地中海贫血基因治疗进展和现状

Progress and current status of gene therapy for thalassemia

地中海贫血(地贫)是由于α-或β-珠蛋白基因突变或者缺失使α-或β-珠蛋白链生成缺陷,最终导致的遗传性溶血性疾病。同种异体造血干细胞移植是一种能够治愈输血依赖型地贫(TDT)的选择,但由于匹配的供体来源的限制,以及不匹配供体移植的风险,只有不到10%的患者能受益于这种治疗。自体造血干细胞的基因治疗为TDT患者提供了一个新的、可治愈的选择。β-地贫的基因治疗主要有两种策略:一是通过慢病毒载体介导补充β-珠蛋白的基因替代;二是通过基因编辑技术重新激活胎儿期γ-珠蛋白的表达。α-地贫基因治疗的研究还未有报道。本文综述了β-地贫基因治疗国际和国内的进展和现状,还讨论了目前地贫基因治疗的问题和后续研发的可能方向。

Thalassemia is a hereditary hemolytic disease caused by the deficiency production of either theα-orβ-globin chains,resulting from mutation or deletion of theα-orβ-globin genes.Allogeneic hematopoietic stem cell transplantation is a curative option available for transfusion dependent thalassemia(TDT)patients.However,due to the limitation of matching donor sources,as well as the risk of unmatched donor transplantation,only fewer than 10%of patients are actually able to avail of the treatment.Gene therapy of autologous hematopoietic stem cell transplantation offers a new curative option for patients with TDT.Currently,there are two main strategies for gene therapy ofβ-thalassemia,one is through lentiviral vector mediated replacement ofβ-globin gene,and the other is through gene editing to re-active the expression of fetalγ-globin.There have been no reports about gene therapy forα-thalassemia until now.This article reviews the progress and status of gene therapy forβ-thalassemia at home and abroad,and discusses the current problems and possible future directions of follow-up research of gene therapy forβ-thalassemia.