Claims
- 1. An adenovirus vector comprising
(a) an adenovirus gene under transcriptional control of a target cell-specific transcriptional regulatory element (TRE); and (b) an E3 sequence.
- 2. The adenovirus vector of claim 1, wherein the adenovirus gene is essential for replication.
- 3. The adenovirus vector of claim 2, wherein the adenovirus gene is an early gene.
- 4. The adenovirus vector of claim 3, wherein the early gene is E1A.
- 5. The adenovirus vector of claim 3, wherein the early gene is E1B.
- 6. The adenovirus vector of claim 3, wherein the early gene is E2.
- 7. The adenovirus vector of claim 3, wherein the early gene is E4.
- 8. The adenovirus vector of claim 1, wherein the target cell-specific TRE is cell type specific.
- 9. The adenovirus vector of claim 8, wherein the cell type-specific TRE is prostate cell specific.
- 10. The adenovirus vector of claim 9, wherein the TRE is a PSA-TRE.
- 11. The adenovirus vector of claim 9, wherein the TRE is a PB-TRE.
- 12. The adenovirus vector of claim 8, wherein the cell type-specific TRE is liver cell specific.
- 13. The adenovirus vector of claim 12, wherein the TRE is an AFP-TRE.
- 14. The adenovirus vector of claim 8, wherein the cell type-specific TRE is breast cancer cell-specific.
- 15. The adenovirus vector of claim 14, wherein the TRE is a MUC 1-TRE.
- 16. The adenovirus vector of claim 14, wherein the TRE is a CEA-TRE.
- 17. The adenovirus vector of claim 16, wherein the CEA-TRE comprises nucleotides −6072 to −3815 to −300 to +70 relative to the CEA gene transcription start site.
- 18. The adenovirus vector of claim 8, wherein the cell type-specific TRE is colon cancer cell-specific.
- 19. The adenvoirus vector of claim 8, wherein the TRE is an hKLK2-TRE.
- 20. The adenovirus vector of claim 1, wherein the target cell-specific TRE is cell status specific.
- 21. The adenovirus vector of claim 20, wherein the cell status-specific TRE comprises a hypoxia-responsive element.
- 22. The adenovirus of claim 1 comprising an adenoviral gene under transcriptional control of a cell status-specific TRE and a cell type-specific TRE.
- 23. The adenovirus of claim 22, wherein the cell status-specific TRE comprises a hypoxia-responsive element (HRE) and the cell type-specific TRE is a prostate-specific antigen TRE (PSA-TRE).
- 24. The adenovirus vector of claim 23, wherein the HRE comprises the nucleotide sequence depicted in SEQ ID NO:9.
- 25. The adenovirus vector of claim 24, wherein the PSA-TRE comprises nucleotides −5322 to −3738 and −541 to +12 relative to the PSA gene transcription start site.
- 26. The adenovirus vector of claim 1, wherein the E3 sequence is under transcriptional control of a target cell-specific TRE.
- 27. An adenovirus vector comprising (a) an E3 sequence; and (b) a first adenovirus gene under transcriptional control of a first target cell-specific transcriptional response element (TRE) and a second gene under transcriptional control of a second target cell-specific TRE.
- 28. The adenovirus vector of claim 27, wherein the first adenovirus gene is essential for adenovirus replication.
- 29. The adenovirus vector of claim 27, wherein the gene essential for replication is an adenovirus early gene.
- 30. The adenovirus vector of claim 29, wherein the early gene is E1A.
- 31. The adenovirus vector of claim 29, wherein the early is E1B.
- 32. The adenovirus vector of claim 29, wherein the early gene is E2.
- 33. The adenovirus vector of claim 29, wherein the early gene is E4.
- 34. The adenovirus vector of claim 27, wherein the first and second genes are essential for adenovirus replication.
- 35. The adenovirus vector of claim 34, wherein the first and second genes are adenovirus early genes.
