Shi Qizhen
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, USA.
Mol Ther Methods Clin Dev. 2018 Feb 7;9:100-108. doi: 10.1016/j.omtm.2018.01.011. eCollection 2018 Jun 15.
Gene therapy is an attractive approach for disease treatment. Since platelets are abundant cells circulating in blood with the distinctive abilities of storage and delivery and fundamental roles in hemostasis and immunity, they could be a unique target for gene therapy of diseases. Recent studies have demonstrated that ectopic expression of factor VIII (FVIII) in platelets under control of the platelet-specific promoter results in FVIII storage together with its carrier protein von Willebrand factor (VWF) in α-granules and the phenotypic correction of hemophilia A. Importantly, the storage and sequestration of FVIII in platelets appears to effectively restore hemostasis even in the presence of functional-blocking inhibitory antibodies. This review summarizes studies on platelet-specific gene therapy of hemophilia A as well as hemophilia B.
基因治疗是一种颇具吸引力的疾病治疗方法。由于血小板是血液中循环的丰富细胞，具有独特的储存和递送能力，且在止血和免疫中发挥着重要作用，它们可能成为疾病基因治疗的独特靶点。最近的研究表明，在血小板特异性启动子的控制下，血小板中因子VIII（FVIII）的异位表达导致FVIII与其载体蛋白血管性血友病因子（VWF）一起储存在α颗粒中，并对A型血友病进行表型校正。重要的是，即使存在功能阻断抑制性抗体，FVIII在血小板中的储存和隔离似乎也能有效恢复止血功能。本综述总结了关于A型血友病以及B型血友病的血小板特异性基因治疗的研究。
