血友病A的定点基因治疗研究进展

Progress in Targeted Gene Therapy for Hemophilia A

约80%~85%的血友病患者为血友病A(hemophilia A,HA),目前还没有根治疗法。临床上通过定期输注血浆来源的或者重组的凝血因子Ⅷ浓缩蛋白行替代治疗。如果不进行定期治疗,HA患者常可因关节内反复出血而导致关节炎。重度患者甚至可因颅内自发出血而危及生命。自从F8在四十年前被成功克隆以来,HA的基因治疗研究最常使用的方案是随机导入一个功能性的F8表达框。随着近些年基因编辑技术的快速发展,定点基因治疗正逐渐成为一个重要的研究策略。

Hemophilia A(HA),without a radical cu re,constitutes 80%-85%of all hemophiliac cases.Current treatments are based on intravenous infusion of plasma-derived or recombinant FⅧconcentrates.HA patients suffer from recurrent bleeding into joints without conventional treatment,ca using chronic synovitis.In severe patients(FⅧ<1%),hemorrhage into the brain can develop,ca using ea rly mortality.Since the cloning of F8 nearly 40 years ago,introduction of a functional F8 cassette has become the main strategy for HA gene therapy studies.With the rapid development of editing,targeted gene therapy for HA offers an alternative over gene replacement st rategies.