA CUGAUGU X GAA AGAGAGUC




GACUCUCUU UCUCAAGU













 176




CACUUGAG CUGAUGU X GAA AAGAGAGU




ACUCUCUUU CUCAAGUG













 177




GCACUUGA CUGAUGU X GAA AAAGAGAG




CUCUCUUUC UCAAGUGC













 179




CUGCACUU CUGAUGU X GAA AGAAAGAG




CUCUUUCUC AAGUGCAG













 205




GAGACCAU CUGAUGU X GAA AGUGGGCU




AGCCCACUC AUGGUCUC













 211




UGGGCAGA CUGAUGU X GAA ACCAUGAG




CUCAUGGUC UCUGCCCA













 213




CGUGGGCA CUGAUGU X GAA AGACCAUG




CAUGGUCUC UGCCCACG













 254




GGGGGAGU CUGAUGU X GAA AUGCUCAG




CUGAGCAUC ACUCCCCC













 258




CGAUGGGG CUGAUGU X GAA AGUGAUGC




GCAUCACUC CCCCAUCG













 265




CACAGGCC CUGAUGU X GAA AUGGGGGA




UCCCCCAUC GGCCUGUG













 282




UUGCCUGU CUGAUGU X GAA AUCCCUCC




GGAGGGAUA ACAGGCAA













 292




UGCUGCAG CUGAUGU X GAA AUUGCCUG




CAGGCAAUU CUGCAGCA













 293




GUGCUGCA CUGAUGU X GAA AAUUGCCU




ACCCAAUUC UGCAGCAC













 304




CCAAGGUC CUGAUGU X GAA AGGUGCUG




CAGCACCUU GACCUUGG













 310




CCGUGUCC CUGAUGU X GAA AGGUCAAG




CUUGACCUU GGACACGG













 341




CAGGUGUA CUGAUGU X GAA AGGCCCGU




ACGGGCCUC UACACCUG













 343




UACAGGUG CUGAUGU X GAA AGAGGCCC




GGGCCUCUA CACCUGUA













 351




GAGGUAUC CUGAUGU X GAA ACAGGUGU




ACACCUGUA GAUACCUC













 355




UAGGGAGG CUGAUGU X GAA AUCUACAG




CUGUAGAUC CCUCCCUA













 359




GAUGUAGG CUGAUGU X GAA AGGUAUCU




AGAUACCUC CCUACAUC













 363




AGUAGAUG CUGAUGU X GAA AGGGAGGU




ACCUCCCUA CAUCUACU













 367




UCGAAGUA CUGAUGU X GAA AUGUAGGG




CCCUACAUC UACUUCGA













 369




CUUCGAAG CUGAUGU X GAA AGAUGUAG




CUACAUCUA CUUCGAAG













 372




UUUCUUCG CUGAUGU X GAA AGUAGAUG




CAUCUACUU CGAAGAAA













 373




UUUUCUUC CUGAUGU X GAA AAGUAGAU




AUCUACUUC GAAGAAAA













 394




AGAUUGAA CUGAUGU X GAA AUUCCGCU




AGCGGAAUC UUCAAUCU













 396




GUAGAUUG CUGAUGU X GAA AGAUUCCG




CGGAAUCUU CAAUCUAC













 397




UGUAGAUU CUGAUGU X GAA AAGAUUCC




GGAAUCUUC AAUCUACA













 401




AAUAUGUA CUGAUGU X GAA AUUGAAGA




UCUUCAAUC UACAUAUU













 403




CAAAUAUG CUGAUGU X GAA AGAUUGAA




UUCAAUCUA CAUAUUUG













 407




CUAACAAA CUGAUGU X GAA AUGUAGAU




AUCUACAUA UUUGUUAG













 409




CACUAACA CUGAUGU X GAA AUAUGUAG




CUACAUAUU UGUUAGUG













 410




UCACUAAC CUGAUGU X GAA AAUAUGUA




UACAUAUUU GUUAGUGA













 413




GCAUCACU CUGAUGU X GAA ACAAAUAU




AUAUUUGUU AGUGAUGC













 414




UGCAUCAC CUGAUGU X GAA AACAAAUA




UAUUUGUUA GUGAUGCA













 429




UAUGAAAG CUGAUGU X GAA ACUCCCUG




CAGGGAGUC CUUUCAUA













 432




CUCUAUGA CUGAUGU X GAA AGGACUCC




GGAGUCCUU UCAUAGAG













 433




UCUCUAUG CUGAUGU X GAA AAGGACUC




GAGUCCUUU CAUAGAGA













 434




AUCUCUAU CUGAUGU X GAA AAAGGACU




AGUCCUUUC AUAGAGAU













 437




UGCAUCUC CUGAUGU X GAA AUGAAAGG




CCUUUCAUA GAGAUGCA













 455




AGUUUGGG CUGAUGU X GAA AUGUCAGU




ACUGACAUA CCCAAACU













 464




AUGUGCAC CUGAUGU X GAA AGUUUGGG




CCCAAACUU GUGCACAU













 491




GGGAUGAU CUGAUGU X GAA AGCUGUCU




AGACAGCUC AUCAUCCC













 494




CAGGGGAU CUGAUGU X GAA AUGAGCUC




CAGCUCAUC AUCCCCUG













 497




CGGCAGGG CUGAUGU X GAA AUGAUGUG




CUCAUCAUC CCCUGCCG













 514




CGUUGGGU CUGAUGU X GAA ACGUCACC




GGUGACGUC ACCCAACG













 524




GUGACUGU CUGAUGU X GAA ACGUUGGG




CCCAACGUC ACAGUCAC













 530




UUUAGGGU CUGAUGU X GAA ACUGUGAC




GUCACAGUC ACCCUAAA













 536




AACUUUUU CUGAUGU X GAA AGGGUGAC




GUCACCCUA AAAAAGUU













 544




CAAAUGGA CUGAUGU X GAA ACUUUUUU




AAAAAAGUU UCCAUUUG













 545




UCAAAUGG CUGAUGU X GAA AACUUUUU




AAAAAGUUU CCAUUUGA













 546




AUCAAAUG CUGAUGU X GAA AAACUUUU




AAAAGUUUC CAUUUGAU













 550




GAGUAUCA CUGAUGU X GAA AUGGAAAC




GUUUCCAUU UGAUACUC













 551




AGAGUAUC CUGAUGU X GAA AAUGGAAA




UUUCCAUUU GAUACUCU













 555




GGUAAGAG CUGAUGU X GAA AUCAAAUG




CAUUUGAUA CUCUUACC













 558




AGGGGUAA CUGAUGU X GAA AGUAUCAA




UUGAUACUC UUACCCCU













 560




UCAGGGGU CUGAUGU X GAA AGAGUAUC




GAUACUCUU ACCCCUGA













 561




AUCAGGGG CUGAUGU X GAA AAGAGUAU




AUACUCUUA CCCCUGAU













 581




UCCCAUGU CUGAUGU X GAA AUUCUUUG




CAAAGAAUA ACAUGGGA













 594




GCCUCUCC CUGAUGU X GAA ACUGUCCC




GGGAGAGUA GGAGAGGC













 604




CUAUUAUA CUGAUGU X GAA AGCCUCUC




GAGAGGCUU UAUAAUAG













 605




GCUAUUAU CUGAUGU X GAA AAGCCUCU




AGAGGCUUU AUAAUAGC













 606




UGCUAUUA CUGAUGU X GAA AAAGCCUC




GAGGCUUUA UAAUAGCA













 608




UUUGCUAU CUGAUGU X GAA AUAAAGCC




GGCUUUAUA AUAGCAAA













 611




GCAUUUGC CUGAUGU X GAA AUUAUAAA




UUUAUAAUA GCAAAUGC













 625




UCUCUUUG CUGAUGU X GAA ACGUUGCA




UGCAACGUA CAAAGAGA













 635




AGCAGUCC CUGAUGU X GAA AUCUCUUU




AAAGAGAUA GGACUGCU













 662




UGCCCGUU CUGAUGU X GAA ACGGUGGC




GCCACCGUC AACGGGCA













 676




UUGUCUGG CUGAUGU X GAA ACAGGUGC




GCACCUGUA CCAGACAA













 688




GGGUCAGA CUGAUGU X GAA AGUUUGUC




CAGAAACUA UCUGACCC













 690




AUGGGUCA CUGAUGU X GAA AUAGUUUG




CAAACUAUC UGACCCAU













 699




GGUCUGCC CUGAUGU X GAA AUGGGUCA




UGACCCAUC GGCAGACC













 711




UAGGAUUG CUGAUGU X GAA AUUGGUCU




AGACCAAUA CAAUCCUA













 716




ACAUCUAG CUGAUGU X GAA AUUGUAUU




AAUACAAUC CUAGAUGU













 719




UGGACAUC CUGAUGU X GAA AGGAUUGU




ACAAUCCUA GAUGUCCA













 725




CGUAUUUG CUGAUGU X GAA ACAUCUAG




CUAGAUGUC CAAAUAGC













 731




GGCGGGCG CUGAUGU X GAA AUUUGGAC




GUCCAAAUA CGCCCGCC













 758




UGCCCGUG CUGAUGU X GAA AGCAGUCU




AGACUGCUC CACGGGCA













 771




GAGGACAA CUGAUGU X GAA AGUCUGCC




GGCAGACUC UUGUCCUC













 773




UUGAGGAC CUGAUGU X GAA AGAGUCUG




CAGACUCUU GUCCUCAA













 776




CAGUUGAG CUGAUGU X GAA ACAAGAGU




ACUCUUGUC CUCAACUG













 779




GUGCAGUU CUGAUGU X GAA AGGACAAG




CUUGUCCUC AACUGCAC













 803




CUCGUAUU CUGAUGU X GAA AGCUCCGU




ACGGAGCUC AAUACGAG













 807




CACCCUCG CUGAUGU X GAA AUUGAGCU




AGCUCAAUA CGAGGGUG













 831




ACCAGGGU CUGAUGU X GAA AUUCCAGC




GCUGGAAUU ACCCUGGU













 832




UACCAGGG CUGAUGU X GAA AAUUCCAG




CUGGAAUUA CCCUGGUA













 840




AGUUGCUU CUGAUGU X GAA ACCAGGGU




ACCCUGGUA AAGCAACU













 849




UGCUCUCU CUGAUGU X GAA AGUUGCUU




AAGCAACUA AGAGAGCA













 859




GCCUUAUA CUGAUGU X GAA AUGCUCUC




GAGAGCAUC UAUAAGGC













 861




CUGCCUUA CUGAUGU X GAA AGAUGCUC




GAGCAUCUA UAAGGCAG













 863




CGCUGCCU CUGAUGU X GAA AUAGAUGC




GCAUCUAUA AGGCAGCG













 875




CUCCGGUC CUGAUGU X GAA AUCCGCUG




CAGCGGAUU GACCGGAG













 888




GUUGUGGG CUGAUGU X GAA AUGGCUCC




GGAGCCAUU CCCACAAC













 889




UGUUGUGG CUGAUGU X GAA AAUGGCUC




GAGCCAUUC CCACAACA













 904




CACUGUGG CUGAUGU X GAA ACACAUUG




CAAUGUGUU CCACAGUG













 905




ACACUGUG CUGAUGU X GAA AACACAUU




AAUGUGUUC CACAGUGU













 914




AUCUUAAG CUGAUGU X GAA ACACUGUG




CACAGUGUU CUUAAGAU













 915




GAUCUUAA CUGAUGU X GAA AACACUGU




ACAGUGUUC UUAAGAUC













 917




UUGAUCUU CUGAUGU X GAA AGAACACU




AGUGUUCUU AAGAUCAA













 918




GUUGAUCU CUGAUGU X GAA AAGAACAC




GUGUUCUUA AGAUCAAC













 923




ACAUUGUU CUGAUGU X GAA AUCUUAAG




CUUAAGAUC AACAAUGU













 953




CAGGUGUA CUGAUGU X GAA AGCCCCUU




AAGGGGCUC UACACCUG













 955




GACAGGUG CUGAUGU X GAA AGAGCCCC




GGGGCUCUA CACCUGUC













 963




CUUCACGC CUGAUGU X GAA ACAGGUGU




ACACCUGUC GCGUGAAG













 979




GGAACGAG CUGAUGU X GAA ACCCACUC




GAGUGGGUC CUCGUUCC













 982




ACUGGAAC CUGAUGU X GAA AGGACCCA




UGGGUCCUC GUUCCAGU













 985




AAGACUGG CUGAUGU X GAA ACGAGGAC




GUCCUCGUU CCAGUCUU













 986




AAAGACUG CUGAUGU X GAA AACGAGGA




UCCUCGUUC CAGUCUUU













 991




UGUUGAAA CUGAUGU X GAA ACUGGAAC




GUUCCAGUC UUUCAACA













 993




GGUGUUGA CUGAUGU X GAA AGACUGGA




UCCAGUCUU UCAACACC













 994




AGGUGUUG CUGAUGU X GAA AAGACUGG




CCAGUCUUU CAACACCU













 995




GAGGUGUU CUGAUGU X GAA AAAGACUG




CAGUCUUUC AACACCUC













1003




CAUGCACG CUGAUGU X GAA AGGUGUUG




CAACACCUC CGUGCAUG













1015




CUUUUUCA CUGAUGU X GAA ACACAUGC




GCAUGUGUA UGAAAAAG













1027




CACUGAUG CUGAUGU X GAA AUCCUUUU




AAAAGGAUU CAUCAGUG













1028




ACACUGAU CUGAUGU X GAA AAUCCUUU




AAAGGAUUC AUCAGUGU













1031




UUCACACU CUGAUGU X GAA AUGAAUCC




GGAUUCAUC AGUGUGAA













1044




CUGCUUCC CUGAUGU X GAA AUGUUUCA




UGAAACAUC GGAAGCAG













1084




GCCGAUAG CUGAUGU X GAA ACCGUCUU




AAGACGGUC CUAUCGGC













1087




ACAGCCGA CUGAUGU X GAA AGGACCGU




ACGGUCCUA UCGGCUGU













1089




GGACAGCC CUGAUGU X GAA AUAGGACC




GGUCCUAUC GGCUGUCC













1096




CUUUCAUG CUGAUGU X GAA ACAGCCGA




UCGGCUGUC CAUGAAAG













1114




GGGAGGGG CUGAUGU X GAA AGGCCUUC




GAAGGCCUU CCCCUCCC













1115




GGGGAGGG CUGAUGU X GAA AAGGCCUU




AAGGCCUUC CCCUCCCC













1120




UUUCUGGG CUGAUGU X GAA AGGGGAAG




CUUCCCCUC CCCAGAAA













1130




AACCAUAC CUGAUGU X GAA AUUUCUGG




CCAGAAAUC GUAUGGUU













1133




UUUAACCA CUGAUGU X GAA ACGAUUUC




GAAAUCGUA UGGUUAAA













1138




CAUCUUUU CUGAUGU X GAA ACCAUACG




CGUAUGGUU AAAAGAUG













1139




CCAUCUUU CUGAUGU X GAA AACCAUAC




GUAUGGUUA AAAGAUGG













1150




UUGCAGGC CUGAUGU X GAA AGCCAUCU




AGAUGGCUC GCCUGCAA













1162




CAGACUUC CUGAUGU X GAA AUGUUGCA




UGCAACAUU GAAGUCUG













1168




AGCGAGCA CUGAUGU X GAA ACUUCAAU




AUUGAAGUC UGCUCGCU













1173




CAAAUAGC CUGAUGU X GAA AGCAGACU




AGUCUGCUC GCUAUUUG













1177




GUACCAAA CUGAUGU X GAA AGCGAGCA




UGCUCGCUA UUUGGUAC













1179




AUGUACCA CUGAUGU X GAA AUAGCGAG




CUCGCUAUU UGGUACAU













1180




CAUGUACC CUGAUGU X GAA AAUAGCGA




UCGCUAUUU GGUACAUG













1184




UAGCCAUG CUGAUGU X GAA ACCAAAUC




UAUUUGGUA CAUGGCUA













1192




UUAAUGAG CUGAUGU X GAA AGCCAUGU




ACAUGGCUA CUCAUUAA













1195




UAAUUAAU CUGAUGU X GAA AGUAGCCA




UGGCUACUC AUUAAUUA













1198




UGAUAAUU CUGAUGU X GAA AUGAGUAG




CUACUCAUU AAUUAUCA













1199




UUGAUAAU CUGAUGU X GAA AAUGAGUA




UACUCAUUA AUUAUCAA













1202




UCUUUGAU CUGAUGU X GAA AUUAAUGA




UCAUUAAUU AUCAAAGA













1203




AUCUUUGA CUGAUGU X GAA AAUUAAUG




CAUUAAUUA UCAAAGAU













1205




