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siRNA在COVID-19治疗中的潜力:重点在于设计和基于纳米颗粒的递送。

Potential of siRNA in COVID-19 therapy: Emphasis on design and nanoparticles based delivery.

作者信息

Fopase Rushikesh, Panda Chinmaya, Rajendran Amarnath P, Uludag Hasan, Pandey Lalit M

机构信息

Bio-Interface & Environmental Engineering Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam, India.

Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada.

出版信息

Front Bioeng Biotechnol. 2023 Feb 6;11:1112755. doi: 10.3389/fbioe.2023.1112755. eCollection 2023.

DOI:10.3389/fbioe.2023.1112755
PMID:36814718
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9939533/
Abstract

Small interfering RNA (siRNA)-mediated mRNA degradation approach have imparted its eminence against several difficult-to-treat genetic disorders and other allied diseases. Viral outbreaks and resulting pandemics have repeatedly threatened public health and questioned human preparedness at the forefront of drug design and biomedical readiness. During the recent pandemic caused by the SARS-CoV-2, mRNA-based vaccination strategies have paved the way for a new era of RNA therapeutics. RNA Interference (RNAi) based approach using small interfering RNA may complement clinical management of the COVID-19. RNA Interference approach will primarily work by restricting the synthesis of the proteins required for viral replication, thereby hampering viral cellular entry and trafficking by targeting host as well as protein factors. Despite promising benefits, the stability of small interfering RNA in the physiological environment is of grave concern as well as site-directed targeted delivery and evasion of the immune system require immediate attention. In this regard, nanotechnology offers viable solutions for these challenges. The review highlights the potential of small interfering RNAs targeted toward specific regions of the viral genome and the features of nanoformulations necessary for the entrapment and delivery of small interfering RNAs. design of small interfering RNA for different variants of SARS-CoV-2 has been discussed. Various nanoparticles as promising carriers of small interfering RNAs along with their salient properties, including surface functionalization, are summarized. This review will help tackle the real-world challenges encountered by the delivery of small interfering RNAs, ensuring a safe, stable, and readily available drug candidate for efficient management of SARS-CoV-2 in the future.

摘要

小干扰RNA(siRNA)介导的mRNA降解方法在对抗几种难以治疗的遗传疾病和其他相关疾病方面已彰显出其卓越性。病毒爆发及由此引发的大流行一再威胁公众健康,并对药物设计和生物医学准备工作前沿的人类防范能力提出质疑。在由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的近期大流行期间,基于mRNA的疫苗接种策略为RNA治疗的新时代铺平了道路。基于小干扰RNA的RNA干扰(RNAi)方法可能会辅助新型冠状病毒肺炎(COVID-19)的临床管理。RNA干扰方法主要通过限制病毒复制所需蛋白质的合成来发挥作用,从而通过靶向宿主以及蛋白质因子来阻碍病毒的细胞进入和运输。尽管有诸多益处,但小干扰RNA在生理环境中的稳定性也备受关注,并且其定点靶向递送和免疫系统逃避问题也需要立即引起重视。在这方面,纳米技术为这些挑战提供了可行的解决方案。本综述强调了靶向病毒基因组特定区域的小干扰RNA的潜力以及包裹和递送小干扰RNA所需的纳米制剂的特性。讨论了针对SARS-CoV-2不同变体的小干扰RNA的设计。总结了各种作为小干扰RNA有前景载体的纳米颗粒及其显著特性,包括表面功能化。本综述将有助于应对小干扰RNA递送中遇到的实际挑战,确保未来有一个安全、稳定且易于获得的候选药物来有效管理SARS-CoV-2。

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