Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype.
Despite the popularity of adeno-associated virus 2 (AAV2) as a vehicle for gene transfer, its efficacy for liver-directed gene therapy in hemophilia A or B has been suboptimal. Here we evaluated AAV serotypes 2, 5, 7, and 8 in gene therapy of factor VIII (FVIII) deficiency in a hemophilia A mouse model and found that AAV8 was superior to the other 3 serotypes. We expressed canine B domain-deleted FVIII cDNA either in a single vector or in 2 separate AAV vectors containing the heavy- and light-chain cDNAs. We also evaluated AAV8 against AAV2 in intraportal and tail vein injections. AAV8 gave 100% correction of plasma FVIII activity irrespective of the vector type or route of administration.
Sarkar
Rita
R
Department of Genetics, University of Pennsylvania 415 Curie Blvd, CRB Rm 475, Philadelphia, PA 19104, USA. sarkarr@mail.med.upenn.edu
Tetreault
Renee
R
Gao
Guangping
G
Wang
Lili
L
Bell
Peter
P
Chandler
Randy
R
Wilson
James M
JM
Kazazian
Haig H
HH
D000256:Adenoviridae / Q000145:classification / Q000235:genetics*; D000818:Animals; D015139:Blotting, Southern; D004274:DNA, Recombinant / Q000493:pharmacokinetics; D004285:Dogs; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006467:Hemophilia A / Q000235:genetics / Q000628:therapy*; D008099:Liver; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011169:Portal Vein; D013623:Tail / Q000098:blood supply
D004274:DNA, Recombinant; D005169:Factor VIII