ACAUCUUU CUGAUGU X GAA AUAAUUAA




UUAAUUAUC AAAGAUGU













1237




AGAUCGUA CUGAUGU X GAA AGUCCCCU




AGGGGACUA UACGAUCU













1239




CAAGAUCG CUGAUGU X GAA AUAGUCCC




GGGACUAUA CGAUCUUG













1244




CCCAGCAA CUGAUGU X GAA AUCGUAUA




UAUACGAUC UUGCUGGG













1246




UGCCCAGC CUGAUGU X GAA AGAUCGUA




UACGAUCUU GCUGGGCA













1256




GACUGCUU CUGAUGU X GAA AUGCCCAG




CUGGGCAUA AAGCAGUC













1264




AUAGCCUU CUGAUGU X GAA ACUGCUUU




AAAGCAGUC AAGGCUAU













1271




UUUUUAAA CUGAUGU X GAA AGCCUUGA




UCAAGGCUA UUUAAAAA













1273




GGUUUUUA CUGAUGU X GAA AUAGCCUU




AAGGCUAUU UAAAAACC













1274




AGGUUUUU CUGAUGU X GAA AAUAGCCU




AGGCUAUUU AAAAACCU













1275




GAGGUUUU CUGAUGU X GAA AAAUAGCC




GGCUAUUUA AAAACCUC













1283




GUGGCAGU CUGAUGU X GAA AGGUUUUU




AAAAACCUC ACUGCCAC













1293




UACAAUGA CUGAUGU X GAA AGUGGCAG




CUGCCACUC UCAUUGUA













1295




UUUACAAU CUGAUGU X GAA AGAGUGGC




GCCACUCUC AUUGUAAA













1298




ACGUUUAC CUGAUGU X GAA AUGAGAGU




ACUCUCAUU GUAAACGU













1301




UUCACGUU CUGAUGU X GAA ACAAUGAG




CUCAUUGUA AACGUGAA













1314




GUAGAUCU CUGAUGU X GAA AGGUUUCA




UGAAACCUC AGAUCUAC













1319




UUUUCGUA CUGAUGU X GAA AUCUGAGG




CCUCAGAUC UACGAAAA













1321




ACUUUUCG CUGAUGU X GAA AGAUCUGA




UCAGAUCUA CGAAAAGU













1330




AGGACACG CUGAUGU X GAA ACUUUUCG




CGAAAAGUC CGUGUCCU













1336




GAAGCGAG CUGAUGU X GAA ACACGGAC




GUCCGUGUC CUCGCUUC













1339




UUGGAAGC CUGAUGU X GAA AGGACACG




CGUGUCCUC GCUUCCAA













1343




GGGCUUGG CUGAUGU X GAA AGCGAGGA




UCCUCGCUU CCAAGCCC













1344




UGGGCUUG CUGAUGU X GAA AAGCGAGG




CCUCGCUUC CAAGCCCA













1356




CGGAUAGA CUGAUGU X GAA AGGUGGGC




GCCCACCUC UCUAUCCG













1358




AGCGGAUA CUGAUGU X GAA AGAGGUGG




CCACCUCUC UAUCCGCU













1360




CCAGCGGA CUGAUGU X GAA AGAGAGGU




ACCUCUCUA UCCGCUGG













1362




GCCCAGCG CUGAUGU X GAA AUAGAGAG




CUCUCUAUC CGCUGGGC













1382




CAAGUGAG CUGAUGU X GAA ACUUGUCU




AGACAAGUC CUCACUUG













1385




GUGCAAGU CUGAUGU X GAA AGGACUUG




CAAGUCCUC ACUUGCAC













1389




CACGGUGC CUGAUGU X GAA AGUGAGGA




UCCUCACUU GCACCGUG













1399




GGAUGCCA CUGAUGU X GAA ACACGGUG




CACCGUGUA UGGCAUCC













1406




GGCCGAGG CUGAUGU X GAA AUGCCAUA




UAUGGCAUC CCUCGGCC













1410




UGUUGGCC CUGAUGU X GAA AGGGAUGC




GCAUCCCUC GGCCAACA













1421




AGCCACGU CUGAUGU X GAA AUUGUUGG




CCAACAAUC ACGUGGCU













1430




GGGUGCCA CUGAUGU X GAA AGCCACGU




ACGUGGCUC UGGCACCC













1443




AUUGUGGU CUGAUGU X GAA ACAGGGGU




ACCCCUGUC ACCACAAU













1452




UUUGGAGU CUGAUGU X GAA AUUGUGGU




ACCACAAUC ACUCCAAA













1456




UUUCUUUG CUGAUGU X GAA AGUGAUUG




CAAUCACUC CAAAGAAA













1468




AGAAGUCA CUGAUGU X GAA ACCUUUCU




AGAAAGGUA UGACUUCU













1474




CAGUGCAG CUGAUGU X GAA AGUCAUAC




GUAUGACUU CUGCACUG













1475




UCAGUGCA CUGAUGU X GAA AAGUCAUA




UAUGACUUC UGCACUGA













1495




GGAUAAAG CUGAUGU X GAA AUUCUUCA




UGAAGAAUC CUUUAUCC













1498




CCAGGAUA CUGAUGU X GAA AGGAUUCU




AGAAUCCUU UAUCCUGG













1499




UCCAGGAU CUGAUGU X GAA AAGGAUUC




GAAUCCUUU AUCCUGGA













1500




AUCCAGGA CUGAUGU X GAA AAAGGAUU




AAUCCUUUA UCCUGGAU













1502




GGAUCCAG CUGAUGU X GAA AUAAAGGA




UCCUUUAUC CUGGAUCC













1509




GCUGCUGG CUGAUGU X GAA AUCCAGGA




UCCUGGAUC CCAGCAGC













1522




UGUUUCCU CUGAUGU X GAA AGUUGCUG




CAGCAAGUU AGGAAACA













1523




CUGUUUCC CUGAUGU X GAA AAGUUGCU




AGCAACUUA GGAAACAG













1535




AUGCUCUC CUGAUGU X GAA AUUCUGUU




AACAGAAUU GAGAGCAU













1544




CGCUGAGA CUGAUGU X GAA AUGCUCUC




GAGAGCAUC UCUCAGCG













1546




UGCGCUGA CUGAUGU X GAA AGAUGCUC




AGACAUCUC UCAGCGCA













1548




CAUGCGCU CUGAUGU X GAA AGAGAUGC




GCAUCUCUC AGCGCAUG













1562




CCUUCUAU CUGAUGU X GAA ACCGUCAU




AUGACGGUC AUAGAAGG













1565




GUUCCUUC CUGAUGU X GAA AUGACCGU




ACGGUCAUA GAAGGAAC













1578




AACCGUCU CUGAUGU X GAA AUUUGUUC




GAACAAAUA AGACGGUU













1586




AAUGUGCU CUGAUGU X GAA ACCGUCUU




AAGACGGUU AGCACAUU













1587




CAAUGUGC CUGAUGU X GAA AACCGUCU




AGACGGUUA GCACAUUG













1594




CCACCACC CUGAUGU X GAA AUGUGCUA




UAGCACAUU GGUGGUGG













1609




GGGUCUGA CUGAUGU X GAA AGUCAGCC




GGCUGACUC UCAGACCC













1611




AGGGGUCU CUGAUGU X GAA AGAGUCAG




CUGACUCUC AGACCCCU













1625




CAGCUGUA CUGAUGU X GAA AUUCCAGG




CCUGGAAUC UACAGCUG













1627




GGCAGCUG CUGAUGU X GAA AGAUUCCA




UGGAAUCUA CAGCUGCC













1642




UUUUAUUG CUGAUGU X GAA AGGCCCGG




CCGGGCCUU CAAUAAAA













1643




AUUUUAUU CUGAUGU X GAA AAGGCCCG




CGGGCCUUC AAUAAAAU













1647




CCCUAUUU CUGAUGU X GAA AUUGAAGG




CCUUCAAUA AAAUAGGG













1652




ACAGUCCC CUGAUGU X GAA AUUUUAUU




AAUAAAAUA GGGACUGU













1673




UAAAAUUU CUGAUGU X GAA AUGUUUCU




AGAAACAUA AAAUUUUA













1678




UGACAUAA CUGAUGU X GAA AUUUUAUG




CAUAAAAUU UUAUGUCA













1679




GUGACAUA CUGAUGU X GAA AAUUUUAU




AUAAAAUUU UAUGUCAC













1680




UGUGACAU CUGAUGU X GAA AAAUUUUA




UAAAAUUUU AUGUCACA













1681




CUGUGACA CUGAUGU X GAA AAAAUUUU




AAAAUUUUA UGUCACAG













1685




ACAUCUGU CUGAUGU X GAA ACAUAAAA




UUUUAUGUC ACAGAUGU













1705




AAACGUGA CUGAUGU X GAA AGCCAUUC




GAAUGGCUU UCACGUUU













1706




GAAACGUG CUGAUGU X GAA AAGCCAUU




AAUGGCUUU CACGUUUC













1707




GGAAACGU CUGAUGU X GAA AAAGCCAU




AUGGCUUUC ACGUUUCC













1712




UCCAAGGA CUGAUGU X GAA ACGUGAAA




UUUCACGUU UCCUUGGA













1713




UUCCAAGG CUGAUGU X GAA AACGUGAA




UUCACGUUU CCUUGGAA













1714




UUUCCAAG CUGAUGU X GAA AAACGUGA




UCACGUUUC CUUGGAAA













1717




UCUUUUCC CUGAUGU X GAA AGGAAACG




CGUUUCCUU GGAAAAGA













1756




CCACACAG CUGAUGU X GAA ACAGUUUC




GAAACUGUC CUGUGUGG













1766




AAUUUAUU CUGAUGU X GAA ACCACACA




UGUGUGGUC AAUAAAUU













1770




CAGGAAUU CUGAUGU X GAA AUUGACCA




UGGUCAAUA AAUUCCUG













1774




UGUACAGG CUGAUGU X GAA AUUUAUUG




CAAUAAAUU CCUGUACA













1775




CUGUACAG CUGAUGU X GAA AAUUUAUU




AAUAAAUUC CUGUACAG













1780




UGUCUCUG CUGAUGU X GAA ACAGGAAU




AUUCCUGUA CAGAGACA













1790




AUCCAGGU CUGAUGU X GAA AUGUCUCU




AGAGACAUU ACCUGGAU













1791




AAUCCAGG CUGAUGU X GAA AAUGUCUC




GAGACAUUA CCUGGAUU













1799




GGUAGCAG CUGAUGU X GAA AUCCAGGU




ACCUGGAUU CUGCUACG













1800




CCGUAGCA CUGAUGU X GAA AAUCCAGG




CCUGGAUUC UGCUACGG













1805




ACUGUCCG CUGAUGU X GAA AGCAGAAU




AUUCUGCUA CGGACAGU













1814




CUGUUGUU CUGAUGU X GAA ACUGUCCG




CGGACAGUU AACAACAG













1815




UCUGUUGU CUGAUGU X GAA AACUGUCC




GGACAGUUA ACAACAGA













1836




GCUGAUAC CUGAUGU X GAA AUGGUGCA




UGCACCAUA GUAUCAGC













1839




CUUGCUGA CUGAUGU X GAA ACUAUGGU




ACCAUAGUA UCAGCAAG













1841




UGCUUGCU CUGAUGU X GAA AUACUAUG




CAUAGUAUC AGCAAGCA













1866




GUAAUCUU CUGAUGU X GAA AGUGGUGG




CCACCACUC AAGAUUAC













1872




GAUGGAGU CUGAUGU X GAA AUCUUGAG




CUCAAGAUU ACUCCAUC













1873




UGAUGGAG CUGAUGU X GAA AAUCUUGA




UCAAGAUUA CUCCAUCA













1876




GAGUGAUG CUGAUGU X GAA AGUAAUCU




AGAUUACUC CAUCACUC













1880




UUCAGAGU CUGAUGU X GAA AUGGAGUA




UACUCCAUC ACUCUGAA













1884




AAGGUUCA CUGAUGU X GAA AGUGAUGG




CCAUCACUC UGAACCUU













1892




UUGAUGAC CUGAUGU X GAA AGGUUCAG




CUGAACCUU GUCAUCAA













1895




UUCUUGAU CUGAUGU X GAA ACAAGGUU




AACCUUGUC AUCAAGAA













1898




ACGUUCUU CUGAUGU X GAA AUGACAAG




CUUGUCAUC AAGAACGU













1909




CUUCUAGA CUGAUGU X GAA ACACGUUC




GAACGUGUC UCUAGAAG













1911




GUCUUCUA CUGAUGU X GAA AGACACGU




ACGUGUCUC UAGAAGAC













1913




GAGUCUUC CUGAUGU X GAA AGAGACAC




GUGUCUCUA GAAGACUC













1921




AGGUGCCC CUGAUGU X GAA AGUCUUCU




AGAACACUC GGGCACCU













1930




UGCACGCA CUGAUGU X GAA AGGUGCCC




GGGCACCUA UGCGUGCA













1952




CCUGUGUA CUGAUGU X GAA AUGUUCCU




AGGAACAUA UACACAGG













1954




CCCCUGUG CUGAUGU X GAA AUAUGUUC




GAACAUAUA CACAGGGG













1970




UUCCGAAG CUGAUGU X GAA AUGUCUUC




GAAGACAUC CUUCGGAA













1973




GUCUUCCG CUGAUGU X GAA AGGAUGUC




GACAUCCUU CGGAAGAC













1974




UGUCUUCC CUGAUGU X GAA AAGGAUGU




ACAUCCUUC GGAAGACA













1988




CUAACGAG CUGAUGU X GAA ACUUCUGU




ACAGAAGUU CUCGUUAG













1989




UCUAACGA CUGAUGU X GAA AACUUCUG




CAGAAGUUC UCGUUAGA













1991




UCUCUAAC CUGAUGU X GAA AGAACUUC




GAAGUUCUC GUUAGAGA













1994




GAAUCUCU CUGAUGU X GAA ACGAGAAC




GUUCUCGUU AGAGAUUC













1995




CGAAUCUC CUGAUGU X GAA AACGAGAA




UUCUCGUUA GAGAUUCG













2001




CGCUUCCG CUGAUGU X GAA AUCUCUAA




UUAGAGAUU CGGAAGCG













2002




GCGCUUCC CUGAUGU X GAA AAUCUCUA




UAGAGAUUC GGAAGCGC













2021




AGGUUUUG CUGAUGU X GAA AGCAGGUG




CACCUGCUU CAAAACCU













2022




GAGGUUUU CUGAUGU X GAA AAGCAGGU




ACCUGCUUC AAAACCUC













2030




UAGUCACU CUGAUGU X GAA AGGUUUUG




CAAAACCUC AGUGACUA













2038




AGACCUCG CUGAUGU X GAA AGUCACUG




CAGUGACUA CGAGGUCU













2045




CUGAUGGA CUGAUGU X GAA ACCUCGUA




UACGAGGUC UCCAUCAG













2047




CACUGAUG CUGAUGU X GAA AGACCUCG




CGAGGUCUC CAUCAGUG













2051




GAGCCACU CUGAUGU X GAA AUGGAGAC




GUCUCCAUC AGUGGCUC













2059




AGGUCGUA CUGAUGU X GAA AGCCACUG




CAGUGGCUC UACGACCU













2061




UAAGGUCG CUGAUGU X GAA AGAGCCAC




GUGGCUCUA CGACCUUA













2068




GACAGUCU CUGAUGU X GAA AGGUCGUA




UACGACCUU AGACUGUC













2069




UGACAGUC CUGAUGU X GAA AAGGUCGU




ACGACCUUA GACUGUCA













2076




UCUAGCUU CUGAUGU X GAA ACAGUCUA




UAGACUGUC AAGCUAGA













2082




GACACCUC CUGAUGU X GAA AGCUUGAC




GUCAAGCUA GAGGUGUC













2090




GGCGCGGG CUGAUGU X GAA ACACCUGU




AGAGGUGUC CCCGCGCC













2100




AGUGAUCU CUGAUGU X GAA AGGCGCGG




CCGCGCCUC AGAUCACU













2105




AACCAAGU CUGAUGU X GAA AUCUGAGG




CCUCAGAUC ACUUGGUU













2109




UUUGAACC CUGAUGU X GAA AGUGAUCU




AGAUCACUU GGUUCAAA













2113




UGUUUUUG CUGAUGU X GAA ACCAAGUG




CACUUGGUU CAAAAACA













2114




UUGUUUUU CUGAUGU X GAA AACCAAGU




ACUUGGUUC AAAAACAA













2132




UCUUGUUG CUGAUGU X GAA AUUUUGUG




CACAAAAUA CAACAAGA













2150




