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ENGLISH ABSTRACT
反义寡核苷酸技术在遗传性视网膜变性治疗中的应用
李五一
睢瑞芳 [综述]
作者及单位信息
·
DOI： 10.3760/cma.j.cn115989-20210128-00074
Application of antisense oligonucleotide in the treatment of inherited retinal dystrophy
Li Wuyi
Sui Ruifang
Authors Info & Affiliations
Li Wuyi
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Sui Ruifang
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
·
DOI： 10.3760/cma.j.cn115989-20210128-00074
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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。

反义寡核苷酸;基因治疗;视网膜变性，遗传性
ABSTRACT

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.

Oligonucleotides, antisense;Genetic therapy;Retinal dystrophies, inherited
Sui Ruifang, Email: mocdef.3ab61iusfrh
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引用本文

李五一,睢瑞芳. 反义寡核苷酸技术在遗传性视网膜变性治疗中的应用[J]. 中华实验眼科杂志,2022,40(01)：67-72.

DOI:10.3760/cma.j.cn115989-20210128-00074

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长期以来，遗传性视网膜变性缺乏有效的临床治疗手段。近20年中，以腺相关病毒(adeno-associated virus，AAV)和慢病毒为载体的基因增补策略在遗传性视网膜变性治疗研究中已取得重大进展，为遗传性视网膜变性治疗带来了希望，但由于载体的负载基因长度存在局限性，使其难以广泛应用。反义寡核苷酸(antisense oligonucleotide，AON)是一种通过碱基互补配对原则结合并降解靶信使RNA(messenger RNA，mRNA)以纠正或抑制其转录与翻译的小分子化合物。AON具有特异性高、微量高效、免疫原性低、毒性及不良反应小、应用范围广等优点，可以有效地填补遗传性视网膜变性基因治疗的空白。AON已在遗传性视网膜变性和视神经萎缩等眼部疾病治疗研究中取得了一定的进展，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。
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睢瑞芳，Email： mocdef.3ab61iusfrh
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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)
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