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基于CRISPR/Cas13的抗RNA病毒方法。

CRISPR/Cas13-Based Anti-RNA Viral Approaches.

作者信息

Tan Xiaoying, Li Juncong, Cui Baolong, Wu Jingjing, Toischer Karl, Hasenfuß Gerd, Xu Xingbo

机构信息

German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Robert-Koch-Str. 42a, 37075 Göttingen, Germany.

Clinic for Cardiology and Pulmonology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.

出版信息

Genes (Basel). 2025 Jul 25;16(8):875. doi: 10.3390/genes16080875.

Abstract

RNA viruses pose significant threats to global health, causing diseases such as COVID-19, HIV/AIDS, influenza, and dengue. These viruses are characterized by high mutation rates, rapid evolution, and the ability to evade traditional antiviral therapies, making effective treatment and prevention particularly challenging. In recent years, CRISPR/Cas13 has emerged as a promising antiviral tool due to its ability to specifically target and degrade viral RNA. Unlike conventional antiviral strategies, Cas13 functions at the RNA level, providing a broad-spectrum and programmable approach to combating RNA viruses. Its flexibility allows for rapid adaptation of guide RNAs to counteract emerging viral variants, making it particularly suitable for highly diverse viruses such as SARS-CoV-2 and HIV. This review discusses up-to-date applications of Cas13 in targeting a wide range of RNA viruses, including SARS-CoV-2, HIV, dengue, influenza, and other RNA viruses, focusing on its therapeutic potential. Preclinical studies have demonstrated Cas13's efficacy in degrading viral RNA and inhibiting replication, with applications spanning prophylactic interventions to post-infection treatments. However, challenges such as collateral cleavage, inefficient delivery, potential immunogenicity, and the development of an appropriate ethical framework must be addressed before clinical translation. Future research should focus on optimizing crRNA design, improving delivery systems, and conducting rigorous preclinical evaluations to enhance specificity, safety, and therapeutic efficacy. With continued advancements, Cas13 holds great promise as a revolutionary antiviral strategy, offering novel solutions to combat some of the world's most persistent viral threats.

摘要

RNA病毒对全球健康构成重大威胁,引发了如COVID-19、艾滋病毒/艾滋病、流感和登革热等疾病。这些病毒的特点是突变率高、进化迅速,且能够逃避传统的抗病毒疗法,这使得有效的治疗和预防极具挑战性。近年来,CRISPR/Cas13因其能够特异性靶向和降解病毒RNA而成为一种有前景的抗病毒工具。与传统的抗病毒策略不同,Cas13在RNA水平上发挥作用,为对抗RNA病毒提供了一种广谱且可编程的方法。其灵活性允许快速调整引导RNA以对抗新出现的病毒变体,这使其特别适用于如SARS-CoV-2和艾滋病毒等高度多样化的病毒。本文综述了Cas13在靶向多种RNA病毒(包括SARS-CoV-2、艾滋病毒、登革热、流感和其他RNA病毒)方面的最新应用,重点关注其治疗潜力。临床前研究已证明Cas13在降解病毒RNA和抑制复制方面的有效性,其应用涵盖了从预防性干预到感染后治疗。然而,在临床转化之前,必须解决诸如附带切割、递送效率低下、潜在的免疫原性以及建立适当的伦理框架等挑战。未来的研究应专注于优化crRNA设计;改进递送系统,并进行严格的临床前评估,以提高特异性、安全性和治疗效果。随着不断进步,Cas13作为一种革命性的抗病毒策略具有巨大潜力,为对抗一些全球最持久的病毒威胁提供了新的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38c5/12385312/cd7d9fc9f3f7/genes-16-00875-g001.jpg

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