Adeno-associated viral vector gene therapy for canine hemophilia

Abstract

Hemophilia A (HA) and B (HB) are monogenic X-linked disorders caused by plasma coagulant factor VIII (FVIII) and IX (FIX) deficiency, respectively, and occur naturally in a variety of dog breeds. While several animal models of hemophilia exist, the canine model closely mimics the genotypic, phenotypic, and immunologic characteristics of the disorder in humans. Consequently, decades of research were conducted in the canine model of hemophilia, ultimately leading to licensed liver-directed adeno-associated viral (AAV) vector-mediated gene therapy for HA and HB in humans. The studies from both research colony and companion hemophilic dogs with AAV liver-directed gene therapy support the safety and efficacy of this platform in canines. Here, we provide practical considerations with respect to the administration and monitoring of liver-directed AAV gene therapy for hemophilia in veterinary clinical practice and review the data on efficacy and safety of AAV gene therapy in canine hemophilia.

Keywords

Hemophilia / AAV / gene therapy / dogs

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