Non-group C adenoviral vectors

• US 5,837,511 A
• Filed: 10/02/1995
• Issued: 11/17/1998
• Est. Priority Date: 10/02/1995
• Status: Expired due to Term

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Mastrangeli, Andrea, Abrahamson, Karil, Crystal, Ronald G., Falck-Pedersen, Erik S.
• Primary Examiner(s): Chambers, Jasemine C.
• Assistant Examiner(s): REYNOLDS, DEBORAH J
• Application Number:
  US08/537,402
• Time in Patent Office: 1,142 Days
• Field of Search: 435/320.1, 435/5, 435/6, 435/4, 435/235.1, 514/44, 424/93.1, 424/93.2, 424/9
• US Class Current: 435/6.12
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector

Abstract

The present invention provides replication-deficient non-group C adenoviral vectors. Also provided is a therapeutic method, particularly relating to gene therapy, vaccination, and the like, involving the use of such vectors incorporating a foreign nucleic acid.

Claims

1. A stock of a replication deficient adenoviral gene transfer vector, said vector comprising (a) an expression cassette that encodes a foreign gene product, and (b) an adenoviral DNA segment isolated from an adenovirus selected from the group consisting of A, B, D, E and F adenovirus, wherein said vector stock is free of replication competent adenovirus.

2. The vector stock of claim 1, wherein said vector is deficient in at least the E1A region of the adenoviral genome.

3. The vector stock of claim 2, wherein said adenovirus is a group B adenovirus.

4. The vector stock of claim 3, wherein said adenovirus is an Ad7adenovirus.

5. The vector stock of claim 2, wherein said vector replicates in the HEK-293 cell line.

6. The vector stock of claim 2, wherein said vector is further deficient in at least another region of the adenoviral genome.

7. The vector stock of claim 2, wherein said vector is further deficient in at least another region of the adenoviral genome required for viral replication.

8. The vector stock of claim 2, wherein said vector is further deficient in a region selected from the group consisting of the E1B, E2, E3, and E4 regions of the adenoviral genome.

9. The vector stock of claim 2, wherein said vector is further deficient in a region selected from the group consisting of the late regions of the adenoviral genome.

10. A method of testing the expression of a foreign gene product upon transfection into an isolated target cell, which method comprises (a) selecting a target cell, (b) contacting said target cell with the vector stock of claim 1, and (c) determining the expression of said foreign gene product in said isolated target cell.

11. The vector stock of claim 2, wherein said stock is propagated in a cell line that complements in trans a group C adenovirus deficient in the E1A region of the adenoviral genome.

12. The vector stock of claim 11, wherein said cell line is an HEK-293 cell line.

13. A method of growing and propagating an isolated non-group C adenoviral vector stock in the absence of a helper virus which method comprises

contacting a cell of a cell line that is capable of complementing the replication of a group C adenovirus that is deficient in at least the E1A region of the adenoviral genome

with a non-group C adenovirus deficient in at least the E1A region of the adenoviral genome.

14. The method of claim 13, wherein said cell line is an HEK-293 cell line.

15. The method of claim 13, wherein said vector is further deficient in another region of the adenoviral genome.

16. The method of claim 13, wherein said non-group C vector is of group B.

17. The method of claim 16, wherein said group B vector is an Ad7 adenovirus.