CCUAAAAU CUGAUGU X GAA AUUCCCGG




CCGGGAAUU AUUUUAGG













2151




UCCUAAAA CUGAUGU X GAA AAUUCCCG




CGGGAAUUA UUUUAGGA













2153




GGUCCUAA CUGAUGU X GAA AUAAUUCC




GGAAUUAUU UUAGGACC













2154




UGGUCCUA CUGAUGU X GAA AAUAAUUC




GAAUUAUUU UAGGACCA













2155




CUGGUCCU CUGAUGU X GAA AAAUAAUU




AAUUAUUUU AGGACCAG













2156




CCUGGUCC CUGAUGU X GAA AAAAUAAU




AUUAUUUUA GGACCAGG













2179




UUUCAAUA CUGAUGU X GAA ACAGCGUG




CACGCUGUU UAUUGAAA













2180




CUUUCAAU CUGAUGU X GAA AACAGCGU




ACGCUGUUU AUUGAAAG













2181




UCUUUCAA CUGAUGU X GAA AAACAGCG




CGCUGUUUA UUGAAAGA













2183




ACUCUUUC CUGAUGU X GAA AUAAACAG




CUGUUUAUU GAAAGAGU













2192




UCCUCUGU CUGAUGU X GAA ACUCUUUC




GAAAGAGUC ACAGAGGA













2213




CACCUAUA CUGAUGU X GAA ACACCCUC




GAGGGUGUC UAUAGGUG













2215




GGCACCUA CUGAUGU X GAA AGACACCC




GGGUGUCUA UAGGUGCC













2217




UCGGCACC CUGAUGU X GAA AUAGACAC




GUGUCUAUA GGUGCCGA













2263




CGGUGAGG CUGAUGU X GAA AGGCUGCG




CGCAGCCUA CCUCACCG













2267




UGCACGGU CUGAUGU X GAA AGGUAGGC




GCCUACCUC ACCGUGCA













2284




ACUUGUCU CUGAUGU X GAA AGGUUCCU




AGGAACCUC AGACAAGU













2293




CCAGGUUU CUGAUGU X GAA ACUUGUCU




AGACAAGUC AAACCUGG













2309




GUGAGCGU CUGAUGU X GAA AUCAGCUC




GAGCUGAUC ACGCUCAC













2315




GUGCACGU CUGAUGU X GAA AGCGUGAU




AUCACGCUC ACGUGCAC













2342




AGCCAAAA CUGAUGU X GAA AGGGUCGC




GCGACCCUC UUUUGGCU













2344




GGAGCCAA CUGAUGU X GAA AGAGGGUC




GACCCUCUU UUGGCUCC













2345




AGGAGCCA CUGAUGU X GAA AAGAGGGU




ACCCUCUUU UGGCUCCU













2346




AAGGAGCC CUGAUGU X GAA AAAGAGGG




CCCUCUUUU GGCUCCUU













2351




GUUAGAAG CUGAUGU X GAA AGCCAAAA




UUUUGGCUC CUUCUAAC













2354




AGAGUUAG CUGAUGU X GAA AGGAGCCA




UGGCUCCUU CUAACUCU













2355




GAGAGUUA CUGAUGU X GAA AAGGAGCC




GGCUCCUUC UAACUCUC













2357




AAGAGAGU CUGAUGU X GAA AGAAGGAG




CUCCUUCUA ACUCUCUU













2361




GAUGAAGA CUGAUGU X GAA AGUUAGAA




UUCUAACUC UCUUCAUC













2363




CUGAUGAA CUGAUGU X GAA AGAGUUAG




CUAACUCUC UUCAUCAG













2365




UUCUGAUG CUGAUGU X GAA AGAGAGUU




AACUCUCUU CAUCAGAA













2366




UUUCUGAU CUGAUGU X GAA AAGAGAGU




ACUCUCUUC AUCAGAAA













2369




AGUUUUCU CUGAUGU X GAA AUGAAGAG




CUCUUCAUC AGAAAACU













2386




CGGAAGAA CUGAUGU X GAA ACCGCUUC




GAAGCGGUC UUCUUCCG













2388




UUCGGAAG CUGAUGU X GAA AGACCGCU




AGCGGUCUU CUUCCGAA













2389




CUUCGGAA CUGAUGU X GAA AAGACCGC




GCGGUCUUC UUCCGAAG













2391




UACUUCGG CUGAUGU X GAA AGAAGACC




GGUCUUCUU CCGAAGUA













2392




UUACUUCG CUGAUGU X GAA AAGAAGAC




GUCUUCUUC CGAAGUAA













2399




UCUGUCUU CUGAUGU X GAA ACUUCGGA




UCCGAAGUA AAGACAGA













2410




UUGACAGG CUGAUGU X GAA AGUCUGUC




GACAGACUA CCUGUCAA













2416




UAAUGAUU CUGAUGU X GAA ACAGGUAG




CUACCUGUC AAUCAUUA













2420




UCCAUAAU CUGAUGU X GAA AUUGACAG




CUGUCAAUC AUUAUGGA













2423




GGGUCCAU CUGAUGU X GAA AUGAUUGA




UCAAUCAUU AUGGACCC













2424




UGGGUCCA CUGAUGU X GAA AAUGAUUG




CAAUCAUUA UGGACCCA













2441




UCCAGGGG CUGAUGU X GAA ACUUCAUC




GAUGAAGUU CCCCUGGA













2442




AUCCAGGG CUGAUGU X GAA AACUUCAU




AUGAAGUUC CCCUGGAU













2473




UGGCAUCA CUGAUGU X GAA AGGGCAGC




GCUGCCCUA UGAUGCCA













2494




CCCGUGCA CUGAUGU X GAA ACUCCCAC




GUGGGAGUU UGCACGGG













2495




UCCCGUGC CUGAUGU X GAA AACUCCCA




UGGGAGUUU GCACGGGA













2516




GAUUUGCC CUGAUGU X GAA AGUUUCAG




CUGAAACUA GGCAAAUC













2524




UUCCGAGC CUGAUGU X GAA AUUUGCCU




AGGCAAAUC GCUCGGAA













2528




CCUCUUCC CUGAUGU X GAA AGCGAUUU




AAAUCGCUC GGAAGAGG













2541




UUUCCCAA CUGAUGU X GAA AGCCCCUC




GAGGGGCUU UUGGGAAA













2542




CUUUCCCA CUGAUGU X GAA AAGCCCCU




AGGGGCUUU UGGGAAAG













2543




ACUUUCCC CUGAUGU X GAA AAAGCCCC




GGGGCUUUU GGGAAAGU













2552




GCUUGAAC CUGAUGU X GAA ACUUUCCC




GGGAAAGUC GUUCAAGC













2555




GAGGCUUG CUGAUGU X GAA ACGACUUU




AAAGUCGUU CAAGCCUC













2556




AGAGGCUU CUGAUGU X GAA AACGACUU




AAGUCGUUC AAGCCUCU













2563




CAAAUGCA CUGAUGU X GAA AGGCUUGA




UCAAGCCUC UGCAUUUG













2569




UAAUGCCA CUGAUGU X GAA AUGCAGAG




CUCUGCAUU UGGCAUUA













2570




UUAAUGCC CUGAUGU X GAA AAUGCAGA




UCUGCAUUU GGCAUUAA













2576




GAUUUCUU CUGAUGU X GAA AUGCCAAA




UUUGGCAUU AAGAAAUC













2577




UGAUUUCU CUGAUGU X GAA AAUGCCAA




UUGGCAUUA AGAAAUCA













2584




AGGUGGGU CUGAUGU X GAA AUUUCUUA




UAAGAAAUC ACCCACCU













2617




CCUCUUUC CUGAUGU X GAA ACAUCUUC




GAAGAUGUU GAAAGAGG













2644




GAGCUUUG CUGAUGU X GAA ACUCACUG




CAGUGAGUA CAAAGCUC













2652




GGUCAUCA CUGAUGU X GAA AGCUUUGU




ACAAAGCUC UGAUGACC













2666




AAGAUCUU CUGAUGU X GAA AGUUCGGU




ACCGAACUC AAGAUCUU













2672




UGGGUCAA CUGAUGU X GAA AUCUUGAG




CUCAAGAUC UUGACCCA













2674




UGUGGGUC CUGAUGU X GAA AGAUCUUG




CAAGAUCUU GACCCACA













2684




UGAUGGCC CUGAUGU X GAA AUGUGGGU




ACCCACAUC GGCCAUCA













2691




AUUCAGAU CUGAUGU X GAA AUGGCCGA




AUGGCCAUC AUCUGAAU













2694




CACAUUCA CUGAUGU X GAA AUGAUGGC




GCCAUCAUC UGAAUGUG













2705




AGGAGGUU CUGAUGU X GAA ACCACAUU




AAUGUGGUU AACCUCCU













2706




CAGGAGGU CUGAUGU X GAA AACCACAU




AUGUGGUUA ACCUCCUG













2711




GCUCCCAG CUGAUGU X GAA AGGUUAAC




GUUAACCUC CUGGGAGC













2742




CACCAUCA CUGAUGU X GAA AGGCCCUC




GAGGGCCUC UGAUGGUG













2753




UAUUCCAC CUGAUGU X GAA AUCACCAU




AUGGUGAUC GUGGAAUA













2761




AUUUGCAG CUGAUGU X GAA AUUCCACG




CGUGGAAUA CUGCAAAU













2770




GGUUUCCG CUGAUGU X GAA AUUUGCAG




CUGCAAAUA AGGAAACC













2782




GGUAGUUG CUGAUGU X GAA ACAGGUUU




AAACCUGUC CAACUACC













2788




UCUUGAGG CUGAUGU X GAA AGUUGGAC




GUCCAACUA CCUCAAGA













2792




UUGCUCUU CUGAUGU X GAA AGGUAGUU




AACUACCUC AAGAGCAA













2809




GACAGAAU CUGAUGU X GAA AGUCACGU




ACGUGACUU AUUCUGUC













2810




AGACAGAA CUGAUGU X GAA AAGUCACG




CGUGACUUA UUCUGUCU













2812




UGAGACAG CUGAUGU X GAA AUAAGUCA




UGACUUAUU CUGUCUCA













2813




UUGAGACA CUGAUGU X GAA AAUAAGUC




GACUUAUUC UGUCUCAA













2817




CUUGUUGA CUGAUGU X GAA ACAGAAUA




UAUUCUGUC UCAACAAG













2819




UCCUUGUU CUGAUGU X GAA AGACAGAA




UUCUGUCUC AACAAGGA













2836




CCAUAUGC CUGAUGU X GAA AGGCUGCG




CGCAGCCUU GCAUAUGG













2841




GAGCUCCA CUGAUGU X GAA AUGCAAGG




CCUUGCAUA UGGAGCUC













2849




UCUUUCUU CUGAUGU X GAA AGCUCCAU




AUGGAGCUC AAGAAAGA













2900




ACACUGUC CUGAUGU X GAA AGGCGGGG




CCCCGCCUA GACAGUGU













2909




GAGCUGCU CUGAUGU X GAA ACACUGUC




GACAGUGUC AGCAGCUC













2917




UGACACUU CUGAUGU X GAA AGCUGCUC




CAGCAGCUC AAGUGUCA













2924




GAGCUGGU CUGAUGU X GAA ACACUUGA




UCAAGUGUC ACCAGCUC













2932




GGAAGCUG CUGAUGU X GAA AGCUGGUG




CACCAGCUC CAGCUUCC













2938




CUUCAGGG CUGAUGU X GAA AGCUGGAG




CUCCAGCUU CCCUGAAG













2939




UCUUCAGG CUGAUGU X GAA AAGCUGGA




UCCAGCUUC CCUGAAGA













2982




CUCACUGU CUGAUGU X GAA AUCCUCGU




ACGAGGAUU ACAGUGAG













2983




UCUCACUG CUGAUGU X GAA AAUCCUCG




CGAGGAUUA CAGUGAGA













2993




UGCUUGGA CUGAUGU X GAA AUCUCACU




AGUGAGAUC UCCAAGCA













2995




GCUGCUUG CUGAUGU X GAA AGAUCUCA




UGAGAUCUC CAAGCAGC













3008




UCCAUGGU CUGAUGU X GAA AGGGGCUG




CAGCCCCUC ACCAUGGA













3026




CUGUAGGA CUGAUGU X GAA AUCAGGUC




GACCUGAUU UCCUACAG













3027




ACUGUAGG CUGAUGU X GAA AAUCAGGU




ACCUGAUUU CCUACAGU













3028




AACUGUAG CUGAUGU X GAA AAAUCAGG




CCUGAUUUC CUACAGUU













3031




GGAAACUG CUGAUGU X GAA AGGAAAUC




GAUUUCCUA CAGUUUCC













3036




CACUUGGA CUGAUGU X GAA ACUGUAGG




CCUACAGUU UCCAAGUG













3037




CCACUUGG CUGAUGU X GAA AACUGUAG




CUACAGUUU CCAAGUGG













3038




GCCACUUG CUGAUGU X GAA AAACUGUA




UACAGUUUC CAAGUGGC













3061




AGGACAGA CUGAUGU X GAA ACUCCAUG




CAUGGAGUU UCUGUCCU













3062




GAGGACAG CUGAUGU X GAA AACUCCAU




AUGGAGUUU CUGUCCUC













3063




GGAGGACA CUGAUGU X GAA AAACUCCA




UGGAGUUUC UGUCCUCC













3067




UUCUGGAG CUGAUGU X GAA ACAGAAAC




GUUUCUGUC CUCCAGAA













3070




ACUUUCUG CUGAUGU X GAA AGGACAGA




UCUGUCCUC CAGAAAGU













3083




UCCCGAUG CUGAUGU X GAA AUGCACUU




AAGUGCAUU CAUCGGGA













3084




GUCCCGAU CUGAUGU X GAA AAUGCACU




AGUGCAUUC AUCGGGAC













3087




CAGGUCCC CUGAUGU X GAA AUGAAUGC




GCAUUCAUC GGGACCUG













3110




GAUAAAAG CUGAUGU X GAA AUGUUUCU




AGAAACAUC CUUUUAUC













3113




UCAGAUAA CUGAUGU X GAA AGGAUGUU




AACAUCCUU UUAUCUGA













3114




CUCAGAUA CUGAUGU X GAA AAGGAUGU




ACAUCCUUU UAUCUGAG













3115




UCUCAGAU CUGAUGU X GAA AAAGGAUG




CAUCCUUUU AUCUGAGA













3116




UUCUCAGA CUGAUGU X GAA AAAAGGAU




AUCCUUUUA UCUGAGAA













3118




UGUUCUCA CUGAUGU X GAA AUAAAAGG




CCUUUUAUC UGAGAACA













3140




AAGUCGCA CUGAUGU X GAA AUCUUCAC




GUGAAGAUU AGCGACUU













3141




AAAGUCGC CUGAUGU X GAA AAUCUUCA




UGAAGAUUU GCGACUUU













3148




CCAGGCCA CUGAUGU X GAA AGUCGCAA




UUGCGACUU AGGCCUGG













3149




GCCAGGCC CUGAUGU X GAA AAGUCGCA




UGCGACUUU GGCCUGGC













3165




CUUAUAAA CUGAUGU X GAA AUCCCGGG




CCCGGGAUA UUUAUAAG













3167




UUCUUAUA CUGAUGU X GAA AUAUCCCG




CGGGAUAUU UAUAAGAA













3168




GUUCUUAU CUGAUGU X GAA AAUAUCCC




GGGAUAUUU AUAAGAAC













3169




GGUUCUUA CUGAUGU X GAA AAAUAUCC




GGAUAUUUA UAAGAACC













3171




AGGGUUCU CUGAUGU X GAA AUAAAUAU




AUAUUUAUA AGAACCCU













3183




CCUCACAU CUGAUGU X GAA AUCAGGGU




ACCCUGAUU AUGUGAGG













3184




UCCUCACA CUGAUGU X GAA AAUCAGGG




CCCUGAUUA UGUGAGGA













3201




AAGUCGAG CUGAUGU X GAA AUCUCCUC




GAGGAGAUA CUCGACUU













3204




GGGAAGUC CUGAUGU X GAA AGUAUCUC




GAGAUACUC GACUUCCC













3209




UUUAGGGG CUGAUGU X GAA AGUCGAGU




ACUCGACUU CCCCUAAA













3210




UUUUAGGG CUGAUGU X GAA AAGUCGAG




CUCGACUUC CCCUAAAA













3215




AUCCAUUU CUGAUGU X GAA AGGGGAAG




CUUCCCCUA AAAUGGAU













3228




GGAUUCAG CUGAUGU X GAA AGCCAUCC




GGAUGGCUC CUGAAUCC













3235




CAAAGAUG CUGAUGU X GAA AUUCAGGA




UCCUGAAUC CAUCUUUG













