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

IF 14.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI:10.1016/j.apsb.2024.05.008
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Abstract

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.

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小核酸药物开发的现状和趋势:引领未来
由核苷酸组成的小核酸药物是一类新型药物,与传统的小分子和抗体疗法有很大不同。这些药物的功能是选择性地靶向特定基因或其相应的信使核糖核酸(mRNA),进一步调节基因表达和翻译相关过程。这类药物的突出例子包括反义寡核苷酸 (ASO)、小干扰 RNA (siRNA)、微 RNA (miRNA) 和适配体。小核酸药物之所以成为当代生物制药研究的焦点,是因为它们具有显著的特异性、易于设计、开发周期短、靶谱广和活性长等特点。为了克服稳定性差、免疫原性和渗透性等难题,人们通过整合化学修饰和开发给药系统来加以解决。本综述概述了小核酸药物开发的现状和未来趋势。从历史背景开始,我们介绍了小核酸药物的主要分类和机制。随后,我们深入探讨了美国食品和药物管理局(FDA)批准的药物的优势,并主要讨论了这些药物在开发过程中遇到的挑战。除了研究能将小核酸药物高效递送和富集到靶组织的化学修饰和递送系统外,促进内体逸出是 siRNA 药物开发的关键科学问题和重要研究方向。该领域未来的发展方向将优先解决这些挑战,以促进小核酸药物的临床转化。
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来源期刊
Acta Pharmaceutica Sinica. B
Acta Pharmaceutica Sinica. B Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
22.40
自引率
5.50%
发文量
1051
审稿时长
19 weeks
期刊介绍: The Journal of the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association oversees the peer review process for Acta Pharmaceutica Sinica. B (APSB). Published monthly in English, APSB is dedicated to disseminating significant original research articles, rapid communications, and high-quality reviews that highlight recent advances across various pharmaceutical sciences domains. These encompass pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis, and pharmacokinetics. A part of the Acta Pharmaceutica Sinica series, established in 1953 and indexed in prominent databases like Chemical Abstracts, Index Medicus, SciFinder Scholar, Biological Abstracts, International Pharmaceutical Abstracts, Cambridge Scientific Abstracts, and Current Bibliography on Science and Technology, APSB is sponsored by the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Chinese Pharmaceutical Association. Its production and hosting are facilitated by Elsevier B.V. This collaborative effort ensures APSB's commitment to delivering valuable contributions to the pharmaceutical sciences community.
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