Novel therapeutic approach for hemophilia using gene delivery of an engineered secreted activated Factor VII.

摘要: Hemophilia is a bleeding disorder caused by mutations in the genes encoding coagulation Factor VIII (FVIII) or FIX. Current treatment through intravenous infusion of missing protein. The major complication development neutralizing Ab's to clotting factor. Infusion recombinant activated human VII (rhFVIIa), driving procoagulant reactions independently FVIII (hFVIII) hFIX, has been successful such patients and could theory provide hemostasis all hemophilia patients. However, its high cost short half-life have limited use. Here, we report novel strategy with adeno-associated virus vector delivering modified FVII transgene that can be intracellularly processed secreted as (FVIIa). We show long-term expression, well phenotypic correction B mice following gene transfer murine FVIIa homolog, no evidence thrombotic complications at these doses. These data hold promise for potential other disorders.