文献类型：期刊文献

英文题名：Activated factor X delivered by adeno-associated virus significantly inhibited bleeding and alleviated hemophilic synovitis in hemophilic mice

作者：Zhang, Feixu[1];Zhou, Xinyue[2];Hua, Baolai[3];He, Xinyi[2];Li, Zhanao[2];Xiao, Xiao[1,2];Wu, Xia[2]

机构：[1]East China Univ Sci & Technol, Sch Biotechnol, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai, Peoples R China;[3]Capital Med Univ, Beijing Shijitan Hosp, Dept Hematol, Beijing, Peoples R China

年份：2024

卷号：31

期号：11-12

起止页码：544

外文期刊名：GENE THERAPY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001309206200001)】；

基金：We appreciate the AAV gene therapy and virus packaging services from Belief BioMed, Inc.

语种：英文

摘要：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.