3239




UUGUCAAA CUGAUGU X GAA AUGGAUUC




GAAUCCAUC UUUGACAA













3241




CCUUGUCA CUGAUGU X GAA AGAUGGAU




AUCCAUCUU UGACAAGG













3242




ACCUUGUC CUGAUGU X GAA AAGAUGGA




UCCAUCUUU GACAAGGU













3251




GUGCUGUA CUGAUGU X GAA ACCUUGUC




GACAAGGUC UACAGCAC













3253




UGGUGCUG CUGAUGU X GAA AGACCUUG




CAAGGUCUA CAGCACCA













3277




CGCCAUAG CUGAUGU X GAA ACCACACA




UGUGUGGUC CUAUGGCG













3280




ACACGCCA CUGAUGU X GAA AGGACCAC




GUGGUCCUA UGGCGUGU













3289




CCCACAGC CUGAUGU X GAA ACACGCCA




UGGCGUGUU GCUGUGGG













3302




AAGGAGAA CUGAUGU X GAA AUCUCCCA




UGGGAGAUC UUCUCCUU













3304




CUAAGGAG CUGAUGU X GAA AGAUCUCC




GGAGAUCUU CUCCUUAG













3305




CCUAAGGA CUGAUGU X GAA AAGAUCUC




GAGAUCUUC UCCUUAGG













3307




CCCCUAAG CUGAUGU X GAA AGAAGAUC




GAUCUUCUC CUUAGGGG













3310




AACCCCCU CUGAUGU X GAA AGGAGAAG




CUUCUCCUU AGGGGGUU













3311




GAACCCCC CUGAUGU X GAA AAGGAGAA




UUCUCCUUA GGGGGUUC













3318




GUAUGGAG CUGAUGU X GAA ACCCCCUA




UAGGGGGUU CACCAUAC













3319




GGUAUGGA CUGAUGU X GAA AACCCCCU




AGGGGGUUC UCCAUACC













3321




UGGGUAUG CUGAUGU X GAA AGAACCCC




GGGGUUCUC CAUACCCA













3325




CUCCUGGG CUGAUGU X GAA AUGGAGAA




UUCUCCAUA CCCAGGAG













3352




GGCUGCAG CUGAUGU X GAA AGUCUUCA




UGAAGACUU CUGCAGCC













3353




CGGCUGCA CUGAUGU X GAA AAGUCUUC




GAAGACUUC UGCAGCCG













3397




GUGUGGCA CUGAUGU X GAA ACUCCGGG




CCCGGAGUA UGCCACAC













3413




AUUUGGUA CUGAUGU X GAA AUUUACGG




CCUGAAAUC UACCAAAU













3415




UGAUUUGG CUGAUGU X GAA AGAUUUCA




UGAAAUCUA CCAAAUCA













3422




UCCAACAU CUGAUGU X GAA AUUUGGUA




UACCAAAUC AUGUUGGA













3427




AGCAAUCC CUGAUGU X GAA ACAUGAUU




AAUCAUGUU GGAUUGCU













3432




GUGCCAGC CUGAUGU X GAA AUCCAACA




UGUUGGAUU GCUGGCAC













3466




GUUCAGCA CUGAUGU X GAA ACCGGGGC




GCCCCGGUU UGCUGAAC













3467




AGUUCAGC CUGAUGU X GAA AACCGGGG




CCCCGGUUU GCUGAACU













3476




UUCUCCAC CUGAUGU X GAA AGUUCAGC




GCUGAACUU GUGGAGAA













3488




AGGUCACC CUGAUGU X GAA AGUUUCUC




GAGAAACUU GGUGACCU













3500




UUGGCUUG CUGAUGU X GAA AGCAGGUC




GACCUGCUU CAAGCCAA













3501




GUUGGCUU CUGAUGU X GAA AAGCAGGU




ACCUGCUUC AAGCCAAC













3512




UCCUGUUG CUGAUGU X GAA ACGUUGGC




GCCAACGUC CAACAGGA













3531




GGGGAUGU CUGAUGU X GAA AUCUUUCC




GGAAAGAUU ACAUCCCC













3532




GGGGGAUG CUGAUGU X GAA AAUCUUUC




GAAAGAUUA CAUCCCCC













3536




UUGAGGGG CUGAUGU X GAA AUGUAAUC




GAUUACAUC CCCCUCAA













3542




AUGGCAUU CUGAUGU X GAA AGGGGGAU




AUCCCCCUC AAUGCCAU













3551




CUAGUCAG CUGAUGU X GAA AUGGCAUU




AAUGCCAUA CUGACUAG













3558




ACUGUUUC CUGAUGU X GAA AGUCAGUA




UACUGACUA GAAACAGU













3567




UGUGAAGC CUGAUGU X GAA ACUGUUUC




GAAACAGUA GCUUCACA













3571




AGUAUGUG CUGAUGU X GAA ACGUACUG




CAGUAGCUU CACAUACU













3572




GAGUAUGU CUGAUGU X GAA AAGCUACU




AGUAGCUUC ACAUACUC













3577




GGGUCGAG CUGAUGU X GAA AUGUGAAG




CUUCACAUA CUCGACCC













3580




UGGGGGUC CUGAUGU X GAA AGUAUGUG




CACAUACUC GACCCCCA













3592




CCUCAGAG CUGAUGU X GAA AGGUGGGG




CCCCACCUU CUCUGAGG













3593




UCCUCAGA CUGAUGU X GAA AAGGUGGG




CCCACCUUC UCUGAGGA













3595




GGUCCUCA CUGAUGU X GAA AGAAGGUG




CACCUUCUC UGAGGACC













3605




UCCUUGAA CUGAUGU X GAA AGGUCCUC




GAGGACCUU UUCAAGGA













3606




GUCCUUGA CUGAUGU X GAA AAGGUCCU




AGGACCUUU UCAAGGAC













3607




CGUCCUUG CUGAUGU X GAA AAAGGUCC




GGACCUUUU CAAGGACG













3608




CCGUCCUU CUGAUGU X GAA AAAAGGUC




GACCUUUUC AAGGACGG













3619




GAUCUGCA CUGAUGU X GAA AGCCGUCC




GGACGGCUU UGCAGAUC













3620




GGAUCUGC CUGAUGU X GAA AAGCCGUC




GACGGCUUU GCAGAUCC













3627




AAAAUGUG CUGAUGU X GAA AUCUGCAA




UUGCAGAUC CACAUUUU













3633




GGAAUGAA CUGAUGU X GAA AUGUGGAU




AUCCACAUU UUCAUUCC













3634




CGGAAUGA CUGAUGU X GAA AAUGUGGA




UCCACAUUU UCAUUCCG













3635




CCGGAAUG CUGAUGU X GAA AAAUGUGG




CCACAUUUU CAUUCCGG













3636




UCCGGAAU CUGAUGU X GAA AAAAUGUG




CACAUUUUC AUUCCGGA













3639




GCUUCCGG CUGAUGU X GAA AUGAAAAU




AUUUUCAUU CCGGAAGC













3640




AGCUUCCG CUGAUGU X GAA AAUGAAAA




UUUUCAUUC CGGAAGCU













3649




CAUCAUCA CUGAUGU X GAA AGCUUCCG




CGGAAGCUC UGAUGAUG













3664




CGUUUACA CUGAUGU X GAA AUCUCACA




UGUGAGAUA UGUAAACG













3668




AAAGCGUU CUGAUGU X GAA ACAUAUCU




AGAUAUGUA AACGCUUU













3675




GAAUUUGA CUGAUGU X GAA AGCGUUUA




UAAACGCUU UCAAAUUC













3676




UGAAUUUG CUGAUGU X GAA AAGCGUUU




AAACGCUUU CAAAUUCA













3677




AUGAAUUU CUGAUGU X GAA AAAGCGUU




AACGCUUUC AAAUUCAU













3682




GGCUCAUG CUGAUGU X GAA AUUUCAAA




UUUCAAAUU CAUGAGCC













3683




AGGCUCAU CUGAUGU X GAA AAUUUGAA




UUCAAAUUC AUGAGCCU













3701




AAGGUUUU CUGAUGU X GAA AUUCUUUC




GAAAGAAUC AAAACCUU













3709




GCUCCUCA CUGAUGU X GAA AGGUUUUG




CAAAACCUU UGAGGAGC













3710




AGCUCCUC CUGAUGU X GAA AAGGUUUU




AAAACCUUU GAGGAGCU













3719




UUCGGUGA CUGAUGU X GAA AGCUCCUC




GAGGAGCUU UCACCGAA













3720




GUUCGGUG CUGAUGU X GAA AAGCUCCU




AGGAGCUUU CACCGAAC













3721




AGUUCGGU CUGAUGU X GAA AAAGCUCC




GGAGCUUUC ACCGAACU













3730




UGGAGGUG CUGAUGU X GAA AGUUCGGU




ACCGAACUC CACCUCCA













3736




CAAACAUG CUGAUGU X GAA AGGUGGAG




CUCCACCUC CAUGUUUG













3742




AGUCCUCA CUGAUGU X GAA ACAUGGAG




CUCCAUGUU UGAGGACU













3743




UAGUCCUC CUGAUGU X GAA AACAUGAG




UCCAUGUUU GAGGACUA













3751




CCAGCUGA CUGAUGU X GAA AGUCCUCA




UGAGGACUA UCAGCUGG













3753




GUCCAGCU CUGAUGU X GAA AUAGUCCU




AGGACUAUC AGCUGGAC













3765




CAGAGUGC CUGAUGU X GAA AGUGUCCA




UGGACACUA GCACUCUG













3771




GCCCAGCA CUGAUGU X GAA AGUGCUAG




CUAGCACUC UGCUGGGC













3781




GCAAGGGG CUGAUGU X GAA AGCCCAGC




GCUGGGCUC CCCCUUGC













3787




GCUUCAGC CUGAUGU X GAA AGGGGGAG




CUCCCCCUU GCUGAAGC













3799




UCCAGGUG CUGAUGU X GAA ACCGCUUC




GAAGCGGUU CACCUGGA













3800




GUCCAGGU CUGAUGU X GAA AACCGCUU




AAGCGGUUC ACCUGGAC













3829




UCUUCAUG CUGAUGU X GAA AGGCCUUG




CAAGGCCUC CAUGAAGA













3839




CUCAAGUC CUGAUGU X GAA AUCUUCAU




AUGAAGAUA GACUUGAG













3844




CUAUUCUC CUGAUGU X GAA AGUCUAUC




GAUAGACUU GAGAAUAG













3851




UUACUCGC CUGAUGU X GAA AUUCUCAA




UUGAGAAUA GCGAGUAA













3858




CUUGCUUU CUGAUGU X GAA ACUCGCUA




UAGCGAGUA AAAGCAAG













3878




AGAUCGGA CUGAUGU X GAA AGUCCCGC




GCGGGACUU UCCGAUCU













3879




CAGAUCGG CUGAUGU X GAA AAGUCCCG




CGGGACUUU CCGAUCUG













3880




GCAGAUCG CUGAUGU X GAA AAAGUCCC




GGGACUUUC CGAUCUGC













3885




AUCGGAAA CUGAUGU X GAA AUCGGAAA




UUUCCGAUC UGCCGAGG













3901




AGCUGGGC CUGAUGU X GAA AGCUGGGC




GCCCAGCUU CUGCUUCU













3902




AAGCUGGG CUGAUGU X GAA AAGCUGGG




CCCAGCUUC UGCUUCUC













3907




AGCUGGAG CUGAUGU X GAA AGCAGAAG




CUUCUGCUU CUCCAGCU













3908




CAGCUGGA CUGAUGU X GAA AAGCAGAA




UUCUGCUUC UCCAGCUG













3910




CACAGCUG CUGAUGU X GAA AGAAGCAG




CUGCUUCUC CAGCUGUG













3926




ACGGGCCU CUGAUGU X GAA AUGUGGCC




GGCCACAUC AGGCCCGU













3949




CCAGCUCA CUGAUGU X GAA AUUCAUCG




CGAUGAAUC UGAGCUGG













3967




AACAGCAG CUGAUGU X GAA ACUCCUUU




AAAGGAGUC CUGCUGUU













3975




GGGUGGAG CUGAUGU X GAA ACAGCAGG




CCUGCUGUU CUCCACCC













3976




GGGGUGGA CUGAUGU X GAA AACAGCAG




CUGCUGUUC UCCACCCC













3978




UGGGGGUG CUGAUGU X GAA AGAACAGC




GCUGUUCUC CACCCCCA













3991




CGGAGUUG CUGAUGU X GAA AGUCUGGG




CCCAGACUA CAACUCCG













3997




ACACCACG CUGAUGU X GAA AGUUGUAC




CUACAACUC CGUGGUGU













4006




AGGAGUAC CUGAUGU X GAA ACACCACG




CGUGGUGUU GUACUCCU













4009




GGGAGGAG CUGAUGU X GAA ACAACACC




GGUGUUGUA CUCCUCCC













4012




GCGGGGAG CUGAUGU X GAA AGUACAAC




GUUGUACUC CUCCCCGC













4015




CGGGCGGG CUGAUGU X GAA AGGAGUAC




GUACUCCUC CCCGCCCG













4027




AGAAGCUU CUGAUGU X GAA AGGCGGGC




GCCCGCCUA AAGCUUCU













4033




CUGGUGAG CUGAUGU X GAA AGCUUUAG




CUAAAGCUU CUCACCAG













4034




GCUGGUGA CUGAUGU X GAA AAGCUUUA




UAAAGCUUC UCACCAGC













4036




GGGCUGGU CUGAUGU X GAA AGAAGCUU




AAGCUUCUC ACCAGCCC













4066




AUGUAUAA CUGAUGU X GAA ACUGUCAG




CUGACAGUA UUAUACAU













4068




AGAUGUAU CUGAUGU X GAA AUACUGUC




GACAGUAUU AUACAUCU













4069




UAGAUGUA CUGAUGU X GAA AAUACUGU




ACAGUAUUA UACAUCUA













4071




CAUAGAUG CUGAUGU X GAA AUAAUACU




AGUAUUAUA CAUCUAUG













4075




AACUCAUA CUGAUGU X GAA AUGUAUAA




UUAUACAUC UAUGAGUU













4077




UAAACUCA CUGAUGU X GAA AGAUGUAU




AUACAUCUA UGAGUUUA













4083




UAGGUGUA CUGAUGU X GAA ACUCAUAG




CUAUGAGUU UACACCUA













4084




AUAGGUGU CUGAUGU X GAA AACUCAUA




UAUGAGUUU ACACCUAU













4085




AAUAGGUG CUGAUGU X GAA AAACUCAU




AUGUGUUUA CACCUAUU













4091




GAGCGGAA CUGAUGU X GAA AGGUGUAA




UUACACCUA UUCCGCUC













4093




UGGAGCGG CUGAUGU X GAA AUAGGUGU




ACACCUAUU CCGCUCCA













4094




GUGGAGCG CUGAUGU X GAA AAUAGGUG




CACCUAUUC CGCUCCAC













4099




CUCCUGUG CUGAUGU X GAA AGCGGAAU




AUUCCGCUC CACAGGAG













4117




GUCACGAA CUGAUGU X GAA AGCAGCUG




CAGCUGCUU UUCGUGAC













4118




GGUCACGA CUGAUGU X GAA AAGCAGCU




AGCUGCUUU UCGUGACC













4119




AGGUCACG CUGAUGU X GAA AAAGCAGC




GCUGCUUUU CGUGACCU













4120




AAGGUCAC CUGAUGU X GAA AAAAGCAG




CUGCUUUUC GUGACCUU













4128




CACGAUUA CUGAUGU X GAA AGGUCACG




CGUGACCUU UAAUCGUG













4129




GACAGAUU CUGAUGU X GAA AAGGUCAC




GUGACCUUU AAUCGUGC













4130




AGCACGAU CUGAUGU X GAA AAAGGUCA




UGACCUUUA AUCGUGCU













4133




AAAAGCAC CUGAUGU X GAA AUUAAAGG




CCUUUAAUC GUGCUUUU













4139




AAACAAAA CUGAUGU X GAA AGCACGAU




AUCGUGCUU UUUUGUUU













4140




AAAACAAA CUGAUGU X GAA AAGCACGA




UCGUGCUUU UUUGUUUU













4141




AAAAACAA CUGAUGU X GAA AAAGCACG




CGUGCUUUU UUGUUUUU













4142




AAAAAACA CUGAUGU X GAA AAAAGCAC




GUGCUUUUU UGUUUUUU













4143




CAAAAAAC CUGAUGU X GAA AAAAAGCA




UGCUUUUUU GUUUUUUG













4146




AAACAAAA CUGAUGU X GAA ACAAAAAA




UUUUUUGUU UUUUGUUU













