李丹, 黄宇坤, 高小玲. RNA药物递送研究进展J. 药学学报, 2023, 58(3): 469-482. DOI: 10.16438/j.0513-4870.2022-0500
引用本文: 李丹, 黄宇坤, 高小玲. RNA药物递送研究进展J. 药学学报, 2023, 58(3): 469-482. DOI: 10.16438/j.0513-4870.2022-0500
LI Dan, HUANG Yu-kun, GAO Xiao-ling. Research progress of RNA drugs deliveryJ. Acta Pharmaceutica Sinica, 2023, 58(3): 469-482. DOI: 10.16438/j.0513-4870.2022-0500
Citation: LI Dan, HUANG Yu-kun, GAO Xiao-ling. Research progress of RNA drugs deliveryJ. Acta Pharmaceutica Sinica, 2023, 58(3): 469-482. DOI: 10.16438/j.0513-4870.2022-0500

RNA药物递送研究进展

Research progress of RNA drugs delivery

  • 摘要: 核糖核酸(ribonucleic acid, RNA) 药物可基于碱基互补配对原则, 针对目的基因的碱基序列进行设计, 精准调控基因表达, 干预遗传病、罕见病和肿瘤等多种疾病, 具备强大治疗潜力。然而, 当前RNA药物在成药性方面仍受到众多因素制约, 面临包括稳定性、半衰期、免疫原性、组织靶向性、细胞摄取和内涵体逃逸等多方面的挑战。本文介绍了近年来受到广泛关注的几种RNA药物, 主要包括信使核糖核酸(messenger RNA, mRNA)、小干扰核糖核酸(small interfering RNA, siRNA)、小分子核糖核酸(microRNA, miRNA) 和反义寡核苷酸(antisense oligonucleotide, ASO), 总结了其体内作用机制和面临的挑战, 概述了包括化学修饰、配体偶联、纳米载体在内的多种克服RNA体内递送瓶颈的递送策略; 从制备及应用等方面, 详述了RNA纳米递送载体中的脂质纳米粒、高分子聚合物载体及外泌体。本文旨在为发展高效安全的体内RNA递送技术提供理论依据和设计思路, 促进RNA药物临床转化。

     

    Abstract: Ribonucleic acid (RNA) medicines have strong therapeutic potential for numerous rare genetic illnesses and malignancies because of its exact programmability based on Watson-Crick base pairing principle and unique ability to regulate gene expression. However, RNA medicines still have limitations in many areas, including stability, half-life time, immunogenicity, organ selectivity, cellular uptake and endosomal escape efficiency despite their great therapeutic potentials. This review briefly introduced numerous RNA medications mostly messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) and antisense oligonucleotide (ASO) that have intrigued of researchers in recent years, as well as their action mechanism in vivo. A number of delivery techniques, such as chemical modification, ligands coupling and nanocarriers have been proposed. The manufacture and applications of lipid nanoparticle, polymer nanoparticle and exosomes were discussed in depth. The goal of this work is to give a theoretical foundation and design concepts for the development of effective and safe RNA delivery technology, as well as to facilitate RNA therapeutic clinical translation.

     

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