摘要
RNA药物能够通过识别互补序列靶向对应基因以抑制特定蛋白或RNA的表达,或通过翻译合成目的基因编码的蛋白来发挥遗传性疾病治疗作用。RNA药物主要分为寡核苷酸药物(包括反义寡核苷酸、小干扰RNA和RNA适配体)和信使RNA药物等。其中,反义寡核苷酸和小干扰RNA已用于临床治疗遗传病,而RNA适配体和信使RNA药物目前还处于临床试验阶段。当前主要通过对RNA药物进行化学修饰(如对信使RNA进行假尿嘧啶修饰)来降低免疫原性和提升药物疗效,以及开发纳米粒载体、细胞外囊泡和类病毒载体等递送载体来解决RNA药物的稳定性、特异靶向性和安全性等问题。本文概述了目前用于治疗遗传病的11种RNA药物的具体作用分子机制,并简单讨论了RNA药物的化学修饰及递送载体的研究现状。
RNA therapeutics inhibit the expression of specific proteins/RNAs by targeting complementary sequences of corresponding genes or encode proteins for the synthesis desired genes to treat genetic diseases.RNA-based therapeutics are categorized as oligonucleotide drugs(antisense oligonucleotides,small interfering RNA,RNA aptamers),and mRNA drugs.The antisense oligonucleotides and small interfering RNA for treatment of genetic diseases have been approved by the FDA in the United States,while RNA aptamers and mRNA drugs are still in clinical trials.Chemical modifications can be applied to RNA drugs,such as pseudouridine modification of mRNA,to reduce immunogenicity and improve the efficacy.The secure and effective delivery systems such as lipid-based nanoparticles,extracellular vesicles,and virus-like particles are under development to address stability,specificity,and safety issues of RNA drugs.This article provides an overview of the specific molecular mechanisms of eleven RNA drugs currently used for treating genetic diseases,and discusses the research progress of chemical modifications and delivery systems of RNA drugs.
作者
罗婷
霍春晓
周天华
谢珊珊
LUO Ting;HUO Chunxiao;ZHOU Tianhua;XIE Shanshan(Department of Cell Biology,Zhejiang University School of Medicine,Hangzhou 310058,China;The Fourth Affiliated Hospital,Zhejiang University School of Medicine,Center for RNA Medicine,International Institutes of Medicine,Zhejiang University,Jinhua 322000,Zhejiang Province,China;Zhejiang University Cancer Center,Hangzhou 310058,China;Children’s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China)
出处
《浙江大学学报（医学版）》
CAS
CSCD
北大核心
2023年第4期406-416,共11页
Journal of Zhejiang University(Medical Sciences)
基金
国家自然科学基金(32270723)。
作者简介
第一作者:罗婷,博士研究生,主要从事原发性纤毛运动障碍相关疾病的研究,E-mail:tingluo1117@163.com,https://orcid.org/0009-0008-8319-7000;通信作者:周天华,教授,博士生导师,主要从事分子细胞生物学相关研究,E-mail:tzhou@zju.edu.cn,https://orcid.org/0000-0002-1791-2124;通信作者:谢珊珊,研究员,硕士生导师,主要从事纤毛的功能和机制研究,E-mail:sxie@zju.edu.cn,https://orcid.org/0000-0003-4294-8169。