4147




AAAACAAA CUGAUGU X GAA AACAAAAA




UUUUUGUUU UUUGUUUU













4148




CAAAACAA CUGAUGU X GAA AAACAAAA




UUUUGUUUU UUGUUUUG













4149




ACAAAACA CUGAUGU X GAA AAAACAAA




UUUGUUUUU UGUUUUGU













4150




AACAAAAC CUGAUGU X GAA AAAAACAA




UUGUUUUUU GUUUUGUU













4153




ACAAACAA CUGAUGU X GAA ACAAAAAA




UUUUUUGUU UUGUUUGU













4154




AACAAACA CUGAUGU X GAA AACAAAAA




UUUUUGUUU UGUUUGUU













4155




CAACAAAC CUGAUGU X GAA AAACAAAA




UUUUGUUUU GUUUGUUG













4158




CAACAACA CUGAUGU X GAA ACAAAACA




UGUUUUGUU UGUUGUUG













4159




GCAACAAC CUGAUGU X GAA AACAAAAC




GUUUUGUUU GUUGUUGC













4162




ACAGCAAC CUGAUGU X GAA ACAAACAA




UUGUUUGUU GUUGCUCU













4165




AAAACAGC CUGAUGU X GAA ACAACAAA




UUUGUUGUU GCUGUUUU













4171




UUAGUCAA CUGAUGU X GAA ACAGCAAC




GUUGCUGUU UUGACUAA













4172




GUUAGUCA CUGAUGU X GAA AACAGCAA




UUGCUGUUU UGACUAAC













4173




UGUUAGUC CUGAUGU X GAA AAACAGCA




UGCUGUUUU GACUAACA













4178




AUUCUUGU CUGAUGU X GAA AGUCAAAA




UUUUGACUA ACAAGAAU













4189




ACUGGGGU CUGAUGU X GAA ACAUUCUU




AAGAAUGUA ACCCCAGU













4198




ACGUCACU CUGAUGU X GAA ACUGGGGU




ACCCCAGUU AGUGACGU













4199




CACGUCAC CUGAUGU X GAA AACUGGGG




CCCCAGUUA GUGACGUG













4216




AACAAUAG CUGAUGU X GAA AUUCUUCA




UGAAGAAUA CUAUUGUU













4219




UCUAACAA CUGAUGU X GAA AGUAUUCU




AGAAUACUA UUGUUAGA













4221




UCUCUAAC CUGAUGU X GAA AUAGUAUU




AAUACUAUU GUUAGAGA













4224




AUUUCUCU CUGAUGU X GAA ACAAUAGU




ACUAUUGUU AGAGAAAU













4225




GAUUUCUC CUGAUGU X GAA AACAAUAG




CUAUUGUUA GAGAAAUC













4233




GCGGGGGG CUGAUGU X GAA AUUUCUCU




AGAGAAAUC CCCCCCGC













4249




GUUACCCU CUGAUGU X GAA AGGCUUUG




CAAAGCCUC AGGGUAAC













4255




GUCCAGGU CUGAUGU X GAA ACCCUGAG




CUCAGGGUA ACCUGGAC













4282




GGUCGCCA CUGAUGU X GAA AGGCACCU




AGGUGCCUC UGGCGACC













4323




GCUGCAGG CUGAUGU X GAA AGGGUGGG




CCCACCCUC CCUGCAGC













4341




ACUGCCUC CUGAUGU X GAA AGUCCCAC




GUGGGACUA GAGGCAGU













4350




AAUGGGCU CUGAUGU X GAA ACUGCCUC




GAGGCAGUA AGCCCAUU













4358




CAUGAGCU CUGAUGU X GAA AUGGGCUU




AAGCCCAUU AGCUCAUG













4359




CCAUGAGC CUGAUGU X GAA AAUGGGCU




AGCCCAUUA GCUCAUGG













4363




GCAGCCAU CUGAUGU X GAA AGCUAAUG




CAUUAGCUC AUGGCUGC













4387




GAGAGACA CUGAUGU X GAA AGCAGGUC




GACCUGCUC UGUCUCUC













4391




AUAAGAGA CUGAUGU X GAA ACAGAGCA




UGCUCUGUC UCUCUUAU













4393




CCAUAAGA CUGAUGU X GAA AGACAGAG




CUCUGUCUC UCUUAUGG













4395




CUCCAUAA CUGAUGU X GAA AGAGACAG




CUGUCUCUC UUAUGGAG













4397




UCCUCCAU CUGAUGU X GAA AGAGAGAC




GUCUCUCUU AUGGAGGA













4398




UUCCUCCA CUGAUGU X GAA AAGAGAGA




UCUCUCUUA UGGAGGAA













4445




GCAUCCCA CUGAUGU X GAA AGCCUUUU




AAAAGGCUU UGGGAUGC













4446




CGCAUCCC CUGAUGU X GAA AAGCCUUU




AAAGGCUUU GGGAUGCG













4456




ACAGGACG CUGAUGU X GAA ACGCAUCC




GGAUGCGUC CGUCCUGU













4460




CUCCACAG CUGAUGU X GAA ACGGACGC




GCGUCCGUC CUGUGGAG













4487




GCAUAGCG CUGAUGU X GAA AGCCCCCU




AGGGGGCUC CGCUAUGC













4492




AAGUGGCA CUGAUGU X GAA AGCGGAGC




GCUCCGCUA UGCCACUU













4500




AGUCACUG CUGAUGU X GAA AGUGGCAU




AUGCCACUU CAGUGACU













4501




AAGUCACU CUGAUGU X GAA AAGUGGCA




UGCCACUUC AGUGACUU













4509




GGAGUGAG CUGAUGU X GAA AGUCACUG




CAGUGACUU CUCACUCC













4510




AGGAGUGA CUGAUGU X GAA AAGUCACU




AGUGACUUC UCACUCCU













4512




CCAGGAGU CUGAUGU X GAA AGAAGUCA




UGACUUCUC ACUCCUGG













4516




GAGGCCAG CUGAUGU X GAA AGUGAGAA




UUCUCACUC CUGGCCUC













4524




AAACAGCG CUGAUGU X GAA AGGCCAGG




CCUGGCCUC CGCUGUUU













4531




GGGCCCGA CUGAUGU X GAA ACAGCGGA




UCCGCUGUU UCGGGCCC













4532




GGGGCCCG CUGAUGU X GAA AACAGCGG




CCGCUGUUU CGGGCCCC













4533




GGGGGCCC CUGAUGU X GAA AAACAGCG




CGCUGUUUC GGGCCCCC













4543




CCUCUUGG CUGAUGU X GAA AGGGGGCC




GGCCCCCUU CCAAGAGG













4544




ACCUCUUG CUGAUGU X GAA AAGGGGGC




GCCCCCUUC CAAGAGGU













4553




UGCUCUGA CUGAUGU X GAA ACCUCUUG




CAAGAGGUA UCAGAGCA













4555




UCUGCUCU CUGAUGU X GAA AUACCUCU




AGAGGUAUC AGAGCAGA













4577




GUCUAGGA CUGAUGU X GAA ACGUCCCU




AGGGACGUU UCCUAGAC













4578




GGUCUAGG CUGAUGU X GAA AACGUCCC




GGGACGUUU CCUAGACC













4579




UGGUCUAG CUGAUGU X GAA AAACGUCC




GGACGUUUC CUAGACCA













4582




CCCUGGUC CUGAUGU X GAA AGGAAACG




CGUUUCCUA GACCAGGG













4598




UUCCCGAG CUGAUGU X GAA ACAUGUGC




GCACAUGUU CUCGGGAA













4599




GUUCCCGA CUGAUGU X GAA AACAUGUG




CACAUGUUC UCGGGAAC













4601




UGGUUCCC CUGAUGU X GAA AGAACAUG




CAUGUUCUC GGGAACCA













4614




UUAAGAUU CUGAUGU X GAA ACUGUGGU




ACCACAGUU AAUCUUAA













4615




UUUAAGAU CUGAUGU X GAA AACUGUGG




CCACAGUUA AUCUUAAA













4618




AGAUUUAA CUGAUGU X GAA AUUAACUG




CAGUUAAUC UUAAAUCU













4620




AAAGAUUU CUGAUGU X GAA AGAUUAAC




GUUAAUCUU AAAUCUUU













4621




AAAAGAUU CUGAUGU X GAA AAGAUUAA




UUAAUCUUA AAUCUUUU













4625




CGGGAAAA CUGAUGU X GAA AUUUAAGA




UCUUAAAUC UUUUCCCG













4627




CCCGGGAA CUGAUGU X GAA AGAUUUAA




UUAAAUCUU UUCCCGGG













4628




UCCCGGGA CUGAUGU X GAA AAGAUUUA




UAAAUCUUU UCCCGGGA













4629




CUCCCGGG CUGAUGU X GAA AAAGAUUU




AAAUCUUUU CCCGGGAG













4630




ACUCCCGG CUGAUGU X GAA AAAAGAUU




AAUCUUUUC CCGGGAGU













4639




CAACAGAA CUGAUGU X GAA ACUCCCGG




CCGGGAGUC UUCUGUUG













4641




GACAACAG CUGAUGU X GAA AGACUCCC




GGGAGUCUU CUGUUGUC













4642




AGACAACA CUGAUGU X GAA AAGACUUC




GGAGUCUUC UGUUGUCU













4646




AAACAGAC CUGAUGU X GAA ACAGAAGA




UCUUCUGUU GUCUGUUU













4649




GGUAAACA CUGAUGU X GAA ACAACAGA




UCUGUUGUC UGUUUACC













4653




GGAUGGUA CUGAUGU X GAA ACAGACAA




UUGUCUGUU UACCAUCC













4654




UGGAUGGU CUGAUGU X GAA AACAGACA




UGUCUGUUU ACCAUCCA













4655




UUGGAUGG CUGAUGU X GAA AAACAGAC




GUCUGUUUA CCAUCCAA













4660




AUGCUUUG CUGAUGU X GAA AUGGUAAA




UUUACCAUC CAAAGCAU













4669




AUGUUAAA CUGAUGU X GAA AUGCUUUG




CAAAGCAUA UUUAACAU













4671




ACAUGUUA CUGAUGU X GAA AUAUGCUU




AAGCAUAUU UAACAUGU













4672




CACAUGUU CUGAUGU X GAA AAUAUGCU




AGCAUAUUU AACAUGUG













4673




ACACAUGU CUGAUGU X GAA AAAUAUGC




GCAUAUUUA ACAUGUGU













4682




CCCCCACU CUGAUGU X GAA ACACAUGU




ACAUGUGUC AGUGGGGG













4698




CAGAAGCC CUGAUGU X GAA AGCGCCAC




GUGGCGCUU GGCUUCUG













4703




GGCCUCAG CUGAUGU X GAA AGCCAAGC




GCUUGGCUU CUGAGGCC













4704




UGGCCUCA CUGAUGU X GAA AACGGAAG




CUUGGCUUC UGAGGCCA













4720




GAACUGAU CUGAUGU X GAA AUGGCUCU




AGAGCCAUC AUCAGUUC













4723




GAGGAACU CUGAUGU X GAA AUGAUGGC




GCCAUCAUC AGUUCCUC













4727




ACUAGAGG CUGAUGU X GAA ACUGAUGA




UCAUCAGUU CCUCUAGU













4728




CACUAGAG CUGAUGU X GAA AACUGAUG




CAUCAGUUC CUCUAGUG













4731




UCUCACUA CUGAUGU X GAA AGGAACUG




CAGUUCCUC UAGUGAGA













4733




CAUCUCAC CUGAUGU X GAA AGAGGAAC




GUUCCUCUA GUGAGAUG













4745




AUGACCUC CUGAUGU X GAA AUGCAUCU




AGAUGCAUU GAGGUCAU













4751




UUGGGUAU CUGAUGU X GAA ACCUCAAU




AUUGAGGUC AUACCCAA













4754




AGCUUGGG CUGAUGU X GAA AUGACCUC




GAGGUCAUA CCCAAGCU













4763




AGGCCUGC CUGAUGU X GAA AGCUUGGG




CCCAAGCUU GCAGGCCU













4777




AGUAUGCG CUGAUGU X GAA AGGUCAGG




CCUGACCUU CGCAUACU













4778




CAGUAUGC CUGAUGU X GAA AAGGUCAG




CUGACCUUC GCAUACUG













4783




GUGAGCAG CUGAUGU X GAA AUGCGAAG




CUUCGCAUA CUGCUCAC













4789




CUCCCCGU CUGAUGU X GAA AGCAGUAU




AUACUGCUC ACGGGGAG













4799




GACCACUU CUGAUGU X GAA ACUCCCCG




CGGGGAGUU AAGUGGUC













4800




GGACCACU CUGAUGU X GAA AACUCCCC




GGGGAGUUA AGUGGUCC













4807




CCAAACUG CUGAUGU X GAA ACCACUUA




UAAGUGGUC CAGUUUGG













4812




CUAGGCCA CUGAUGU X GAA ACUGGACC




GGUCCAGUU UGGCCUAG













4813




ACUAGGCC CUGAUGU X GAA AACUGGAC




GUCCAGUUU GGCCUAGU













4819




AACCUUAC CUGAUGU X GAA AGGCCAAA




UUUGGCCUA GUAAGGUU













4822




GGCAACCU CUGAUGU X GAA ACUAGGCC




GGCCUAGUA AGGUUGCC













4827




CAGUAGGC CUGAUGU X GAA ACCUUACU




AGUAAGGUU GCCUACUG













4832




CCCAUCAG CUGAUGU X GAA AGGCAACC




GGUUGCCUA CUGAUGGG













4843




UGGCUUUU CUGAUGU X GAA AGCCCAUC




GAUGGGCUC AAAAGCCA













4855




CUGUUUAA CUGAUGU X GAA AUGUGGCU




AGCCACAUU UUAAACAG













4856




CCUGUUUA CUGAUGU X GAA AAUGUGGC




GCCACAUUU UAAACAGG













4857




ACCUGUUU CUGAUGU X GAA AAAUGUGG




CCACAUUUU AAACAGGU













4858




AACCUGUU CUGAUGU X GAA AAAAUGUG




CACAUUUUA AACAGGUU













4866




UGAGAUAA CUGAUGU X GAA ACCUGUUU




AAACAGGUU UUAUCUCA













4867




UUGAGAUA CUGAUGU X GAA AACCUGUU




AACAGGUUU UAUCUCAA













4868




CUUGAGAU CUGAUGU X GAA AAACCUGU




ACAGGUUUU AUCUCAAG













4869




ACUUGAGA CUGAUGU X GAA AAAACCUG




CAGGUUUUA UCUCAAGU













4871




AUACUUGA CUGAUGU X GAA AUAAAACC




GGUUUUAUC UCAAGUAU













4873




UAAUACUU CUGAUGU X GAA AGAUAAAA




UUUUAUCUC AAGUAUUA













4878




UAUAUUAA CUGAUGU X GAA ACUUGAGA




UCUCAAGUA UUAAUAUA













4880




UAUAUAUU CUGAUGU X GAA AUACUUGA




UCAAGUAUU AAUAUAUA













4881




CUAUAUAU CUGAUGU X GAA AAUACUUG




CAAGUAUUA AUAUAUAG













4884




UGUCUAUA CUGAUGU X GAA AUUAAUAC




GUAUUAAUA UAUAGACA













4886




CUUGUCUA CUGAUGU X GAA AUAUUAAU




AUUAAUAUA UAGACAAG













4888




GUCUUGUC CUGAUGU X GAA AUAUAUUA




UAAUAUAUA GACAAGAC













4900




UAAUGCAU CUGAUGU X GAA AGUGUCUU




AAGACACUU AUGCAUUA













4901




AUAAUGCA CUGAUGU X GAA AAGUGUCU




AGACACUUA UGCAUUAU













4907




AACAGGAU CUGAUGU X GAA AUGCAUAA




UUAUGCAUU AUCCUGUU













4908




AAACAGGA CUGAUGU X GAA AAUGCAUA




UAUGCAUUA UCCUGUUU













4910




UAAAACAG CUGAUGU X GAA AUAAUGCA




UGCAUUAUC CUGUUUUA













4915




AUAUAUAA CUGAUGU X GAA ACAGGAUA




UAUCCUGUU UUAUAUAU













4916




GAUAUAUA CUGAUGU X GAA AACAGGAU




AUCCUGUUU UAUAUAUC













4917




GGAUAUAU CUGAUGU X GAA AAACAGGA




UCCUGUUUU AUAUAUCC













4918




UGGAUAUA CUGAUGU X GAA AAAACAGG




CCUGUUUUA UAUAUCCA













4920




AUUGGAUA CUGAUGU X GAA AUAAAACA




UGUUUUAUA UAUCCAAU













