靶向血小板表达FⅧ基因治疗血友病A的新进展

Research advances on platelet-targeted gene therapy for hemophilia A

基因治疗是一种颇具临床应用前景的血友病A(HA)治疗方法,人体内有多种细胞可作为基因治疗HA的靶细胞。为克服靶向肝细胞基因治疗HA的缺陷,研究者们开发了靶向血小板表达FⅧ的基因治疗策略。该策略应用不同的血小板特异性启动子,从而实现靶向血小板的FⅧ表达,常用启动子包括血小板糖蛋白αⅡb启动子,血小板糖蛋白Ⅰb启动子,血小板因子4启动子等。该策略主要具有如下优势。首先,大量FⅧ在需要止血的损伤局部聚集,促进止血并激活凝血反应。其次,FⅧ储藏在血小板的α颗粒内,极大地降低了FⅧ在血液循环中的暴露时间,减少了自身抗体的产生,以及FⅧ和自身抗体的接触机会。笔者拟就近年来靶向血小板表达FⅧ基因治疗HA的新进展进行总结。

Gene therapy can correct the coagulation disorder permanently which can be a promising alternative for hemophilia A(HA)patients.There could be different targeted cells of human for gene therapy of HA.To solve some questions of hepatocyte-targeted gene therapy,platelet-targeted gene therapy with the FⅧexpression restricted in platelets has been developed in recent years.Platelet-targeted gene therapy strategy has been developed,in which FⅧexpression is driven by various platelet-specific promoters such as platelet glycoprotein alphaⅡb promoter,glycoproteinⅠb promoter and platelet factor-4 promoter.This gene therapy strategy has been proved to have advantages in many ways.Firstly,a substantial amount of FⅧhad potent effects to promote hemostasis and activate coagulation,which were accumulated at the sites of injury or bleeding.Then,FⅧis stored in the alpha-granules of platelets,which greatly reduces the exposure time of FⅧin the blood circulation,reduces the production of autoantibodies and the opportunity for FⅧand autoantibodies.This review summarizes studies on platelet-specific gene therapy for HA in recent years.