Activated factor X delivered by adeno-associated virus significantly inhibited bleeding and alleviated hemophilic synovitis in hemophilic mice.

In hemophilia, deficiency of factor VIII or IX prevents the activation of the common coagulation pathway, and inhibits the conversion of FX to activated FXa, which is required for thrombin generation. We hypothesized that the direct expressed FXa has the potential to activate the common pathway and restore coagulation in hemophilia patients. In this study, the cassettes that expressed FXa, FXaop and FXa-FVII were packaged into an engineered AAV capsid, AAV843, and were delivered into hemophilia A and B mice by intravenous injection. AAV-FXaop could be stably expressed in vivo and showed the best immediate and prolonged hemostatic effects, similar to those of commercial drugs (Xyntha and Benefix). AAV-FXaop also significantly inhibited bleeding in hemophilia A mice with inhibitors. In addition, FXa expression in joints significantly alleviated the occurrence of hemophilic synovitis. AAV-delivered FXa may be a novel target for treating hemophilic and hemophilic synovitis.

Zhang F ，Zhou X ，Hua B ，He X ，Li Z ，Xiao X ，Wu X ... -  《-》

Intraarticular factor IX protein or gene replacement protects against development of hemophilic synovitis in the absence of circulating factor IX.

Sun J ，Hakobyan N ，Valentino LA ，Feldman BL ，Samulski RJ ，Monahan PE ... -  《-》

Exploring the Potential Feasibility of Intra-Articular Adeno-Associated Virus-Mediated Gene Therapy for Hemophilia Arthropathy.

Zhang F ，Yan X ，Li M ，Hua B ，Xiao X ，Monahan PE ，Sun J ... -  《-》

Zymogen-like factor Xa variants restore thrombin generation and effectively bypass the intrinsic pathway in vitro.

Bunce MW ，Toso R ，Camire RM 《-》

Adeno-associated virus-mediated gene transfer for hemophilia B.

High KA 《INTERNATIONAL JOURNAL OF HEMATOLOGY》