小干扰RNA药物在慢性病领域的研究新进展:从临床前到临床  

New Research Progress of Small Interfering RNA Drugs in the Field of Chronic Diseases:from Preclinical to Clinical

作　　者：虞娇娇 蔡栅愉 俞茂承 张媛媛 罗云 陈昌买 YU Jiaojiao;CAI Shanyu;YU Maocheng;ZHANG Yuanyuan;LUO Yun;CHEN Changmai(School of Pharmacy,Fujian Medical University,Fuzhou 350122,China;ClinChoice Enterprise Management Co.,Ltd.,Shanghai 200032,China;Yaoyuan Biotechnology Co.,Ltd.,Shanghai 201613,China)

机构地区：[1]福建医科大学药学院,福建福州350122 [2]ClinChioce昆翎企业管理有限公司,上海200032 [3]曜源生物科技有限公司,上海201613

出　　处：《药学进展》2024年第8期579-591,共13页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金(No.22207017);福建省科技创新联合资金项目(No.2020Y9008)。

摘　　要：病因复杂、病程长、服药依从性和持续性差是目前慢性病治疗的“窘境”,但这也促进了慢性病治疗策略的升级迭代和创新。小干扰RNA(small interfering RNA,siRNA)药物精准靶向沉默致病基因,具备不易产生耐药性以及药效持久的优势,可以大幅减少给药频率,提高慢性病患者依从性。siRNA药物正加速被贴上“慢性病创新疗法”的标签,正加快形成创新药的“新质生产力”,有望颠覆当前的慢性病治疗模式。综述归纳整理了2018—2023年批准上市6款siRNA药物的作用机制、化学修饰、递送系统和药代动力学特征等;聚焦高血压、高脂血症、非酒精性脂肪性肝炎、慢性乙型肝炎和阿尔茨海默病等慢性病,针对在研的一系列siRNA药物进行从临床前到临床的新进展概述,以期为siRNA药物在慢性病领域的研发提供借鉴。The treatment of chronic diseases is currently hampered by complex etiology,prolonged disease progression,and poor medication compliance and persistence.However,these challenges have also spurred the improvement,iteration,and innovation of treatment strategies for chronic diseases.Small interfering RNA drugs precisely target and silence pathogenic genes with the advantages of reduced drug resistance and prolonged therapeutic efficacy,thus being able to significantly reduce the frequency of dosing and improve compliance in patients with chronic diseases.siRNA drugs,which are being increasingly labelled as"innovative treatments for chronic diseases"and accelerating the formation of a"new quality productivity"of innovative drugs,are expected to overturn the current chronic disease treatment model.This review provides an overview of the mechanism of action,chemical modifications,delivery systems,and pharmacokinetic profiles of six siRNA drugs approved for commercial use between 2018 and 2023.It focuses on chronic diseases such as hypertension,hyperlipidemia,non-alcoholic steatohepatitis,chronic hepatitis B,and Alzheimer's disease,and provides an overall review of recent advances in siRNA drug research in the field of chronic diseases,from preclinical to clinical stages of development,with the aim of providing some insight for the development of siRNA-based nucleic acid drugs in the field of chronic diseases.

关 键 词：siRNA药物 慢性病 化学修饰 药物递送系统 创新疗法 

分 类 号：Q812[生物学—生物工程]