Claims
- 1. An adenovirus/AAV hybrid virus comprising a recombinant adeno-associated viral (rAAV) vector, nucleic acid sequences encoding adenovirus E1 a and adenovirus E1b are under the control of regulatory sequences directing expression of the E1a and E1b gene products, wherein said hybrid virus contains sufficient adenoviral sequences to permit replication of said hybrid virus in a selected host cell.
- 2. The adenovirus/AAV hybrid virus according to claim 1 further comprising a functional deletion in the E3 region.
- 3. The adenovirus/AAV hybrid virus according to claim 1 further comprising a non-functional deletion of adenoviral coding sequences in the E4 region, wherein said hybrid virus contains the E4 ORF6 region.
- 4. The adenovirus/AAV hybrid virus according to claim 1, wherein said E1a and E1b nucleic acid sequences are located in the site of the wild-type E3 region.
- 5. The adenovirus/AAV hybrid virus according to claim 4, wherein said rAAV vector is located in the wild-type adenoviral E1a and E1b region.
- 6. The adenovirus/AAV hybrid virus according to claim 1, wherein the AAV vector comprises AAV 5′ and 3′ inverted terminal repeats (ITRs) and a transgene under the control of regulatory sequences directing expression thereof.
- 7. The adenovirus/AAV hybrid virus according to claim 1, wherein the regulatory sequences comprise a first promoter which directs the expression of the E1a gene product.
- 8. The adenovirus/AAV hybrid virus according to claim 7, wherein the first promoter is selected from the group consisting of a native promoter of E1a, an inducible promoter, a tissue-specific promoter, and a constitutive promoter.
- 9. The adenovirus/AAV hybrid virus according to claim 1, wherein the regulatory sequences comprise a second promoter which directs the expression of the adenoviral E1b gene product.
- 10. The adenovirus/AAV hybrid virus according to claim 9, wherein the second promoter is identical to the first promoter.
- 11. The adenovirus/AAV hybrid virus according to claim 9, wherein the second promoter and the first promoter are different.
- 12. The adenovirus/AAV according to claim 1, wherein said virus further comprises a temperature sensitive mutation in the adenoviral E2b gene.
- 13. An adenovirus/AAV hybrid virus comprising:
(a) adenovirus 5′ cis-elements necessary for replication and packaging; (b) a deletion of adenoviral sequences in the native adenoviral E1a and E1b region; (c) a recombinant adeno-associated viral (rAAV) vector; (d) a deletion of adenoviral sequences from the E3 region; (e) nucleic acid sequences encoding adenovirus E1 a and adenovirus E1b under the control of regulatory sequences directing expression of the E1a and E1b gene products, wherein said E1a and E1b nucleic acid sequences are located in the site of the E3 region and; (f) adenovirus 3′ cis-elements necessary for replication and packaging.
- 14. The hybrid adenovirus/AAV virus according to claim 13, wherein said hybrid adenovirus/AAV virus further comprises nucleic acid sequences encoding adenoviral E2a gene product under the control of regulatory sequences which direct expression thereof in a host cell.
- 15. The hybrid adenovirus/AAV virus according to claim 13, wherein said hybrid adenovirus/AAV virus further comprises nucleic acid sequences encoding adenoviral E4 gene product or a functional fragment thereof under the control of regulatory sequences which direct expression thereof in a host cell.
- 16. The hybrid adenovirus/AAV virus according to claim 15, wherein said functional fragment of E4 gene product is E4 ORF6.
- 17. The hybrid adenovirus/AAV virus according to claim 13, further comprising adenoviral sequences encoding VAI RNA.
- 18. A mammalian host cell containing an adenovirus/AAV hybrid virus according to claim 1.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a divisional of U. S. patent application Ser. No. 09/404,555, filed Sep. 23, 1999 which is a continuation-in-part of International Patent Application PCT/US99/05870, filed Mar. 18, 1999.
Divisions (1)
|
Number |
Date |
Country |
Parent |
09404555 |
Sep 1999 |
US |
Child |
09826510 |
Apr 2001 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
PCT/US99/05870 |
Mar 1999 |
US |
Child |
09404555 |
Sep 1999 |
US |