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

被引：7
作者：
Miao, Yuxi [1 ,2 ,3 ]
Fu, Chen [1 ,2 ]
Yu, Zhaojin [1 ,2 ]
Yu, Lifeng [1 ]
Tang, Yu [4 ]
Wei, Minjie [1 ,2 ,3 ]
机构：
[1] China Med Univ, Sch Pharm, Dept Pharmacol, Shenyang 110122, Peoples R China
[2] China Med Univ, Liaoning Key Lab Mol Targeted Antitumor Drug Dev &, Shenyang 110122, Peoples R China
[3] Liaoning Med Diag & Treatment Ctr, Shenyang 110000, Peoples R China
[4] China Med Univ, Liaoning Canc Hosp & Inst, Dept Oncol, Canc Hosp, Shenyang 110042, Peoples R China
来源：
ACTA PHARMACEUTICA SINICA B | 2024年 / 14卷 / 09期
基金：
中国国家自然科学基金;
关键词：
Small nucleic acid drugs; Oligonucleotide drugs; siRNA; ASO; miRNA; Aptamer; RNAi; Drug development; RNA-DERIVED FRAGMENTS; ANTISENSE OLIGONUCLEOTIDES; DELIVERY-SYSTEMS; GENE-EXPRESSION; C-ELEGANS; THERAPEUTICS; INTERFERENCE; COMPLEX; TARGETS; COMPLEMENTARITY;
D O I：
10.1016/j.apsb.2024.05.008
中图分类号：
R9 [药学];
学科分类号：
1007 ;
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), microRNAs (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.
引用
收藏
页码：3802 / 3817
页数：16
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