4922




UCAUUGGA CUGAUGU X GAA AUAUAAAA




UUUUAUAUA UCCAAUGA













4924




AUUCAUUG CUGAUGU X GAA AUAUAUAA




UUAUAUAUC CAAUGAAU













4933




CCCAGUUA CUGAUGU X GAA AUUCAUUG




CAAUGAAUA UAACUGGG













4935




GCCCCAGU CUGAUGU X GAA AUAUUCAU




AUGAAUAUA ACUGGGGC













4948




UGACUCUU CUGAUGU X GAA ACUCGCCC




GGGCGAGUU AAGAGUCA













4949




AUGACUCU CUGAUGU X GAA AACUCGCC




GGCGAGUUA AGAGUCAU













4955




UAGACCAU CUGAUGU X GAA ACUCUUAA




UUAAGAGUC AUGGUCUA













4961




CUUUUCUA CUGAUGU X GAA ACCAUGAC




GUCAUGGUC UAGAAAAG













4963




CCCUUUUC CUGAUGU X GAA AGACCAUG




CAUGGUCUA GAAAAGGG













4974




UACAGAGA CUGAUGU X GAA ACCCCUUU




AAAGGGGUU UCUCUGUA













4975




GUACAGAG CUGAUGU X GAA AACCCCUU




AAGGGGUUU CUCUGUAC













4976




GGUACAGA CUGAUGU X GAA AAACCCCU




AGGGGUUUC UCUGUACC













4978




UGGGUACA CUGAUGU X GAA AGAAACCC




GGGUUUCUC UGUACCCA













4982




GAUUUGGG CUGAUGU X GAA ACAGAGAA




UUCUCUGUA CCCAAAUC













4990




ACCAGCCC CUGAUGU X GAA AUUUGGGU




ACCCAAAUC GGGCUGGU













4999




CUUGGUCC CUGAUGU X GAA ACCAGCCC




GGGCUGGUU GGACCAAG













5029




GCUGGGAC CUGAUGU X GAA ACCACUCU




AGAGUGGUU GUCCCAGC













5032




AUAGCUGG CUGAUGU X GAA ACAACCAC




GUGGUUGUC CCAGCUAU













5039




AGUAACUA CUGAUGU X GAA AGCUGGGA




UCCCAGCUA UAGUUACU













5041




UUAGUAAC CUGAUGU X GAA AUAGCUGG




CCAGCUAUA GUUACUAA













5044




AGUUUAGU CUGAUGU X GAA ACUAUAGC




GCUAUAGUU ACUAAACU













5045




UAGUUUAG CUGAUGU X GAA AACUAUAG




CUAUAGUUA CUAAACUA













5048




GAGUAGUU CUGAUGU X GAA AGUAACUA




UAGUUACUA AACUACUC













5053




UGGGUGAG CUGAUGU X GAA AGUUUAGU




ACUAAACUA CUCACCCA













5056




CUUUGGGU CUGAUGU X GAA AGUAGUUU




AAACUACUC ACCCAAAG













5066




GAGGUCCC CUGAUGU X GAA ACUUUGGG




CCCAAAGUU GGGACCUC













5074




AAGCCAGU CUGAUGU X GAA AGGUCCCA




UGGGACCUC ACUGGCUU













5082




GUAAAGAG CUGAUGU X GAA AGCCAGUG




CACUGGCUU CUCUUUAC













5083




AGUAAAGA CUGAUGU X GAA AAGCCAGU




ACUGGCUUC UCUUUACU













5085




GAAGUAAA CUGAUGU X GAA AGAAGCCA




UGGCUUCUC UUUACUUC













5087




AUGAAGUA CUGAUGU X GAA AGAGAAGC




GCUUCUCUU UACUUCAU













5088




GAUGAAGU CUGAUGU X GAA AAGAGAAG




CUUCUCUUU ACUUCAUC













5089




UGAUGAAG CUGAUGU X GAA AAAGAGAA




UUCUCUUUA CUUCAUCA













5092




CCAUGAUG CUGAUGU X GAA AGUAAAGA




UCUUUACUU CAUCAUGG













5093




UCCAUGAU CUGAUGU X GAA AAGUAAAG




CUUUACUUC AUCAUGGA













5096




AAAUCCAU CUGAUGU X GAA AUGAAGUA




UACUUCAUC AUGGAUUU













5103




GAUGGUGA CUGAUGU X GAA AUCCAUGA




UCAUGGAUU UCACCAUC













5104




GGAUGGUG CUGAUGU X GAA AAUCCAUG




CAUGGAUUU CACCAUCC













5105




GGGAUGGU CUGAUGU X GAA AAAUCCAU




AUGGAUUUC ACCAUCCC













5111




UGCCUUGG CUGAUGU X GAA AUGGUGAA




UUCACCAUC CCAAGGCA













5122




UCCUCUCA CUGAUGU X GAA ACUGCCUU




AAGGCAGUC UGAGAGGA













5134




AUACUCUU CUGAUGU X GAA AGCUCCUC




GAGGAGCUA AAGAGUAU













5141




UGGGCUGA CUGAUGU X GAA ACUCUUUA




UAAAGAGUA UCAGCCCA













5143




UAUGGGCU CUGAUGU X GAA AUACUCUU




AAGAGUAUC AGCCCAUA













5151




UUAAUAAA CUGAUGU X GAA AUGGGCUG




CAGCCCAUA UUUAUUAA













5153




GCUUAAUA CUGAUGU X GAA AUAUGGGC




GCCCAUAUU UAUUAAGC













5154




UGCUUAAU CUGAUGU X GAA AAUAUGGG




CCCAUAUUU AUUAAGCA













5155




GUGCUUAA CUGAUGU X GAA AAAUAUGG




CCAUAUUUA UUAAGCAC













5157




AAGUGCUU CUGAUGU X GAA AUAAAUAU




AUAUUUAUU AAGCACUU













5158




AAAGUGCU CUGAUGU X GAA AAUAAAUA




UAUUUAUUA AGCACUUU













5165




GGAGCAUA CUGAUGU X GAA AGUGCUUA




UAAGCACUU UAUGCUCC













5166




AGGAGCAU CUGAUGU X GAA AAGUGCUU




AAGCACUUU AUGCUCCU













5167




AAGGAGCA CUGAUGU X GAA AAAGUGCU




AGCACUUUA UGCUCCUU













5172




GUGCCAAG CUGAUGU X GAA AGCAUAAA




UUUAUGCUC CUUGGCAC













5175




GCUGUGCC CUGAUGU X GAA AGGAGCAU




AUGCUCCUU GGCACAGC













5195




GCAUAAAU CUGAUGU X GAA ACACAUCA




UGAUGUGUA AUUUAUGC













5198




CUUGCAUA CUGAUGU X GAA AUUACACA




UGUGUAAUU UAUGCAAG













5199




GCUUGCAU CUGAUGU X GAA AAUUACAC




GUGUAAUUU AUGCUUGC













5200




AGCUUGCA CUGAUGU X GAA AAAUUACA




UGUAAUUUA UGCAAGCU













5209




UGGAGAGG CUGAUGU X GAA AGCUUGCA




UGCAAGCUC CCUCUCCA













5213




UAGCUGGA CUGAUGU X GAA AGGGAGCU




AGCUCCCUC UCCAGCUA













5215




CCUAGCUG CUGAUGU X GAA AGAGGGAG




CUCCCUCUC CAGCUAGG













5221




CUGAGUCC CUGAUGU X GAA AGCUGGAG




CUCCAGCUA GGACUCAG













5227




AAUAUCCU CUGAUGU X GAA AGUCCUAG




CUAGGACUC AGGAUAUU













5233




UUGACUAA CUGAUGU X GAA AUCCUGAG




CUCAGGAUA UUAGUCAA













5235




CAUUGACU CUGAUGU X GAA AUAUCCUG




CAGGAUAUU AGUCAAUG













5236




UCAUUGAC CUGAUGU X GAA AAUAUCCU




AGGAUAUUA GUCAAUGA













5239




GGCUCAUU CUGAUGU X GAA ACUAAUAU




AUAUUAGUC AAUGAGCC













5250




UUCCUUUU CUGAUGU X GAA AUGGCUCA




UGAGCCAUC AAAAGGAA













5273




AAAUAAGA CUGAUGU X GAA AGGUUUUU




AAAAACCUA UCUUAUUU













5275




GAAAAUAA CUGAUGU X GAA AUAGGUUU




AAACCUAUC UUAUUUUC













5277




AUGAAAAU CUGAUGU X GAA AGAUAGGU




ACCUAUCUU AUUUUCAU













5278




GAUGAAAA CUGAUGU X GAA AAGAUAGG




CCUAUCUUA UUUUCAUC













5280




CAGAUGAA CUGAUGU X GAA AUAAGAUA




UAUCUUAUU UUCAUCUG













5281




ACAGAUGA CUGAUGU X GAA AAUAAGAU




AUCUUAUUU UCAUCUGU













5282




AACAGAUG CUGAUGU X GAA AAAUAAGA




UCUUAUUUU CAUCUGUU













5283




AAACAGAU CUGAUGU X GAA AAAAUAAG




CUUAUUUUC AUCUGUUU













5286




AUGAAACA CUGAUGU X GAA AUGAAAAU




AUUUUCAUC UGUUUCAU













5290




AGGUAUGA CUGAUGU X GAA ACAGAUGA




UCAUCUGUU UCAUACCU













5291




AAGGUAUG CUGAUGU X GAA AACAGAUG




CAUCUGUUU CAUACCUU













5292




CAAGGUAU CUGAUGU X GAA AAACAGAU




AUCUGUUUC AUACCUUG













5295




AGACAAGG CUGAUGU X GAA AUGAAACA




UGUUUCAUA CCUUGUCU













5299




CCCCAGAC CUGAUGU X GAA AGGUAUGA




UCAUACCUU GUCUGGGG













5302




AGACCCCA CUGAUGU X GAA ACAAGGUA




UACCUUGUC UGGGGUCU













5309




CGUCAUUA CUGAUGU X GAA ACCCCAGA




UCUGGGGUC UAAUGACG













5311




AUCGUCAU CUGAUGU X GAA AGACCCCA




UGGGGUCUA AUGACGAU













5331




CCCAUGUC CUGAUGU X GAA ACCCUGUU




AACAGGGUA GACAUGGG













5350




CCCUUUUC CUGAUGU X GAA ACCCUGUC




GACAGGGUA GAAAAGGG













5367




ACCCCAAA CUGAUGU X GAA AGCGGGCA




UGCCCGCUC UUUGGGGU













5369




AGACCCCA CUGAUGU X GAA AGAGCGGG




CCCGCUCUU UGGGGUCU













5370




UAGACCCC CUGAUGU X GAA AAGAGCGG




CCGCUCUUU GGGGUCUA













5376




CAUCUCUA CUGAUGU X GAA ACCCCAAA




UUUGGGGUC UAGAGAUG













5378




CUCAUCUC CUGAUGU X GAA AGACCCCA




UGGGGUCUA GAGAUGAG













5395




AUUUUAGA CUGAUGU X GAA ACCCAGGG




CCCUGGGUC UCUAAAAU













5397




CCAUUUUA CUGAUGU X GAA AGACCCAG




CUGGGUCUC UAAAAUGG













5399




AGCCAUUU CUGAUGU X GAA AGAGACCC




GGGUCUCUA AAAUGGCU













5408




UUCUAAGA CUGAUGU X GAA AGCCAUUU




AAAUGGCUC UCUUAGAA













5410




ACUUCUAA CUGAUGU X GAA AGAGCCAU




AUGGCUCUC UUAGAAGU













5412




CAACUUCU CUGAUGU X GAA AGAGAGCC




GGCUCUCUU AGAAGUUG













5413




ACAACUUC CUGAUGU X GAA AAGUGUGC




GCUCUCUUA GAAGUUGU













5419




GCACAUAC CUGAUGU X GAA ACUUCUAA




UUAGAAGUU GUAUGUGC













5422




UUUGCACA CUGAUGU X GAA ACAACUUC




GAAGUUGUA UGUGCAAA













5432




CAGACCAU CUGAUGU X GAA AUUUGCAC




GUGCAAAUU AUGGUCUG













5433




ACAGACCA CUGAUGU X GAA AAUUUGCA




UGCAAAUUA UGGUCUGU













5438




AGCACACA CUGAUGU X GAA ACCAUAAU




AUUAUGGUC UGUGUGCU













5447




CACGACCU CUGAUGU X GAA AGCACACA




UGUGUGCUU AGGUCGUG













5448




GCACGACC CUGAUGU X GAA AAGCACAC




GUGUGCUUA GGUCGUGC













5452




GUGUGCAC CUGAUGU X GAA ACCUAAGC




GCUUAGGUC GUGCACAC













5475




CCAGCUGU CUGAUGU X GAA ACCGGCUC




GAGCCGGUC ACAGCUGG













5497




AAAGCAGC CUGAUGU X GAA AUUCAUCG




CGAUGAAUA GCUGCUUU













5504




CUCUCCCA CUGAUGU X GAA AGCAGCUA




UAGCUGCUU UGGGAGAG













5505




GCUCUCCC CUGAUGU X GAA AAGCAGCU




AGCUGCUUU GGGAGAGC













5524




UAAGUGGC CUGAUGU X GAA AGCAUGCU




AGCAUGCUA GCCACUUA













5531




AGAGAAUU CUGAUGU X GAA AGUGGCUA




UAGCCACUU AAUUCUCU













5532




CAGAGAAU CUGAUGU X GAA AAGUGGCU




AGCCACUUA AUUCUCUG













5535




GCUCAGAG CUGAUGU X GAA AUUAAGUG




CACUUAAUU CUCUGACC













5536




CGGUCAGA CUGAUGU X GAA AAUUAAGU




ACUUAAUUC UCUGACCG













5538




CCCGGUCA CUGAUGU X GAA AGAAUUAA




UUAAUUCUC UGACCGGG













5554




GUACCCAU CUGAUGU X GAA AUGCUGGC




GCCAGCAUC AUGGGUAC













5561




GGAGCAGG CUGAUGU X GAA ACCCAUGA




UCAUGGGUA CCUGCUCC













5568




ACACAGGG CUGAUGU X GAA AGCAGGUA




UACCUGCUC CCCUGUGU













5577




GGAUGGGG CUGAUGU X GAA ACACAGGG




CCCUGUGUA CCCCAUCC













5584




ACCUUAAG CUGAUGU X GAA AUGGGGUA




UACCCCAUC CUUAAGGU













5587




AAAACCUU CUGAUGU X GAA AGGAUGGG




CCCAUCCUU AAGGUUUU













5588




GAAAACCU CUGAUGU X GAA AAGGAUGG




CCAUCCUUA AGGUUUUC













5593




AGACAGAA CUGAUGU X GAA ACCUUAAG




CUUAAGGUU UUCUGUCU













5594




CAGACAGA CUGAUGU X GAA AACCUUAA




UUAAGGUUU UCUGUCUG













5595




UCAGACAG CUGAUGU X GAA AAACCUUA




UAAGGUUUU CUGUCUGA













5596




AUCAGACA CUGAUGU X GAA AAAACCUU




AAGGUUUUC UGUCUGAU













5600




UCUCAUCA CUGAUGU X GAA ACAGAAAA




UUUUCUGUC UGAUGAGA













5627




UCAGUGGG CUGAUGU X GAA AUUGCACU




AGUGCAAUC CCCACUGA













5660




UGCACCAA CUGAUGU X GAA AGCCACAG




CUGUGGCUC UUGGUGCA













5662




AGUGCACC CUGAUGU X GAA AGAGCCAC




GUGGCUCUU GGUGCACU













5671




UGGCUGGU CUGAUGU X GAA AGUGCACC




GGUGCACUC ACCAGCCA













5685




UACUUGUC CUGAUGU X GAA AGUCCUGG




CCAGGACUA GACAAGUA













5693




CCCUUUCC CUGAUGU X GAA ACUUGUCU




AGACAAGUA GGAAAGGG













5704




GUGGCUAG CUGAUGU X GAA AGCCCUUU




AAAGGGCUU CUAGCCAC













5705




UGUGGCUA CUGAUGU X GAA AAGCCCUU




AAGGGCUUC UAGCCACA













5707




AGUGUGGC CUGAUGU X GAA AGAAGCCC




GGGCUUCUA GCCACACU













5731




CCCUACCU CUGAUGU X GAA AUUUUCUU




AAGAAAAUC AGGUAGGG













5736




GCCAGCCC CUGAUGU X GAA ACCUGAUU




AAUCAGGUA GGGCUGGC













5754




UGGACAAA CUGAUGU X GAA AUGUCUUU




AAAGACAUC UUUGUCCA













5756




AAUGGACA CUGAUGU X GAA AGAUGUCU




