Ionis Pharmaceuticals, Carlsbad, California 92010; email:
Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:81-105. doi: 10.1146/annurev-pharmtox-010716-104846. Epub 2016 Oct 10.
Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms by which antisense oligonucleotides can be used to modulate RNAs in cells, including promoting the degradation of the targeted RNA or modulating RNA function without degradation. Antisense drugs utilizing various antisense mechanisms are demonstrating therapeutic potential for the treatment of a broad variety of diseases. This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.
最近的研究使人们更加认识到 RNA 在维持正常细胞功能中的多种作用，以及它们如何导致疾病病理，从而扩大了潜在治疗靶点的数量。反义寡核苷酸是选择性靶向 RNA 的最直接手段，已成为药物发现的成熟平台技术。反义寡核苷酸有多种分子机制可用于在细胞中调节 RNA，包括促进靶向 RNA 的降解或在不降解的情况下调节 RNA 功能。利用各种反义机制的反义药物在治疗多种疾病方面显示出治疗潜力。本综述重点介绍了将反义技术从实验室转化到临床应用中所取得的一些进展。
