Claims
- 1. A method for transducing marrow stromal cells, said method comprising infecting marrow stromal cells with a vector which comprises a bicistronic coding region comprising a nucleic acid encoding tyrosine hydroxylase type I (TH) and a sequence encoding GTP cyclohydrolase I (GC), operably linked to a promoter/regulatory region, thereby transducing the marrow stromal cell.
- 2. The method of claim 1, wherein said vector is selected from the group comprising a virus and a plasmid.
- 3. The method of claim 2, wherein said virus is a retrovirus.
- 4. The method of claim 3, wherein said retrovirus is a self-inactivating retrovirus.
- 5. The method of claim 1, wherein said nucleic acid encoding TH and said nucleic acid encoding GC are separated by an internal ribosomal entry site (IRES).
- 6. The transduced marrow stromal cell of claim 1, wherein said marrow stromal cell is a human marrow stromal cell.
- 7. The transduced marrow stromal cell of claim 1, wherein said marrow stromal cell is a rat marrow stromal cell.
- 8. A method of treating Parkinson's disease, said method comprising administering to a patient marrow stromal cells transduced by the method of claim 1, wherein said administration of said marrow stromal cells alleviates symptoms of Parkinson's disease.
- 9. A method of treating a disease characterized by a deficiency in 3,4-dihydroxyphenylalanine (L-DOPA), said method comprising administering to a patient a marrow stromal cell transduced by the method of claim 1, wherein said administration of said marrow stromal cells regulates the production of L-DOPA causing alleviation of symptoms of said disease.
- 10. A method for producing exogenous L-DOPA, said method comprising transducing a marrow stromal cell by the method of claim 1 and expressing tyrosine hydroxylase type I (TH) and GTP cyclohydrolase I (GC) in said marrow stromal cell thereby producing exogenous L-DOPA.
- 11. A vector construct comprising a nucleic acid encoding TH and GC separated by an internal ribosomal entry site (IRES).
- 12. The vector construct of claim 11, wherein a promoter sequence is operably linked to the nucleic acids encoding TH and GC.
- 13. The vector construct of claim 12, wherein said promoter sequence is selected from the group consisting of cytomegalovirus promoter, phosphoglycerate kinase-1 promoter, or human histone H4.
- 14. The vector construct of claim 12, wherein said promoter sequence is cytomegalovirus promoter.
- 15. The vector construct of claim 12, wherein said promoter sequence is phosphoglycerate kinase promoter.
- 16. The vector construct of claim 13, wherein said vector is retroviral.
- 17. The vector construct of claim 16, wherein said vector is a self-inactivating retrovirus.
- 18. The vector construct of claim 11, wherein the vector is selected from the group consisting of murine leukemia viral vector (LXSN), murine stem cell viral vector (MSCV) and a self-inactivating retroviral vector, wherein said self-inactivating retroviral vector further comprises a promoter selected from the group consisting of cytomegalovirus and phosphoglycerate kinase promoter.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 60/298,150, filed Jun. 14, 2001.
STATEMENT REGARDING FEDERALLY SUPPORTED RESEARCH AND DEVELOPMENT
[0002] The invention was made in part using funds obtained from the U.S. Government (National Institutes of Health Grant Nos. AR47161 and A42210) and the U.S. government may have certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60298150 |
Jun 2001 |
US |