Type III CRISPR-based RNA editing for programmable control of SARS-CoV-2 and human coronaviruses

Gene-editing technologies, including the widespread usage of CRISPR endonucleases, have the potential for clinical treatments of various human diseases. Due to the rapid mutations of SARS-CoV-2, specific and effective prevention and treatment by CRISPR toolkits for coronavirus disease 2019 (COVID-19...

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Bibliographic Details
Published in:Nucleic acids research 2022-05, Vol.50 (8), p.e47-e47
Main Authors: Lin, Ping, Shen, Guanwang, Guo, Kai, Qin, Shugang, Pu, Qinqin, Wang, Zhihan, Gao, Pan, Xia, Zhenwei, Khan, Nadeem, Jiang, Jianxin, Xia, Qingyou, Wu, Min
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents
COVID-19 - therapy
Humans
Methods Online
Mice
Pandemics - prevention & control
RNA Editing - genetics
RNA, Guide, CRISPR-Cas Systems - genetics
SARS-CoV-2 - genetics
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Summary:Gene-editing technologies, including the widespread usage of CRISPR endonucleases, have the potential for clinical treatments of various human diseases. Due to the rapid mutations of SARS-CoV-2, specific and effective prevention and treatment by CRISPR toolkits for coronavirus disease 2019 (COVID-19) are urgently needed to control the current pandemic spread. Here, we designed Type III CRISPR endonuclease antivirals for coronaviruses (TEAR-CoV) as a therapeutic to combat SARS-CoV-2 infection. We provided a proof of principle demonstration that TEAR-CoV-based RNA engineering approach leads to RNA-guided transcript degradation both in vitro and in eukaryotic cells, which could be used to broadly target RNA viruses. We report that TEAR-CoV not only cleaves SARS-CoV-2 genome and mRNA transcripts, but also degrades live influenza A virus (IAV), impeding viral replication in cells and in mice. Moreover, bioinformatics screening of gRNAs along RNA sequences reveals that a group of five gRNAs (hCoV-gRNAs) could potentially target 99.98% of human coronaviruses. TEAR-CoV also exerted specific targeting and cleavage of common human coronaviruses. The fast design and broad targeting of TEAR-CoV may represent a versatile antiviral approach for SARS-CoV-2 or potentially other emerging human coronaviruses.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkac016