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仿生时空管理策略促进 RNA 疗法发展。

Bioinspired Spatiotemporal Management toward RNA Therapies.

机构信息

Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.

出版信息

ACS Nano. 2023 Dec 26;17(24):24539-24563. doi: 10.1021/acsnano.3c08219. Epub 2023 Dec 13.

Abstract

Ribonucleic acid (RNA)-based therapies have become an attractive topic in disease intervention, especially with some that have been approved by the FDA such as the mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech, and Spikevax, Moderna) and Patisiran (siRNA-based drug for liver delivery). However, extensive applications are still facing challenges in delivering highly negatively charged RNA to the targeted site. Therapeutic delivery strategies including RNA modifications, RNA conjugates, and RNA polyplexes and delivery platforms such as viral vectors, nanoparticle-based delivery platforms, and hydrogel-based delivery platforms as potential nucleic acid-releasing depots have been developed to enhance their cellular uptake and protect nucleic acid from being degraded by immune systems. Here, we review the growing number of viral vectors, nanoparticles, and hydrogel-based RNA delivery systems; describe RNA loading/release mechanism induced by environmental stimulations including light, heat, pH, or enzyme; discuss their physical or chemical interactions; and summarize the RNA therapeutics release period (temporal) and their target cells/organs (spatial). Finally, we describe current concerns, highlight current challenges and future perspectives of RNA-based delivery systems, and provide some possible research areas that provide opportunities for clinical translation of RNA delivery carriers.

摘要

基于核糖核酸(RNA)的疗法已成为疾病干预的一个热门话题,特别是一些已获得美国食品药品监督管理局(FDA)批准的疗法,如信使 RNA(mRNA)COVID-19 疫苗(辉瑞-BioNTech 公司的 Comirnaty 和 Moderna 公司的 Spikevax)和 Patisiran(用于肝脏递送的基于 siRNA 的药物)。然而,在将带负电荷的 RNA 递送到靶向部位方面,广泛应用仍面临挑战。为了提高其细胞摄取能力并保护核酸免受免疫系统降解,已经开发了多种治疗性递药策略,包括 RNA 修饰、RNA 缀合物、RNA 多聚物和递药平台,如病毒载体、基于纳米粒子的递药平台和基于水凝胶的递药平台,作为潜在的核酸释放库。在这里,我们综述了越来越多的病毒载体、纳米粒子和基于水凝胶的 RNA 递药系统;描述了包括光、热、pH 值或酶等环境刺激诱导的 RNA 加载/释放机制;讨论了它们的物理或化学相互作用;总结了 RNA 治疗剂的释放时间(时间)及其靶细胞/器官(空间)。最后,我们描述了当前的关注点,强调了基于 RNA 的递药系统的当前挑战和未来展望,并提供了一些可能的研究领域,为 RNA 递药载体的临床转化提供了机会。

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