Current status and trends in small nucleic acid drug development:Leading the future  

作　　者：Yuxi Miao Chen Fu Zhaojin Yu Lifeng Yu Yu Tang Minjie Wei 

机构地区：[1]Department of Pharmacology,School of Pharmacy,China Medical University,Shenyang 110122,China [2]Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation,China Medical University,Shenyang 110122,China [3]Liaoning Medical Diagnosis and Treatment Center,Shenyang 110000,China [4]Department of Oncology,Cancer Hospital of China Medical University,Liaoning Cancer Hospital and Institute,Shenyang 110042,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第9期3802-3817,共16页药学学报（英文版）

基　　金：the National Natural Science Foundation of China(NSFC,No.82272797);the National Natural Science Foundation of China(NSFC,No.82304564);Shenyang Young and Middle-aged Scientific and Technological Innovation Talents Support Project(No.RC220508,China).

摘　　要：Small nucleic acid drugs,composed of nucleotides,represent a novel class of pharmaceuticals that differ significantly from conventional small molecule and antibody-based therapeutics.These agents function by selectively targeting specific genes or their corresponding messenger RNAs(mRNAs),further modulating gene expression and regulating translation-related processes.Prominent examples within this category include antisense oligonucleotides(ASO),small interfering RNAs(siRNAs),micro-RNAs(miRNAs),and aptamers.The emergence of small nucleic acid drugs as a focal point in contemporary biopharmaceutical research is attributed to their remarkable specificity,facile design,abbreviated development cycles,expansive target spectrum,and prolonged activity.Overcoming challenges such as poor stability,immunogenicity,and permeability issues have been addressed through the integration of chemical modifications and the development of drug delivery systems.This review provides an overview of the current status and prospective trends in small nucleic acid drug development.Commencing with a historical context,we introduce the primary classifications and mechanisms of small nucleic acid drugs.Subsequently,we delve into the advantages of the U.S.Food and Drug Administration(FDA)approved drugs and mainly discuss the challenges encountered during their development.Apart from researching chemical modification and delivery system that efficiently deliver and enrich small nucleic acid drugs to target tissues,promoting endosomal escape is a critical scientific question and important research direction in siRNA drug development.Future directions in this field will prioritize addressing these challenges to facilitate the clinical transformation of small nucleic acid drugs.

关 键 词：Small nucleic acid drugs Oligonucleotide drugs siRNA ASO miRNA APTAMER RNAi Drug development 

分 类 号：R943[医药卫生—药剂学]