Aav vector for gene therapy

• US 20070036757A1
• Filed: 06/09/2004
• Published: 02/15/2007
• Est. Priority Date: 06/11/2003
• Status: Active Grant

• Current Assignee: Jurgen Kleinschmidt, Oliver Muller
• Original Assignee: Jurgen Kleinschmidt, Oliver Muller
• Inventors: Muller, Oliver, Kleinschmidt, Jurgen
• Granted Patent: US 7,629,322 B2
• Time in Patent Office: Days
• US Class Current: 424/93.200
• 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: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2750/14145 Special targeting system for viral vectors
• CPC Class Codes: C12N 2810/60 from viruses

Abstract

Described are recombinant AAV vectors characterized in that they carry capsid protein modification(s) resulting in a reduced or eliminated heparin binding function. The AAV vectors of the present invention are particularly suitable for gene therapy by systemic application, since (a) transduction of the liver is eliminated or at least drastically reduced and (b) the transduction efficiency of non-hepatic tissues is increased.

Claims

1. An AAV vector characterized in that it carries at least one mutation resulting in a heparin-binding motif of a capsid protein being located within aa positions 470 to 592 showing a reduced or eliminated heparin binding function.

2. The AAV vector of claim 1, wherein said mutation results in an amino acid substitution of the capsid protein at aa position:

(a) arginine 475;

(b) arginine 484;

(c) arginine 487;

(d) lysine 527;

(e) lysine 532;

(f) arginine 585; and

/or

(g) arginine 588.

3. The AAV vector of claim 2, wherein said amino acid substitution is a non-conservative amino acid substitution

4. The AAV vector of claim 3 with the capsid protein being characterized by at least one of the following amino acid substitutions.

(a) R475A;

(b) R484A or R484E;

(c) R487A or R487E;

(d) K527A;

(e) K532A;

(f) R585E; and

/or

(g) R588E.

5. The AAV vector of claim 4 with the capsid protein being characterized by the amino acid substitutions R484E and/or 585E.

6. The AAV vector of claim 1, which is an AAV-2 vector.

7. An AAV particle having a capsid encoded by an AAV vector of claim 1.

8. A pharmaceutical composition containing an AAV vector of claim 1.

9. Use of an AAV vector of claim 1 for gene therapy of non-hepatic tissue.

10. The use according to claim 9, wherein said non-hepatic tissue is heart muscle tissue.