AGACAUCUU UGUCCAUU













5757




GAAUGGAC CUGAUGU X GAA AAGAUGUC




GACAUCUUU GUCCAUUC













5760




UGCGAAUG CUGAUGU X GAA ACAAAGAU




AUCUUUGUC CAUUCGCA













5764




CUUUUGCG CUGAUGU X GAA AUGGACAA




UUGUCCAUU CGCAAAAG













5765




GCUUUUGC CUGAUGU X GAA AAUGGACA




UGUCCAUUC GCAAAAGC













5775




GCCGACAA CUGAUGU X GAA AGCUUUUG




CAAAAGCUC UUGUCGGC













5777




CAGCCGAC CUGAUGU X GAA AGAGCUUU




AAAGCUCUU GUCGGCUG













5780




CUGCAGCC CUGAUGU X GAA ACAAGAGC




GCUGUUGUC GGCUGCAG













5794




GCCUGACU CUGAUGU X GAA ACACACUG




CAGUGUGUA AGUCAGGC













5798




CAUCGCCU CUGAUGU X GAA ACUUACAC




GUGUAAGUC AGGCGAUG













5818




UUCUCUGG CUGAUGU X GAA AGCCUGUC




CAGAGGCUA CCAGAGAA













5852




GGAUGAGA CUGAUGU X GAA ACCUCAGG




CCUGAGGUU UCUCAUCC













5853




UGGAUGAG CUGAUGU X GAA AACCUCAG




CUGAGGUUU CUCAUCCA













5854




CUGGAUGA CUGAUGU X GAA AAACCUCA




UGAGGUUUC UCAUCCAG













5856




AUCUGGAU CUGAUGU X GAA AGAAACCU




AGGUUUCUC AUCCAGAU













5859




GAUAUCUG CUGAUGU X GAA AUGAGAAA




UUUCUCAUC CAGAUAUC













5865




UUGCUGGA CUGAUGU X GAA AUCUGGAU




AUCCAGAUA UCCAGCAA













5867




AAUUGCUG CUGAUGU X GAA AUAUCUGG




CCAGAUAUC CAGCAAUU













5875




CACCCCCC CUGAUGU X GAA AUUGCUGG




CCAGCAAUU GGGGGGUG













5896




GGACCAUC CUGAUGU X GAA AUGGUCUU




AAGACCAUA GAUGGUCC













5903




UAAUACAG CUGAUGU X GAA ACCAUCUA




UAGAUGGUC CUGUAUUA













5908




AGGAAUAA CUGAUGU X GAA ACAGGACC




GGUCCUGUA UUAUUCCG













5910




AUCGGAAU CUGAUGU X GAA AUACAGGA




UCCUGUAUU AUUCCGAU













5911




AAUCGGAA CUGAUGU X GAA AAUACAGG




CCUGUAUUA UUCCGAUU













5913




AAAAUCGG CUGAUGU X GAA AUAAUACA




UGUAUUAUU CCGAUUUU













5914




UAAAAUCG CUGAUGU X GAA AAUAAUAC




GUAUUAUUC CGAUUUUA













5919




AUUAUUAA CUGAUGU X GAA AUCGGAAU




AUUCCGAUU UUAAUAAU













5920




GAUUAUUA CUGAUGU X GAA AAUCGGAA




UUCCGAUUU UAAUAAUC













5921




AGAUUAUU CUGAUGU X GAA AAAUCGGA




UCCGAUUUU AAUAAUCU













5922




UAGAUUAU CUGAUGU X GAA AAAAUCGG




CCGAUUUUA AUAAUCUA













5925




AAUUAGAU CUGAUGU X GAA AUUAAAAU




AUUUUAAUA AUCUAAUU













5928




ACGAAUUA CUGAUGU X GAA AUUAUUAA




UUAAUAAUC UAAUUCGU













5930




UCACGAAU CUGAUGU X GAA AGAUUAUU




AAUAAUCUA AUUCGUGA













5933




UGAUCACG CUGAUGU X GAA AUUAGAUU




AAUCUAAUU CGUGAUCA













5934




AUGAUCAC CUGAUGU X GAA AAUUAGAU




AUCUAAUUC GUGAUCAU













5940




CUCUUAAU CUGAUGU X GAA AUCACGAA




UUCGUGAUC AUUAAGAG













5943




AGUCUCUU CUGAUGU X GAA AUGAUCAC




GUGAUCAUU AAGAGACU













5944




AAGUCUCU CUGAUGU X GAA AAUGAUCA




UGAUCAUUA AGAGACUU













5952




AUUUACUA CUGAUGU X GAA AGUCUCUU




AAGAGACUU UAGUAAAU













5953




CAUUUACU CUGAUGU X GAA AAGUCUCU




AGAGACUUU AGUAAAUG













5954




ACAUUUAC CUGAUGU X GAA AAAGUCUC




GAGACUUUA GUAAAUGU













5957




GGGACAUU CUGAUGU X GAA ACUAAAGU




ACUUUAGUA AAUGUCCC













5963




GGAAAAGG CUGAUGU X GAA ACAUUUAC




GUAAAUGUC CCUUUUCC













5967




UGUGGGAA CUGAUGU X GAA AGGGACAU




AUGUCCCUU UUCCCACA













5968




UUGUGGGA CUGAUGU X GAA AAGGGACA




UGUCCCUUU UCCCACAA













5969




UUUGUGGG CUGAUGU X GAA AAAGGGAC




GUCCCUUUU CCCACAAA













5970




UUUUGUGG CUGAUGU X GAA AAAAGGGA




UCCCUUUUC CCACAAAA













5981




CUUUUCUU CUGAUGU X GAA ACUUUUGU




ACAAAAGUA AAGAAAAG













5992




AAUCCCGA CUGAUGU X GAA AGCUUUUC




GAAAAGCUA UCGGGAUU













5994




AGAAUCCC CUGAUGU X GAA AUAGCUUU




AAAGCUAUC GGGAUUCU













6000




AACCAGAG CUGAUGU X GAA AUCCCGAU




AUCGGGAUU CUCUGGUU













6001




GAACCAGA CUGAUGU X GAA AAUCCCGA




UCGGGAUUC UCUGGUUC













6003




CAGAACCA CUGAUGU X GAA AGAAUCCC




GGGAUUCUC UGGUUCUG













6008




UUAAGCAG CUGAUGU X GAA ACCAGAGA




UCUCUGGUU CUGCUUAA













6009




UUUAAGCA CUGAUGU X GAA AACCAGAG




CUCUGGUUC UGCUUAAA













6014




AAGUCUUU CUGAUGU X GAA AGCAGAAC




GUUCUGCUU AAAGACUU













6015




UAAGUCUU CUGAUGU X GAA AAGCAGAA




UUCUGCUUA AAGACUUA













6022




CCAAAGCU CUGAUGU X GAA AGUCUUUA




UAAAGACUU AGCUUUGG













6023




UCCAAAGC CUGAUGU X GAA AAGUCUUU




AAAGACUUA GCUUUGGA













6027




AGGCUCCA CUGAUGU X GAA AGCUAAGU




ACUUAGCUU UGGAGCCU













6028




UAGGCUCC CUGAUGU X GAA AAGCUAAG




CUUAGCUUU GGAGCCUA













6036




AACUUUCA CUGAUGU X GAA AGGCUCCA




UGGAGCCUA UGAAAGUU













6044




GGCUGAUC CUGAUGU X GAA ACUUUCAU




AUGAAAGUU GAUCAGCC











Where “X” represents stem II region of a HH ribozyme (Hertel et al., 1992 Nucleic Acids Res. 20 3252). The length of stem II may be ≧ 2 base-pairs.





















TABLE IX











Mouse flt1 VEGF Receptor-Hairpin Ribozyme and Substrate Sequence













nt.








Position




HP Ribozyme




Substrate









  33




GUCCCAGC AGAA GACCAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUGGUCA GCU GCUGGGAC













  36




GGUGUCCC AGAA CCUGAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUCAGCU GCU GGGACACC













  50




UAAGGCAA AGAA GCGGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACCGCG GUC UUGCCUUA













  67




GACACCCG AGAA GCGCGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACGCGCU GCU CGGGUGUC













  79




CUGUGAGA AGAA GACACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGUCUCU GCU UCUCACAG













 166




GAAAGAGA AGAA GGCCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAGGCCA GAC UCUCUUUC













 197




CAUGAGUG AGAA GCCUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAGGCA GCC CACUCAUG













 214




CGGUCGUG AGAA GAGACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGUCUCU GCC CACGACCG













 266




CUCCCACA AGAA GAUGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCCAUCG GCC UGUGGGAG













 487




GGAUGAUG AGAA GUCUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAAGACA GCU CAUCAUCC













 501




CGUCACCC AGAA GGGGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUCCCCU GCC GGGUGACG













 566




CUUUGCCC AGAA GGGGUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UACCCCU GAU GGGCAAAG













 640




CGCAGUUC AGAA GUCCUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UAGGACU GCU GAACUGCG













 691




GCCGAUGG AGAA GAUAGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACUAUCU GAC CCAUCGGC













 703




UUGUAUUG AGAA GCCGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUCGGCA GAC CAAUACAA













 736




CUGGGCUC AGAA GGCGUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UACGCCC GCC GAGCCCAG













 754




GCCCGUGG AGAA GUCUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAGACU GCU CCACGGGC













 766




GGACAAGA AGAA GCCCGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACGGGCA GAC UCUUGUCC













 871




UCCGGUCA AGAA GCUGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCAGCG GAU UGACCGGA













 960




CUUCACGC AGAA GGUGUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UACACCU GUC GCGUGAAG













 988




UGUUGAAA AGAA GGAACG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CGUUCCA GUC UUUCAACA













1051




CCUGCACC AGAA GCUUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAAGCA GCC GGUGCAGG













1081




GCCGAUAG AGAA GUCUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAAGACG GUC CUAUCGGC













1090




UCAUGGAC AGAA GAUAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUAUCG GCU GUCCAUGA













1093




CUUUCAUG AGAA GCCGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUCGGCU GUC CAUGAAAG













1169




AAAUAGCG AGAA GACUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAAGUCU GCU CGCUAUUU













1315




UUUCGUAG AGAA GAGGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AACCUCA GAU CUACGAAA













1363




UGCUGCCC AGAA GAUAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUAUCC GCU GGGCAGCA













1604




GUCUGAGA AGAA GCCACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGUGGCU GAC UCUCAGAC













1612




UUCCAGGG AGAA GAGAGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACUCUCA GAC CCCUGGAA













1629




GGCCCGGC AGAA GUAGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUCUACA GCU GCCGGGCC













1632




GAAGGCCC AGAA GCUGUA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UACAGCU GCC GGGCCUUC













1688




UUCGGCAC AGAA GUGACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUCACA GAU GUGCCGAA













1730




UCUCCUUC AGAA GGCAUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAUGCCA GCC GAAGGAGA













1753




CCACACAG AGAA GUUUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAAACU GUC CUGUGUGG













2017




GGuUUUGA AGAA GGUGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACACCU GCU UCAAAACC













2101




ACCAAGUG AGAA GAGGCG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CGCCUCA GAU CACUUGGU













2176




UUUCAAUA AGAA GCGUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCACGCU GUU UAUUGAAA













2258




GUGAGGUA AGAA GCGCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGCGCA GCC UACCUCAC













2305




UGAGCGUG AGAA GCUCCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGAGCU GAU CACGCUCA













2383




CGGAAGAA AGAA GCUUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAAGCG GUC UUCUUCCG













2405




GACAGGUA AGAA GUCUUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAAGACA GAC UACCUGUC













2432




GGAACUUC AGAA GGGUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGACCCA GAU GAAGUUCC













2464




CAUAGGGC AGAA GUUCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUGAACG GCU GCCCUAUG













2467




CAUCAUAG AGAA GCCGUU ACCAGAGAAACACACCUUGUGGUACAUUACCUGGUA




AACGGCU GCC CUAUGAUG













2592




CACAGUCC AGAA GGUGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCCACCU GCC GGACUGUG













2596




CAGCCACA AGAA GGCAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUGCCG GAC UGUGGGUG













2653




GUUCGGUC AGAA GAGCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGCUCU GAU GACCGAAC













2743




CGAUCACC AGAA GAGGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCCUCU GAU GGUGAUCG













2779




GGUAGUUG AGAA GGUUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAAACCU GUC CAACUACC













2814




CUUGUUGA AGAA GAAUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUAUUCU GUC UCAACAAG













2831




AUAUGCAA AGAA GCGUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGACGCA GCC UUGCAUAU













