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CRISPR-Cas13b 系统在体外降解 SARS-CoV 和 SARS-CoV-2 RNA。

A CRISPR-Cas13b System Degrades SARS-CoV and SARS-CoV-2 RNA In Vitro.

机构信息

Department of Laboratory Medicine, Unit of Clinical Microbiology, Karolinska Institutet, 17177 Stockholm, Sweden.

Biomedrex Genetics, Alfred Nobels allé 8, 14152 Stockholm, Sweden.

出版信息

Viruses. 2024 Sep 28;16(10):1539. doi: 10.3390/v16101539.

DOI:10.3390/v16101539
PMID:39459873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11512209/
Abstract

In a time of climate change, population growth, and globalization, the risk of viral spread has significantly increased. The 21st century has already witnessed outbreaks of Severe Acute Respiratory Syndrome virus (SARS-CoV), Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2), Ebola virus and Influenza virus, among others. Viruses rapidly adapt and evade human immune systems, complicating the development of effective antiviral countermeasures. Consequently, the need for novel antivirals resilient to viral mutations is urgent. In this study, we developed a CRISPR-Cas13b system to target SARS-CoV-2. Interestingly, this system was also efficient against SARS-CoV, demonstrating broad-spectrum potential. Our findings highlight CRISPR-Cas13b as a promising tool for antiviral therapeutics, underscoring its potential in RNA-virus-associated pandemic responses.

摘要

在气候变化、人口增长和全球化的时代,病毒传播的风险显著增加。21 世纪已经见证了严重急性呼吸系统综合症病毒(SARS-CoV)、严重急性呼吸系统综合症病毒 2 型(SARS-CoV-2)、埃博拉病毒和流感病毒等的爆发。病毒迅速适应并逃避人体免疫系统,这使得开发有效的抗病毒对策变得复杂。因此,迫切需要对病毒突变具有抗性的新型抗病毒药物。在这项研究中,我们开发了一种针对 SARS-CoV-2 的 CRISPR-Cas13b 系统。有趣的是,该系统对 SARS-CoV 也有效,显示出广谱潜力。我们的研究结果强调了 CRISPR-Cas13b 作为抗病毒治疗的有前途的工具,突出了其在与 RNA 病毒相关的大流行应对中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/c00ab216b59b/viruses-16-01539-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/d9969c447e17/viruses-16-01539-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/73efdecd4412/viruses-16-01539-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/a5d90181fbc2/viruses-16-01539-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/c00ab216b59b/viruses-16-01539-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/d9969c447e17/viruses-16-01539-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/73efdecd4412/viruses-16-01539-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/a5d90181fbc2/viruses-16-01539-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3e9/11512209/c00ab216b59b/viruses-16-01539-g004.jpg

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本文引用的文献

1
mRNA-encoded Cas13 treatment of Influenza via site-specific degradation of genomic RNA.通过基因组RNA的位点特异性降解进行mRNA编码的Cas13治疗流感
PLoS Pathog. 2024 Jul 5;20(7):e1012345. doi: 10.1371/journal.ppat.1012345. eCollection 2024 Jul.
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Single-base tiled screen unveils design principles of PspCas13b for potent and off-target-free RNA silencing.单碱基平铺屏幕揭示了 PspCas13b 用于有效和无脱靶 RNA 沉默的设计原理。
Nat Struct Mol Biol. 2024 Nov;31(11):1702-1716. doi: 10.1038/s41594-024-01336-0. Epub 2024 Jul 1.
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CRISPR-Cas13b-mediated suppression of HBV replication and protein expression.
CRISPR-Cas13b 介导的 HBV 复制和蛋白表达抑制。
J Hepatol. 2024 Nov;81(5):794-805. doi: 10.1016/j.jhep.2024.05.025. Epub 2024 May 28.
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Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia.社论:CRISPR-Cas9 治疗性基因编辑治疗镰状细胞病和输血依赖型β-地中海贫血的首次监管批准。
Med Sci Monit. 2024 Mar 1;30:e944204. doi: 10.12659/MSM.944204.
5
SARS-CoV-2 NSP12 utilizes various host splicing factors for replication and splicing regulation.严重急性呼吸综合征冠状病毒 2 号(SARS-CoV-2)的 NSP12 利用多种宿主剪接因子进行复制和剪接调控。
J Med Virol. 2024 Jan;96(1):e29396. doi: 10.1002/jmv.29396.
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The world's first CRISPR therapy is approved: who will receive it?世界首个CRISPR疗法获批:谁将接受该疗法?
Nat Biotechnol. 2024 Jan;42(1):3-4. doi: 10.1038/d41587-023-00016-6.
7
Targeting SARS-CoV-2 Non-Structural Proteins.靶向 SARS-CoV-2 非结构蛋白。
Int J Mol Sci. 2023 Aug 20;24(16):13002. doi: 10.3390/ijms241613002.
8
Recent Advances in Molecular Mechanisms of Nucleoside Antivirals.核苷类抗病毒药物分子机制的最新进展
Curr Issues Mol Biol. 2023 Aug 17;45(8):6851-6879. doi: 10.3390/cimb45080433.
9
The effects of length and sequence of gRNA on Cas13b and Cas13d activity in vitro and in vivo.向导RNA的长度和序列对Cas13b和Cas13d在体外和体内活性的影响。
Biotechnol J. 2023 Sep;18(9):e2300002. doi: 10.1002/biot.202300002. Epub 2023 Jul 14.
10
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