反义药物作用机制及化学修饰研究进展

Research progress in antisense drug mechanism and chemical modification strategies

在过去的30年里,越来越多的反义药物获批上市或进入临床,反义技术凭借其在治疗疾病方面独特的优势和在临床上较强的发展潜力,已成为新药研究领域的焦点。与传统的化药小分子及大分子蛋白生物药物存在较大差异,是一种非常独立的药物形式,起源于用于治疗单基因突变的疾病,但近期逐渐开始用于常见病的治疗。因此,基于遗传学的基础合理进行反义药物设计对于疾病的治疗至关重要。本文针对当前反义药物的作用机制、化学修饰、递送策略领域的最新进展进行了阐述,并对目前存在的瓶颈问题进行了分析,相信伴随着这些问题的解决,反义药物的研究可以到达一个新的高度。

Over the past three decades,more and more antisense drugs have been approved for marketing or clinical trails.Antisense technology has become the focus of pharmaceutical research due to its unique advantages in treating diseases and strong clinical development potential.There is a big difference from traditional small molecule chemical drugs,and macromolecular protein biological drugs.Antisense drugs are a very independent drug form.Antisense drugs were initially used to treat diseases with single gene mutations,but recently they have gradually begun to be used for the treatment of common diseases.Rational antisense drug design is crucial for disease treatment based on genetics.This paper reviews the latest progress in the field of action mechanism,chemical modification and delivery strategy of antisense drugs,and analyzes the current intractable problems.It is believed that with the resolution of these problems,the research of antisense drugs can reach a new level.