血友病A基因治疗及其进展

Gene Therapy of Hemophilia A and Its Progression

血友病A(HA)是基因缺陷导致凝血因子Ⅷ减少,引起机体凝血功能障碍并最终导致机体出血不止的一种遗传性疾病。目前预防治疗是我国HA的主要治疗方案,如使用凝血酶原复合物或补充凝血因子制剂,但长期使用机体易产生抗体(即抑制物),为HA的严重并发症。HA是单基因疾病,较适用于基因治疗,病毒载体的选择(逆转录病毒载体、腺相关病毒载体、慢病毒载体等)和靶细胞的选择(通过几种靶细胞,如肝窦内皮细胞、肠上皮细胞、血源内皮细胞、诱导的多能干细胞、脂肪干细胞等介导)均可影响HA基因治疗的效果。

Hemophilia A（HA） is a hereditary disease caused by the deficiency of blood coagulation factor Ⅷ due to genetic defects, resulting in coagulation disorders in the body and finally leading to hemorrhage in the body. At present, prophylaxis treatments are the main treatment programs for hemophilia in China, such as the use of prothrombin or supplement of clotting factor preparations. However,the body is easy to produce antibodies（ i. e. inhibitors） after long-term use, which is a serious complication of HA. HA is a monogenie disease that is more suitable for gene therapy, and the selection of viral veetors（retroviral vectors, adeno-assoeiated virus vectors, lentiviral vectors, etc. ） and the selection of target cells （mediated by several target cells, such as sinusoidal endothelial cells, intestinal epithelial cells, blood-derived endothelial cells, induced pluripotent stem cells, adipose-derived stem cells,etc. ） can both affect the effect of HA gene therapy.