血友病AAV载体基因治疗研究进展

Research Progress of AAV-Mediated Gene Therapy for Hemophilia

血友病基因治疗经过30年的持续发展,已取得长足的进步。血友病患者FVIII或FIX水平达到正常甚至治愈已成为可能。虽然在多个国家血友病基因治疗已取得显著成果,但仍然有很大的改进空间。目前临床试验中AAV是血友病基因治疗的主要载体,未来的研究将集中在完善病毒衣壳、转基因和启动子的设计上,以追求更高的转导效率、更低的免疫反应和可预测性的治疗结果。目前的研究表明,与在动物模式中近乎100%的高转导效率相比,在人类肝细胞中实现高转导效率及凝血因子的高表达仍有不足之处,需要避免蛋白质过载引起的细胞应激风险。虽然血友病基因治疗面临一定的挑战,但是随着技术的不断发展成熟,相信未来会开发出真正治愈血友病的个体化治疗方案。

Gene therapy has great potential to produce normal levels of FVIII or FIX in patients with hemophilia.After nearly 30 years of continuous development in this field,considerable progress has been made,but there is still much room for improvement.AVV is the primary carrier of gene therapy for hemophilia.Researches will focus on improving the design of viral capsids,transgenes and promoters in order to pursue higher transduction efficiency,lower immune response and predictable treatment results.Compared with the almost 100%transduction efficiency of animal models,there are still shortcomings in achieving high transduction efficiency and high expression of coagulation factors in human hepatocytes.At the same time,attention should be paid to avoid the risk of cell stress caused by protein overload.Although gene therapy for hemophilia still faces specific challenges,safer,more effective and even personalized treatment plans will be developed in the future to truly improve the quality of life of hemophilia patients and even cure them.