IP Library › Granted Patent US 9,732,359
Granted Patent B2
US 9,732,359 · App. 14/963,172 · Granted Aug 15, 2017

Replication-competent adenoviral vectors

Inventors: Bo Peng (Rockville, MD); Rebecca Voltan (Ferrara, IT); Barbara Ensoli (Rome, IT); Marjorie Robert-Guroff (Rockville, MD)
Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services; Istituto Superiore di Sanita
C12N15/86A61K39/21C07K14/005C12N7/00A61K2039/5256A61K2039/575C12N2710/10043C12N2710/10343C12N2710/16143C12N2740/15034C12N2740/15071C12N2740/16034C12N2740/16071C12N2740/16134C12N2740/16234C12N2740/16334
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Quick Facts
Patent No.
US 9,732,359
App. No.
14/963,172
Granted
Aug 15, 2017
Kind
B2
Abstract

This invention provides improved replication-competent adenoviral vectors. The improved vectors have both a hybrid regulatory unit that provides for high level transgene expression. The vectors can be use, e.g., for therapeutic or prophylactic purposes.

Claims (21)

1. A method of enhancing expression of a transgene in a host cell, the method comprising introducing a replication adenovirus vector into a host cell, wherein the adenovirus vector comprises an endogenous adenovirus tripartite leader sequence and a hybrid expression cassette comprising a cytomegalovirus (CMV) immediate early promoter, a second adenovirus tripartite leader sequence, and the transgene; and expressing the transgene in the host cell.

2. The method of claim 1 , wherein the adenovirus vector is selected from the group consisting of adenovirus type 2, adenovirus type 4, adenovirus type 5, and adenovirus type 7.

3. The method of claim 2 , wherein the adenovirus vector is adenovirus type 2.

4. The method of claim 2 , wherein the adenovirus vector is adenovirus type 4.

5. The method of claim 2 , wherein the adenovirus vector is adenovirus type 5.

6. The method of claim 2 , wherein the adenovirus vector is adenovirus type 7.

7. The method of claim 1 , wherein the adenovirus vector lacks a functional E3 region.

8. The method of claim 7 , wherein the vector is deleted in the E3 region.

9. The method of claim 7 , wherein the transgene is an HIV gene.

10. The method of claim 9 , wherein the HIV gene is an HIV regulatory gene.

11. The method of claim 10 , wherein the HIV regulatory gene encodes Nef or Tat.

12. The method of claim 11 , wherein the HIV regulatory gene encodes Nef.

13. The method of claim 12 , wherein Nef is not myristoylated.

14. The method of claim 11 , wherein the HIV regulatory gene encodes Tat.

15. The method of claim 14 , wherein the Tat lacks transactivation function.

16. The method of claim 9 , wherein the HIV gene is an HIV structural gene.

17. The method of claim 15 , wherein the HIV structural gene encodes Gag or Env.

18. The method of claim 8 , wherein the hybrid expression cassette is inserted into the deleted E3 region.

19. The method of claim 1 , wherein the second adenovirus tripartite leader sequence is a spliced tripartite leader sequence.

20. The method of claim 1 , wherein the second adenovirus tripartite leader sequence comprises the sequence of SEQ ID NO: 1.

21. The method claim 1 , wherein the second adenovirus tripartite leader sequence comprises the sequence of SEQ ID NO: 2.

Continuity (4)
Division 14571942 · Dec 16, 2014
Division 11282319 · Nov 17, 2005
Provisional Application 60629722 · Nov 18, 2004
Related Publication 20160090606A1 · Mar 31, 2016