小核酸药物非临床特点和药理毒理评价策略

Nonclinical features of small nucleic acid drugs and the pharmacology and toxicology evaluation strategy

通过与靶向信使RNA结合,小核酸药物能特异性地沉默疾病基因来治疗疾病。目前,已有12种小核酸药物在欧美国家上市,还有更多药物处于各个研发阶段。小核酸药物虽然来自人工合成,但因其自身特点不能单纯按照化学药物进行非临床评价。本文结合已上市药物的研究资料和相关指导原则,分别从成药性、药效学、药动学及安全性评价四方面对小核酸药物非临床特点和评价策略进行阐述。

By binding to target messenger RNAs,small nucleic acid drugs can treat some diseases by specifically interfering their genes translations.At present,12 small nucleic acid drugs have been approved in Europe and the United States,and more are in various development stages.Although synthesized chemically,they have their own characteristics,and can’t be evaluated for non-clinical features only according to chemical drugs’principle.In this paper,the non-clinical features and evaluation strategy of small nucleic acid drugs were discussed from four aspects,i.e.,druggability,pharmacodynamics,pharmacokinetics and safety evaluation,on the basis of the research data of marketed drugs and relevant guidelines.