Claims
- 1. A method for expressing human FGF-5 in human cells without inducing tumorigenicity, comprising:
a) introducing a nucleic acid sequence encoding human FGF-5 without a signal sequence (hereinafter “FGF-5 fragment”) into a replication defective viral vector that infects human cells, said viral vector being an adenoviral vector or an AAV vector, said FGF-5 having angiogenic activity but not tumorigenic activity, said nucleic acid sequence being operably linked to a promoter for expression in said human cells; and b) infecting said human cells with said vector containing said sequence to cause said human cells to express an angiogenic inducing amount of said FGF-5 without causing said human cells to become tumorigenic.
- 2. The method of claim 1, wherein the nucleic acid sequence has the sequence TTCTTCAGCC ACCTGATCCT CAGC (SEQ ID NO:2) encoding the N terminus of said FGF-5 fragment.
- 3. The method of claim 1, wherein the nucleic acid sequence has the sequence ATCCTCAGCG CCTGGGCTCA CGGG (SEQ ID NO:3) encoding the N terminus of said FGF-5 fragment.
- 4. The method of claim 1, wherein the nucleic acid sequence has the sequence GGGAGAAGCG TCTCGCCCCC AAAG (SEQ ID NO:1) encoding the N terminus of said FGF-5 fragment.
- 5. The method of claim 1, wherein the nucleic acid sequence has the sequence CGTCTCGCCC CCAAAGGGCA ACCC (SEQ ID NO:4) encoding the N terminus of said FGF-5 fragment.
- 6. The method of claim 1, wherein the nucleic acid sequence has the sequence GGGCAACCCG GACCCGCTGC CACT (SEQ ID NO:5) encoding the N terminus of said FGF-5 fragment.
- 7. The method of claim 1, wherein said FGF-5 fragment comprises the FGF-5 of SEQ ID NO:7 lacking the first 59 of the first 61 residues from its N terminus.
- 8. The method of claim 1, wherein the replication defective viral vector is an adenoviral vector.
- 9. The method of claim 1, wherein the replication defective viral vector is administered into the intrapericardial space of a human patient in need of angiogenesis.
- 10. The method of claim 9, wherein the replication defective viral vector is used to treat myocardial ischemia or peripheral vascular disease.
- 11. A method for introducing a non-tumorigenic FGF-5 gene into a human cell in an area of the human myocardium afflicted by myocardial ischemia comprising:
a) constructing a viral vector that infects human cells, said viral vector being an adenoviral vector or an AAV vector having a nucleic acid sequence encoding human FGF-5 without a signal sequence (hereinafter “FGF-5 fragment”) in operable linkage with the appropriate regulatory elements necessary to express the nucleic acid sequence in a human cell, said nucleic acid sequence having the sequence GGGAGAAGCG TCTCGCCCCC AAAG (SEQ ID NO:1) encoding the N terminus of the FGF-5 fragment; and b) injecting said viral vector in an area of said myocardium afflicted by myocardial ischemia to infect said cells in said area with said vector, said FGF-5 fragment being expressed in said cells in an angiogenic inducing amount without inducing said cells to become tumorigenic.
- 12. The method of claim 11, wherein said FGF-5 fragment comprises the FGF-5 of SEQ ID NO:7 lacking the first 59 of the first 61 residues from its N terminus.
- 13. A method for introducing a non-tumorigenic human FGF-5 gene into a human heart cell in vivo comprising:
a) constructing a viral vector that infects human cells, said viral vector being an adenoviral vector or an AAV vector having a nucleic acid sequence encoding human FGF-5 without a signal sequence (hereinafter “FGF-5 fragment”) in operable linkage with the appropriate regulatory elements necessary to express the nucleic acid sequence in a human cell; and b) injecting said viral vector into the pericardial space of a human patient, said vector infecting human heart cells enclosed within said pericardial space and expressing said FGF-5 fragment therein, said FGF-5 fragment being free of tumorigenic activity.
- 14. The method of claim 13, wherein said FGF-5 fragment comprises the FGF-5 of SEQ ID NO:7 lacking the first 59 of the first 61 residues from its N terminus.
- 15. A pharmaceutical composition comprising:
a) an angiogenically inducing effective amount of a viral expression vector that infects a human cell, said viral expression vector being an adenoviral vector or an AAV vector and comprising a nucleic acid sequence encoding human FGF-5 without a signal sequence (hereinafter “FGF-5 fragment”), said nucleic acid sequence being operably linked to a promoter for expression in said human cell, said FGF-5 fragment having angiogenic activity but not tumorigenic activity; and b) a pharmaceutically acceptable carrier.
- 16. The pharmaceutical composition of claim 15, wherein said viral vector is an adenoviral vector.
- 17. The pharmaceutical composition of claim 15, wherein said viral vector is replication defective.
- 18. A pharmaceutical composition comprising:
a) a viral expression vector that infects a human cell, said viral expression vector being an adenoviral vector or an AAV vector and comprising a nucleic acid sequence encoding human FGF-5 without a signal sequence (hereinafter “FGF-5-Fragment”), said nucleic acid sequence being operably linked to a promoter for expression in said human cell, said FGF-5 fragment having angiogenic activity but not tumorigenic activity; and b) a pharmaceutically acceptable carrier.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of U.S. patent application Ser. No. 08/602,147, filed Feb. 15, 1996, the content of which is herein incorporated by reference in its entirety.
Continuations (1)
|
Number |
Date |
Country |
Parent |
08602147 |
Feb 1996 |
US |
Child |
10023592 |
Dec 2001 |
US |