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 selective...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.展开更多
目的了解全球小核酸药物发展态势,为我国小核酸药物研发提供参考。方法通过Web of Science文献数据库和智慧芽专利数据库检索1980年1月-2021年12月发表/申请的小核酸药物相关学术文献/专利,对小核酸药物的研究热度、研发国家、研发机构...目的了解全球小核酸药物发展态势,为我国小核酸药物研发提供参考。方法通过Web of Science文献数据库和智慧芽专利数据库检索1980年1月-2021年12月发表/申请的小核酸药物相关学术文献/专利,对小核酸药物的研究热度、研发国家、研发机构和技术主题等进行分析。结果与结论共纳入文献59819篇、专利37645组。全球小核酸药物文献发表与专利申请趋势可分为3个阶段,小核酸药物的研究热度在2003-2021年不断增强。美国、中国、日本、德国是小核酸药物主要的研发国家,美国与中国的文献发表量(25703、15927篇)和专利申请量(14240、8937组)领先于其他各国,研发活跃度较强,且中国在该领域近年来文献发表量和专利申请量增速较快。文献发表量最多的研发机构是美国加利福尼亚大学(2499篇),专利申请量最多的研发机构是美国Ionis公司(1378组),中国科学院(文献发表量为1580篇)已经入围全球前10位文献产出机构;但我国在该领域的研发更多停留在基础研究上,在产业应用方面的研究稍显不足。小核酸药物领域的研究重心主要集中在核酸序列及其修饰改进和载药技术上,RNA干扰技术已逐渐成为小核酸药物的热点技术。展开更多
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).
文摘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.
文摘目的了解全球小核酸药物发展态势,为我国小核酸药物研发提供参考。方法通过Web of Science文献数据库和智慧芽专利数据库检索1980年1月-2021年12月发表/申请的小核酸药物相关学术文献/专利,对小核酸药物的研究热度、研发国家、研发机构和技术主题等进行分析。结果与结论共纳入文献59819篇、专利37645组。全球小核酸药物文献发表与专利申请趋势可分为3个阶段,小核酸药物的研究热度在2003-2021年不断增强。美国、中国、日本、德国是小核酸药物主要的研发国家,美国与中国的文献发表量(25703、15927篇)和专利申请量(14240、8937组)领先于其他各国,研发活跃度较强,且中国在该领域近年来文献发表量和专利申请量增速较快。文献发表量最多的研发机构是美国加利福尼亚大学(2499篇),专利申请量最多的研发机构是美国Ionis公司(1378组),中国科学院(文献发表量为1580篇)已经入围全球前10位文献产出机构;但我国在该领域的研发更多停留在基础研究上,在产业应用方面的研究稍显不足。小核酸药物领域的研究重心主要集中在核酸序列及其修饰改进和载药技术上,RNA干扰技术已逐渐成为小核酸药物的热点技术。
