Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype.

Abstract

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.

• Authors: Rita Sarkar, Renee Tetreault, Guangping Gao, Lili Wang, Peter Bell, Randy Chandler, James M Wilson, Haig H Kazazian Jr
• Journal: Blood (Blood) Vol. 103 Issue 4 Pg. 1253-60 (Feb 15 2004) ISSN: 0006-4971 [Print] United States
• PMID: 14551134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Recombinant
• Factor VIII

Topics

• Adenoviridae (classification, genetics)
• Animals
• Blotting, Southern
• DNA, Recombinant (pharmacokinetics)
• Dogs
• Factor VIII (genetics)
• Female
• Genetic Therapy (methods)
• Genetic Vectors
• Hemophilia A (genetics, therapy)
• Liver
• Male
• Mice
• Mice, Mutant Strains
• Portal Vein
• Tail (blood supply)