- 36. The adenovirus vector of claim 27, wherein the second gene is a transgene.
- 37. The adenovirus vector of claim 36, wherein said transgene is a cytotoxic gene.
- 38. The adenovirus vector of claim 27, wherein the first and second target cell-specific TREs are cell-type specific and functional in the same cell.
- 39. The adenovirus vector of claim 29, wherein the first and second target cell-specific TREs are prostate cell-specific.
- 40. The adenovirus vector of claim 39, wherein the first TRE is a PB-TRE.
- 41. The adenovirus vector of claim 39, wherein the second TRE is a PSA-TRE.
- 42. The adenovirus vector of claim 39, wherein the first TRE is a PB-TRE and the second TRE is a PSA-TRE.
- 43. The adenovirus vector of claim 42, wherein the PB-TRE comprises nucleotides −426 to +28 relative to the rat probasin gene transcription start site, and the PSA-TRE comprises nucleotides −5322 to −3738 and −541 to +12 relative to the PSA gene transcription start site.
- 44. The adenovirus vector of claim 27, wherein the first and second target cell-specific TREs are liver cell-specific.
- 45. The adenovirus vector of claim 44, wherein the first and second TREs are AFP-TREs.
- 46. The adenovirus vector of claim 45, wherein the AFP-TREs comprise nucleotides −3954 to −3335 and −174 to +29 relative to the AFP gene transcription start site.
- 47. The adenovirus vector of claim 46, wherein the first and second TREs are colon cancer cell-specific.
- 48. The adenovirus vector of claim 47, wherein the first and second TREs are CEA-TREs.
- 49. An isolated host cell comprising the adenovirus vector of claim 1.
- 50. An isolated host cell comprising the adenovirus vector of claim 27.
- 51. A composition comprising the adenovirus vector of claim 1.
- 52. A composition comprising the adenovirus vector of claim 27.
- 53. A method for conferring selective cytotoxicity on a cell which allows a target cell-specific TRE to function, comprising contacting said cell with an adenovirus vector of claim 2, wherein the adenovirus vector enters the cell.
- 54. A method according to claim 53, wherein cell is a mammalian cell.
- 55. A method according to claim 54, wherein the mammalian cell is a prostate cell.
- 56. A method according to claim 54, wherein the mammalian cell is a liver cell.
- 57. A method according to claim 54, wherein the mammalian cell is a breast cancer cell.
- 58. A method according to claim 55, wherein the mammalian cell is a colon cancer cell.
- 59. A method for propagating an adenovirus vector of claim 1, said method comprising combining an adenovirus vector of claim 1 with cells which allow function of the target cell-specific TRE, whereby said adenovirus is propagated.
- 60. A method according to claim 59, wherein the cells are mammalian cells.
- 61. A method for suppressing tumor growth comprising contacting a tumor cell with an adenovirus vector according to claim 2 such that the adenovirus vector is introduced into the tumor cell.
- 62. A method according to claim 61, wherein the tumor cell is a mammalian cell.
- 63. A method according to claim 62, wherein the mammalian cell is a prostate cell.
- 64. A method according to claim 61, wherein the mammalian cell is a liver cell.
- 65. A method according to claim 61, wherein the mammalian cell is a breast cancer cell.
- 66. A method according to claim 61, wherein the mammalian cell is a colon cancer cell.
- 67. A method for modifying the genotype of a target cell comprising contacting the target cell with the adenovirus vector according claim 1 such that the adenovirus vector is introduced into the target cell.
- 68. A replication competent adenovirus vector comprising an E3 sequence under transcriptional control of a target cell-specific TRE.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the priority benefit of U.S. Provisional Patent Application No. 60/114,262, filed Dec. 30, 1998. The priority application is hereby incorporated herein by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60114262 |
Dec 1998 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09474699 |
Dec 1999 |
US |
Child |
10226820 |
Aug 2002 |
US |