摘要遗传性视网膜疾病(IRDs)属于难治性眼科疾病,基因疗法正在成为一种治疗IRDs的新方法.目前至少有26个相关的基因疗法临床试验正在进行或将要开展,至少涉及不同类型IRDs的16个突变基因,如常染色体隐性遗传的视网膜色素变性(RP,MERTK突变)、无脉络膜症(CHM突变)、青少年黄斑变性(ABCA4突变)、Usher综合征1B亚型(Myo7a突变)、X性连锁先天性视网膜劈裂症(RS1突变)、线粒体相关Leber遗传性视神经病变(ND4突变)、全色盲(CNGA3突变和CNGB3突变)、性连锁遗传RP(RPGR突变)等.新生血管性年龄相关性黄斑病变的基因治疗以及适用于晚期RP患者的、利用异种成视力基因再造感光细胞的光遗传基因治疗也已进入临床试验阶段.采用腺相关病毒(AAV)介导的基因载体治疗对由较小基因突变造成的隐性IRDs,特别是原发病灶在视网膜色素上皮(RPE)细胞和视细胞的IRDs具有较好的疗效,有可能成为将来的首选治疗方案.关于针对常染色体显性遗传性IRDs或较大基因突变引起的隐性IRDs的基因编辑技术动物实验研究也取得了进展,即将进入临床试验阶段.近年来,以RNA治疗为基础的寡核苷酸疗法对目前不适于AAV载体基因治疗的大基因突变所致IRDs也显示出较好的疗效.相关疗法的临床研究值得关注,应用不同生物疗法造福于中国IRDs患者的新时代正在到来.

abstractsInherited retinal diseases ( IRDs) are rare and incurable eye diseases. Gene therapy has become a new method for the treatment of IRDs. At present, at least 26 clinical trials of gene therapy involving at least 16 different IRDs genes are in progress or imminent. Such as autosomal recessive retinitis pigmentosa ( RP, MERTK mutation),choroideremia (CHM mutation),Stargardt' s disease (ABCA4 mutation),Usher syndrome 1B subtype (Myo7a mutation),X-linked retinoschisis (RS1 mutation),mitochondrial-related Leber hereditary optic neuropathy ( ND4 mutation ) , panchromatic blindness ( CNGA3 mutation and CNNGB3 mutation ) , sex-linked RP ( RPGR mutation) . Adeno-associated viral ( AAV ) vector-mediated gene expression is a conventional method for gene transduction,which has showed efficacies in autosomal recessive IRDs caused by small gene mutations,especially for those IRDs,which have the original lesions in retinal pigment epithelial ( RPE) cells and photoreceptor cells. Novel progress has been made in animal experiments by gene editing technologies for autosomal dominant IRDs or autosomal recessive IRDs with large gene mutations,which is going to clinical trial. Oligonucleotide therapy based on RNA has also shown good efficacy for the IRDs caused by large genes, which beyond the AAV capacity. These research achievements are attacking more and more attentions in these fields. Although there are still some efficacy and safety issues on the way to treat IRDs,it is reasonable to expect that more and more patients with IRDs will be treated in the near future.