2895




ACUGUCUA AGAA GGGCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGCCCC GCC UAGACAGU













2913




GACACUUG AGAA GCUGAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUCAGCA GCU CAAGUGUC













2928




GAAGCUGG AGAA GGUGAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUCACCA GCU CCAGCUUC













2934




UUCAGGGA AGAA GGAGCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGCUCCA GCU UCCCUGAA













3001




UGGUGAGG AGAA GCUUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCAAGCA GCC CCUCACCA













3022




UGUAGGAA AGAA GGUCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGACCU GAU UUCCUACA













3033




CACUUGGA AGAA GUAGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCCUACA GUU UCCAAGUG













3064




UUCUGGAG AGAA GAAACU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGUUUCU GUC CUCCAGAA













3179




CUCACAUA AGAA GGGUUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAACCCU GAU UAUGUGAG













3357




CUUCAGGC AGAA GCAGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUCUGCA GCC GCCUGAAG













3360




UUCCUUCA AGAA GCUGCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGCAGCC GCC UGAAGGAA













3379




GGGUUCUC AGAA GCAUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCAUGCG GAU GAGAACCC













3463




GUUCAGCA AGAA GGGGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCCCCG GUU UGCUGAAC













3496




UGGCUUGA AGAA GGUCAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUGACCU GCU UCAAGCCA













3553




UGUUUCUA AGAA GUAUGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCAUACU GAC UAGAAACA













3615




AUCUGCAA AGAA GUCCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGGACG GCU UUGCAGAU













3623




AAAUGUGG AGAA GCAAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUUGCA GAU CCACAUUU













3650




CUCACAUC AGAA GAGCUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAGCUCU GAU GAUGUGAG













3754




UAGUGUCC AGAA GAUAGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACUAUCA GCU GGACACUA













3772




GGGAGCCC AGAA GAGUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCACUCU GCU GGGCUCCC













3796




UCCAGGUG AGAA GCUUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAAGCG GUU CACCUGGA













3881




CUCGGCAG AGAA GAAAGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACUUUCC GAU CUGCCGAG













3886




UGGGCCUC AGAA GAUCGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCGAUCU GCC GAGGCCCA













3897




GAAGCAGA AGAA GGGCCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGGCCCA GCU UCUGCUUC













3903




GCUGGAGA AGAA GAAGCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGCUUCU GCU UCUCCAGC













3912




GUGGCCAC AGAA GGAGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUCUCCA GCU GUGGCCAC













3969




UGGAGAAC AGAA GGACUC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GAGUCCU GCU GUUCUCCA













3972




GGGUGGAG AGAA GCAGGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCCUGCU GUU CUCCACCC













3986




GAGUUGUA AGAA GGGGGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACCCCCA GAC UACAACUC













4018




UUUAGGCG AGAA GGGAGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCUCCCC GCC CGCCUAAA













4022




AAGCUUUA AGAA GGCGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCCGCCC GCC UAAAGCCU













4040




GUUGUCGG AGAA GGUGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCACCA GCC CCGACAAC













4053




CUGUCAGG AGAA GGUUGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACAACCA GCC CCUGACAG













4095




UCCUGUGG AGAA GAAUAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUAUUCC GCU CCACAGGA













4110




CGAAAAGC AGAA GGCUCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGAGCCA GCU GCUUUUCG













4113




UCACGAAA AGAA GCUGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCCAGCU GGU UUUCGUGA













4168




UUAGUCAA AGAA GCAACA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGUUGCU GUU UUGACUAA













4290




GGUGGGCG AGAA GUCGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CGCGACC GCC CGCCCACC













4294




GGCCGGUG AGAA GGCGGU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




ACCGCCC GCC CACCGGCC













4329




AGUCCCAC AGAA GCAGGG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CCCUGCA GCU GUGGGACU













4378




CAGAGCAG AGAA GUGCAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUGCACU GAC CUGCUCUG













4383




AGAGACAG AGAA GGUCAG ACCAGAGAAACACACCUUGUGGUACAUUACCUGGUA




CUGACCU GCU CUGUCUCU













4388




AUAAGAGA AGAA GAGCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGCUCU GUC UCUCUUAU













4457




CUCCACAG AGAA GACGCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGCGUCC GUC CUGUGGAG













4525




CCCGAAAC AGAA GACGCC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGCCUCC GCU GUUUCGGG













4528




GGGCCCGA AGAA GCGGAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUCCGCU GUU UCGGGCCC













4643




AAACAGAC AGAA GAAGAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUCUUCU GUU GUCUGUUU













4650




GGAUGGUA AGAA GACAAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUUGUCU GUU UACCAUCC













4724




ACUAGAGG AGAA GAUGAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUCAUCA GUU CCUCUAGU













4771




AUGCGAAG AGAA GGCCUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAGGCCU GAC CUUCGCAU













4785




UCCCCGUG AGAA GUAUGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCAUACU GCU CACGGGGA













4809




CUAGGCCA AGAA GGACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGUCCA GUU UGGCCUAG













4834




UUGAGCCC AGAA GUAGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCCUACU GAU GGGCUCAA













4912




AUAUAUAA AGAA GGAUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUAUCCU GUU UUAUAUAU













5119




UCCUCUCA AGAA GCCUUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CAAGGCA GUC UGAGAGGA













5144




UAAAUAUG AGAA GAUACU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGUAUCA GCC CAUAUUUA













5287




AGGUAUGA AGAA GAUGAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUCAUCU GUU UCAUACCU













5363




CCCCAAAG AGAA GGCACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGUGCCC GCU CUUUGGGG













5462




CCGGCUCC AGAA GGUGUG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CACACCU GCC GGAGCCGG













5478




GUCUGCCC AGAA GUGACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGUCACA GCU CGGCAGAC













5486




UAUUCAUC AGAA GCCCAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUGGGCA GAC GAUGAAUA













5500




UCUCCCAA AGAA GCUAUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AAUAGCU GCU UUGGGAGA













5539




CUGGCCCG AGAA GAGAAU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AUUCUCU GAC CGGGCCAG













5564




CACAGGGG AGAA GGUACC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GGUACCU GCU CCCCUGUG













5597




UCUCAUCA AGAA GAAAAC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GUUUUCU GUC UGAUGAGA













5601




CCAGUCUC AGAA GACAGA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UCUGUCU GAU GAGACUGG













5639




GGGCUGCA AGAA GUCUCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGAGACA GCC UGCAGCCC













5646




CCACAGUG AGAA GCAGGC ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




GCCUGCA GCC CACUGUGG













5781




CACACUGC AGAA GACAAG ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




CUUGUCG GCU GCAGUGUG













5829




CUGUUCUC AGAA GUUUCU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AGAAACG GAU GAGAACAG













5842




AAACCUCA AGAA GCUGUU ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




AACAGCA GCC UGAGGUUU













5915




UUAUUAAA AGAA GAAUAA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UUAUUCC GAU UUUAAUAA













6010




AGUCUUUA AGAA GAACCA ACCAGAGAAACACACGUUGUGGUACAUUACCUGGUA




UGGUUCU GCU UAAAGACU






















TABLE X











Homologous Hammerhead Ribozyme Target Sites






Between Human flt-1 and KDR RNA














nt.





nt.







Posi-




flt-1




Posi-




KDR






tion




Target Sequence




tion




Target Sequence









3388




CCGGGAU A UUUAUAA




3151




CCGGGAU A UUUAUAA













2174




AAUGUAU A CACAGGG




3069




AgUGUAU c CACAGGG













2990




UGCAAAU A UGGAAAU




2756




UGCAAAU u UGGAAAc













2693




CUCCCUU A UGAUGCC




2459




CUgCCUU A UGAUGCC













2981




GUUGAAU A CUGCAAA




2747




GUgGAAU u CUGCAAA













1359




UAUGGUU A AAAGAUG




2097




UgUGGUU u AAAGAUa













3390




GGGAUAU U UAUAAGA




3153




GGGAUAU U UAUAAAg













3391




GGAUAUU U AUAAGAA




3154




GGAUAUU U AUAAAgA













2925




ACGUGGU U AACCUGC




2691




AuGUGGU c AACCUuC













7140




UAUUUCU A GUCAUGA




2340




UACUUCU u GUCAUCA













1785




CAAUAAU A GAAGGAA




1515




CucUAAU u GAAGGAA













2731




GAGACUU A AACUGGG




 768




UUGACUU c AACUGGG













3974




GAUGACU A CCAGGGC




1466




GAgGACU u CCAGGGa













6590




UUAAUGU A GAAAGAA




2603




aaAAUGU u GAAAGAA













6705




GCCAUUU A UGACAAA




3227




aCaAUUU u UGACAgA













 974




GUCAAAU U ACUUAGA




 147




uUCAAAU U ACUUgCA













1872




AUAAAGU U GGGACUG




1602




ACAAAGU c GGGAgaG













2333




ACUUGGU U UAAAAAC




1088




AaaUGGU a UAAAAAU













2775




AAGUGGU U CAAGCAU




1745




AcaUGGU a CAAGCuU













3533




UUCUCCU U AGGUGGG




3296




UUuUCCU U AGGUGcu













3534




UCUCCUU A GGUGGGU




3297




UuUCCUU A GGUGcuU













3625




GUACUCU A CUCCUGA




4054




GagCUCU c CUCCUGu













1814




AGCACCU U GGUUGUG




1059




AGuACCU U GGUUacc













2744




GGCAAAU C ACUUGGA




 147




uuCAAAU u ACUUGcA













2783




CAAGCAU C AGCAUUU




 796




gAAGCAU C AGCAUaa













3613




GAGAGCU C CUGAGUA




2968




GgaAGCU C CUGAagA













4052




AAGGCCU C CCUCAAG




1923




ucuGCCU u GCUCAAG













5305




UCUCCAU A UCAAAAC




 456




ggUCCAU u UCAAAuC













7158




AUGUAUU U UGUAUAC




 631




gUcUAUU a UGUAcAu













1836




CUAGAAU U UCUGGAA




1007




aUgGAAU c UCUGGUg













2565




CUCUCUU C UGGCUCC




2328




uguUCUU C UGGCUaC













4250




CUGUACU C CACCCCA




3388




UUaUACU a CACCagA













7124




ACAUGGU U UGGUCCU




3778




cagUGGU a UGGUuCU













 436




AUGGUCU U UGCCUGA




1337




AcGGUCU a UGCCauu













2234




GCACCAU A CCUCCUG




1344




augCCAU u CCUCCcc













2763




GGGCUUU U GGAAAAG




 990




uuGCUUU U GGAAguG













4229




CCAGACU A CAACUCG




 767




auuGACU u CAACUgG













5301




GUUUUCU C CAUAUCA




3307




ugcUUCU C CAUAUCc













6015




AGAAUGU A UGCCUCU




1917




AcuAUGU c UGCCUug













6095




AUUCCCU A GUGAGCC




1438




AUaCCCU u GUGAaga













6236




UGUUGUU C CUCUUCU




 76




UagUGUU u CUCUUga













5962




GCUUCCU U UUAUCCA




3099




auaUCCU c UUAUCgg













7629




UAUAUAU U CUCUGCU




3096




gAAAUAU c CUCUuaU











Lowercase letters are used to represent sequence variance between flt-1 and KDR RNA





















TABLE XI











2.5 μmol RNA Synthesis Cycle



















Wait







Reagent




Equivalents




Amount




Time*





















Phosphoramidites




6.5




163




μL




2.5







S-Ethyl Tetrazole




23.8




238




μL




2.5







Acetic Anhydride




100




233




μL




 5 sec







N-Methyl Imidazole




186




233




μL




 5 sec







TCA




83.2




1.73




mL




21 sec







Iodine




8.0




1.18




mL




45 sec







Acetonitrile




NA




6.67




mL




NA













*Wait time does not include contact time during delivery.













Other embodiments are within the following claims.














SEQUENCE LISTING











The patent contains a lengthy “Sequence Listing” section. A copy of the “Sequence Listing” is available in electronic form from the USPTO






web site (http://seqdata.uspto.gov/sequence.html?DocID=06346398B1). An electronic copy of the “Sequence Listing” will also be available from the






USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).












Claims
  • 1. A nucleic acid molecule which specifically inhibits the synthesis, expression and/or stability of an mRNA encoding flt-1 receptor of human or mouse vascular endothelial growth factor, wherein said nucleic acid molecule is an enzymatic nucleic acid molecule or an antisense nucleic acid molecule.
  • 2. The nucleic acid of claim 1, wherein said nucleic acid molecule is an enzymatic nucleic acid molecule.
  • 3. The nucleic acid molecule of claim 2, wherein said enzymatic nucleic acid molecule comprises binding arms containing sequence complementary to a substrate nucleotide base sequence to any one of SEQ ID NOS; 1481-1482, 1493, 1574, 1664, 1669, 1838, 1847, 1913, 1933, 1974, 1984, 1997, 1999, 2000, 2025, 2130, 2382, or 2394.
  • 4. The nucleic acid molecule of claims 2, wherein said nucleic acid molecule is in a hammerhead motif.
  • 5. The nucleic acid molecule of claim 2, wherein said nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid or RNase P nucleic acid motif.
  • 6. A method of cleaving RNA of flt-1 gene comprising the step of contacting said RNA with the enzymatic nucleic acid molecule of claim 3, under conditions suitable for the cleavage of said RNA.
  • 7. The method claim 6, wherein said enzymatic nucleic acid molecule is in a hammerhead motif.
  • 8. The method of claim 6, wherein said enzymatic nucleic acid molecule comprises between 12 and 100 bases complementary to the RNA of flt-1 gene.
  • 9. The method of claim 6, wherein said enzymatic nucleic acid molecule comprises between 14 and 24 bases complementary to the RNA of flt-1 gene.
  • 10. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule comprises between 12 and 100 bases complementary to the RNA encoding the flt-1 receptor.
  • 11. The nucleic acid molecule of claim 10, wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to the RNA encoding the flt-1 receptor.
  • 12. A mammalian cell including a nucleic acid molecule of claim 1, wherein said mammalian cell is not a living human.
  • 13. The mammalian cell of claim 12, wherein said mammalian cell is a human cell.
  • 14. An expression vector comprising nucleic acid sequence encoding the nucleic acid molecule of claim 1, in a manner which allows expression and/or delivery of that nucleic acid molecule within a mammalian cell.
  • 15. The expression vector of claim 14, wherein said nucleic acid molecule is an enzymatic nucleic acid.
  • 16. A mammalian cell including an expression vector of claim 11, wherein said mammalian cell is not a living human.
  • 17. The mammalian cell of claim 16, wherein said mammalian cell is a human cell.
  • 18. The nucleic acid molecule of claim 1, wherein said nucleic acid molecule is an antisense nucleic acid molecule.
  • 19. The nucleic acid molecule of claim 18, wherein said antisense nucleic acid molecule contains sequence complementary to the substrate nucleotide base sequence selected from the group consisting of: 1481-1482, 1493, 1574, 1664, 1669, 1838, 1847, 1913, 1933, 1974, 1984, 1997, 1999, 2000, 2025, 2130, 2382, or 2394.
  • 20. An expression vector comprising nucleic acid sequence encoding the antisense nucleic acid molecule of claim 18, in a manner which allows expression and/or delivery of that antisense nucleic acid molecule within a mammalian cell.
  • 21. A mammalian cell including the expression vector of claim 20, wherein said mammalian cell is not a living human.
  • 22. The mammalian cell of claim 21, wherein said mammalian cell is a human cell.
  • 23. An enzymatic nucleic acid molecule comprising any ribozyme sequence selected from the group consisting of: SEQ ID NOS: 50-51, 62, 143, 233, 238, 407, 416-417, 482, 502, 543, 553, 566, 568-569, 574, 594, 699, 951, and 963.
RELATED APPLICATIONS

This application claims the benefit of Pavco et al., U.S. Ser. No. 60/005,974, entitled Method and Reagent for the Treatment of Diseases or Conditions Related to Levels of Vascular Endothelial Growth Factor Receptor, filed Oct. 26, 1995, which is incorporated by reference herein in its entirety, including drawings.

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Provisional Applications (1)
Number Date Country
60/005974 Oct 1995 US