USH2A基因外显子13相关遗传性视网膜变性基因治疗进展  

Advances on gene therapy for USH2A exon 13 related inherited retinal dystrophy

作　　者：李五一[1] 睢瑞芳[1] Li Wuyi;Sui Ruifang(Department of Ophthalmology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院,北京协和医院眼科,北京100730

出　　处：《中华眼科杂志》2023年第12期1058-1064,共7页Chinese Journal of Ophthalmology

基　　金：国家自然科学基金(82171086);中国医学科学院医学与健康科技创新工程(2021-I2M-1-003)。

摘　　要：USH2A基因双等位基因致病变异可导致Usher综合征Ⅱ型和非综合征性视网膜色素变性,患者因光感受器细胞进行性丧失最终失明。USH2A基因很大,其cDNA有15,606 bp,无法使用腺相关病毒载体递送进行基因替代治疗。研究发现位于外显子13的致病变异在USH2A基因所有外显子的致病变异中占比最高,成为治疗的靶点。反义寡核苷酸、基因组编辑和RNA编辑方法对USH2A基因外显子13的干预研究,显示了潜在的治疗效果和应用前景。本文总结了USH2A基因外显子13相关的分子遗传机制、研究结果以及面临的挑战。Biallelic pathogenic variants in the USH2A gene result in Usher syndrome typeⅡand non-syndromic retinitis pigmentosa,both of which entail the progressive loss of photoreceptors leading to blindness.The cDNA of the USH2A gene is extensive,consisting of 15606 base pairs,rendering it impractical for delivery via adeno-associated virus vectors for gene replacement therapy.Notably,exon 13 has emerged as a focal point for therapeutic intervention,given its predilection for harboring the most pathogenic variants within USH2A.Recent intervention studies targeting USH2A exon 13 through the utilization of antisense oligonucleotides,genome editing,and RNA editing approaches have exhibited promising therapeutic potential.This paper provides a comprehensive overview of the molecular mechanisms,outcome data,and the challenges associated with the application of these interventions in this domain.

关 键 词：USHER综合征 USH2A基因 外显子 基因治疗 

分 类 号：R774.1[医药卫生—眼科]