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

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 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.

• Authors: Ping Lin, Guanwang Shen, Kai Guo, Shugang Qin, Qinqin Pu, Zhihan Wang, Pan Gao, Zhenwei Xia, Nadeem Khan, Jianxin Jiang, Qingyou Xia, Min Wu
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 50 Issue 8 Pg. e47 (May 06 2022) ISSN: 1362-4962 [Electronic] England
• PMID: 35166837 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chemical References

• Antiviral Agents
• RNA, Guide, CRISPR-Cas Systems

Topics

• Animals
• Antiviral Agents
• COVID-19 (therapy)
• Humans
• Mice
• Pandemics (prevention & control)
• RNA Editing (genetics)
• RNA, Guide, CRISPR-Cas Systems (genetics)
• SARS-CoV-2 (genetics)