tetano
Editor, Senior Moderator
Nucleic Acids Res
. 2022 Feb 15;gkac016.
doi: 10.1093/nar/gkac016. Online ahead of print.
Type III CRISPR-based RNA editing for programmable control of SARS-CoV-2 and human coronaviruses
Ping Lin[SUP] 1 2 [/SUP], Guanwang Shen[SUP] 1 3 [/SUP], Kai Guo[SUP] 4 [/SUP], Shugang Qin[SUP] 5 [/SUP], Qinqin Pu[SUP] 5 [/SUP], Zhihan Wang[SUP] 5 [/SUP], Pan Gao[SUP] 5 [/SUP], Zhenwei Xia[SUP] 6 [/SUP], Nadeem Khan[SUP] 5 [/SUP], Jianxin Jiang[SUP] 2 [/SUP], Qingyou Xia[SUP] 1 3 [/SUP], Min Wu[SUP] 5 [/SUP]
Affiliations
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.
. 2022 Feb 15;gkac016.
doi: 10.1093/nar/gkac016. Online ahead of print.
Type III CRISPR-based RNA editing for programmable control of SARS-CoV-2 and human coronaviruses
Ping Lin[SUP] 1 2 [/SUP], Guanwang Shen[SUP] 1 3 [/SUP], Kai Guo[SUP] 4 [/SUP], Shugang Qin[SUP] 5 [/SUP], Qinqin Pu[SUP] 5 [/SUP], Zhihan Wang[SUP] 5 [/SUP], Pan Gao[SUP] 5 [/SUP], Zhenwei Xia[SUP] 6 [/SUP], Nadeem Khan[SUP] 5 [/SUP], Jianxin Jiang[SUP] 2 [/SUP], Qingyou Xia[SUP] 1 3 [/SUP], Min Wu[SUP] 5 [/SUP]
Affiliations
- PMID: 35166837
- DOI: 10.1093/nar/gkac016
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.