反义寡核苷酸治疗Duchenne型肌营养不良的研究进展

Duchenne型肌营养不良(DMD)是由抗肌萎缩蛋白基因Dystrophin发生移码突变导致的儿童遗传性致死性肌病。反义寡核苷酸(AON)靶向外显子中的剪接调控序列可以诱导Dystrophin基因的相应外显子跳读，以恢复dystrophin mRNA阅读框，是目前新的DMD治疗方法。该治疗方法的有效性已在患者来源的肌细胞及动物模型中得到证实。目前，AON靶向治疗DMD已经进入药物临床试验阶段。笔者拟对DMD的分子致病机制、AON治疗DMD的作用机制及其临床试验新进展进行综述，为AON在DMD治疗中的临床应用提供理论依据。

Research progress of antisense oligonucleotide on treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is lethal inherited muscular disorder which caused by frame-shift mutations in the Dystrophin gene. The splicing regulatory sequence in target exon of antisense oligonucleotide (AON) can induce exon skipping to re-framing the dystrophin mRNA.It is a new therapy strategy to treat DMD, and the applicability of AON has been confirmed in both patient-derived muscle cell cultures and animals models. Currently, AON medication for DMD are in clinical trials.This paper reviews the molecular basis of DMD, the mechanisms of AON action and the progress of AON therapy in clinical trials, in order to provide theoretical basis for clinical application of AON medication.