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从实验室到临床:RNA 疫苗和治疗在传染病中的潜力和挑战。

From bench side to clinic: Potential and challenges of RNA vaccines and therapeutics in infectious diseases.

机构信息

RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, 121001, India.

Laboratory of Synthetic Biology, Regional Centre for Biotechnology, Faridabad, 121001, India.

出版信息

Mol Aspects Med. 2021 Oct;81:101003. doi: 10.1016/j.mam.2021.101003. Epub 2021 Jul 28.

Abstract

The functional and structural versatility of Ribonucleic acids (RNAs) makes them ideal candidates for overcoming the limitations imposed by small molecule-based drugs. Hence, RNA-based biopharmaceuticals such as messenger RNA (mRNA) vaccines, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNA mimics, anti-miRNA oligonucleotides (AMOs), aptamers, riboswitches, and CRISPR-Cas9 are emerging as vital tools for the treatment and prophylaxis of many infectious diseases. Some of the major challenges to overcome in the area of RNA-based therapeutics have been the instability of single-stranded RNAs, delivery to the diseased cell, and immunogenicity. However, recent advancements in the delivery systems of in vitro transcribed mRNA and chemical modifications for protection against nucleases and reducing the toxicity of RNA have facilitated the entry of several exogenous RNAs into clinical trials. In this review, we provide an overview of RNA-based vaccines and therapeutics, their production, delivery, current advancements, and future translational potential in treating infectious diseases.

摘要

核糖核酸(RNAs)在功能和结构上的多功能性使其成为克服基于小分子药物限制的理想候选物。因此,基于 RNA 的生物制药,如信使 RNA(mRNA)疫苗、反义寡核苷酸(ASO)、小干扰 RNA(siRNA)、微 RNA 模拟物、抗微 RNA 寡核苷酸(AMO)、适体、核酶和 CRISPR-Cas9,正在成为治疗和预防许多传染病的重要工具。在 RNA 治疗领域,需要克服的主要挑战包括单链 RNA 的不稳定性、递送到病变细胞以及免疫原性。然而,体外转录 mRNA 传递系统的最新进展以及针对核酸酶的保护和降低 RNA 毒性的化学修饰,促进了几种外源性 RNA 进入临床试验。在这篇综述中,我们概述了基于 RNA 的疫苗和治疗药物,及其生产、传递、当前进展以及在治疗传染病方面的未来转化潜力。

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