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1. WO2004099372 - RIBOZYMES ANTI-CICATRISANTS ET METHODES ASSOCIEES

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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1. A ribozyme that specifically cleaves a target RNA sequence encoded by a CTGF gene.

2. The ribozyme of claim 1 , wherein the ribozyme is present in a hammerhead configuration.

3. The ribozyme of claim 2, wherein the ribozyme specifically cleaves target RNA sequences encoded by CTGF nucleotide sequences selected from the group consisting of SEQ ID NO's: 1-46.

4. An isolated nucleic acid encoding or comprising a hammerhead ribozyme according to claim 2, said nucleic acid having a sequence selected from the group consisting of SEQ ID NO's: 47 and 48 or a complement of SEQ ID NO's: 47 and 48.

5. An expression vector comprising an isolated nucleic acid encoding at least one ribozyme that specifically cleaves a target RNA sequence encoded by a CTGF nucleotide sequence selected from the group consisting of SEQ ID NO's: 1-46.

6. An expression vector comprising an isolated nucleic acid encoding a CTGF ribozyme selected from the group consisting of SEQ ID NO's: 47 and 48.

7. The expression vector of claim 6, wherein said vector is a plasmid.

8. The expression vector of claim 7, wherein the plasmid directs synthesis of a self-cleaving haiφin ribozyme attached to a CTGF ribozyme in a hammerhead configuration.

9. The expression vector of claim 8, wherein the plasmid is pTRUF21.

10. A method for reducing CTGF mRNA or protein expression in a cell, the method comprising the steps of: (a) providing a tissue comprising a cell expressing a target RNA sequence encoded by a CTGF gene; and
(b) contacting said tissue with a vector comprising a nucleic acid that encodes at least one ribozyme that specifically cleaves a target RNA sequence encoded by a CTGF gene, in an amount effective to reduce said CTGF mRNA or protein expression in said cell.

11. The method of claim 10, wherein said cell is a fibroblast.

12. The method of claim 10, further comprising contacting said tissue with said vector in a subject having or at risk for developing a condition causing a scar in said tissue.

13. The method of claim 12, wherein said condition is a fibrotic disorder.

14. The method of claim 13, wherein said fibrotic disorder is selected from the group consisting of scleroderma, keloids, liver cirrhosis, kidney fibrosis, peritoneal adhesions, tendon adhesions, breast implant capsule adhesions, burn scars, spinal cord injuries, bile duct atresia, subepithelial firbrosis, fibrous dysplasia, and tympanic membrane fibrosis.

15. The method of claim 13 , wherein said condition is wound healing following surgery.
16. The method of claim 15, wherein said surgery is corneal surgery.

17. The method of claim 15, wherein said surgery is glaucoma filtering surgery.

18. The method of claim 10, wherein said tissue is an ocular tissue selected from the group consisting of cornea, conjunctiva, sclera and trabecular meshwork.

19. A polyzyme that specifically cleaves a target RNA sequence encoded by a CTGF gene, said polyzyme comprising a plurality of conjoined ribozymes that specifically cleave at least one target RNA sequence encoded by a CTGF nucleotide sequence selected from the group consisting of SEQ ID NO's: 1-46.

20. The polyzyme of claim 19, wherein said ribozymes are separated by a G-C rich stem-loop structure.