Type III CRISPR-based RNA editing for programmable control of SARS-CoV-2 and human coronaviruses. Issue 8 (15th February 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Nucleic acids research. Volume 50:Issue 8(2022)
• Page Start: e47
• Page End: e47
• Publication Date: 2022-02-15
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkac016
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: 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 T ype III CRISPR e ndonuclease a ntivir als for co ronav iruses (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.