摘要
单链寡核苷酸(single-stranded oligonucleotide,SSO)是一种人工合成寡核苷酸,可按碱基互补配对原则主要通过与靶RNA杂交,诱导断裂、调节剪切、抑制翻译等作用抑制靶RNA功能。未经修饰的SSO易被核酸酶降解,经化学修饰的SSO(如经锁核酸修饰后的SSO)其稳定性、杂交亲和力及酶切效率大大提高,成药性显著增强。目前,已有4个治疗用SSO药物在美国或欧洲上市,更多的候选药物处于研发阶段。本文从监管、非临床特点、非临床安全性试验一般原则等方面阐述治疗用SSO药物的非临床研究评价要点。
Single-stranded oligonucleotide(SSO） is a synthetic oligonucleotide,which can hybride with the targeting RNA via base-pairing,thus inducing break,adjusting shearing,suppressing translation,in turn producing potential therapeutic effects at the gene level. However,the un-modified SSO can be degraded easily by DNA enzymes while the chemically-modified SSO,for example,LNA-modified SSO,has shown great drugablity as its stability,affinity of hybridation,and enzyme shearing ability have been improved. Currently,there are four SSOs approved for therapeutic purpose in US/EU and more are on the way. This article discusses the considerations of the preclinical evaluation of therapeutic SSOs from the aspects of regulation,nonclinical profiles and general principles of nonclinical safety studies.
作者
余珊珊
胡晓敏
王海学
王旸
王庆利
YU Shan-shan;HU Xiao-min;WANG Hai-xue;WANG Yang;WANG Qing-li(Center for Drug Evaluation, China Food and Drug Administration, Beijing 100038, China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2018年第10期1122-1129,共8页
Chinese Journal of New Drugs
关键词
治疗用单链寡核苷酸药物
锁核酸
非临床研究评价
therapeutic single-stranded oligonucleotides drug
locked nucleic acids
nonclinical study and evaluation
