反义寡核苷酸技术在遗传性视网膜变性治疗中的应用  

Application of antisense oligonucleotide in the treatment of inherited retinal dystrophy

作　　者：李五一(综述)[1] 睢瑞芳(审校)[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,北京协和医学院,北京协和医院眼科,100730

出　　处：《中华实验眼科杂志》2022年第1期67-72,共6页Chinese Journal Of Experimental Ophthalmology

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

摘　　要：遗传性视网膜变性在临床上缺乏有效的治疗手段,基因治疗有望从根本上恢复遗传物质的功能,为其提供新的治疗策略。反义寡核苷酸(AON)是一种小分子核酸类药物,可以通过碱基互补配对原则与信使RNA特异性结合,从而在转录和翻译水平干扰或恢复基因表达。AON具有特异性高、微量高效、靶向范围广、免疫原性低、毒性及不良反应小等优势,成为遗传性眼病治疗新手段。目前,已有3种不同的AON药物进入了遗传性视网膜变性疾病的临床试验阶段。本文就近年来AON在其化学结构修饰、特性和作用机制等方面的进展及其目前在不同遗传性视网膜变性疾病中应用的治疗策略进行综述。Gene therapy is expected to restore the function of genetic material fundamentally and it has become a new trend in inherited retinal dystrophy treatment.Antisense oligonucleotide(AON)is a kind of small molecule nucleic acid drug,which can specifically bind to messenger RNA through the base pairing principle,thus interfering or modifying gene expression at the transcription and translation level.Possessing the advantages of high specificity and efficiency,wide targeting range,low immunogenicity and limited adverse effect,AON has become a novel remedy for inherited retinal dystrophy.Currently,three different AON drugs have already been used in clinical trials for inherited retinal dystrophy.In this review,the chemical structure modification,properties and mechanism of AON,and the therapeutic strategies of AON in different inherited retinal dystrophy diseases in recent years were summarized.

关 键 词：反义寡核苷酸 基因治疗 视网膜变性 遗传性 

分 类 号：R774.1[医药卫生—眼科]