Journal
NUCLEIC ACIDS RESEARCH
Volume 50, Issue 8, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac016
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Funding
- NationalNature Science Foundation of China [32000033, 82020108021, 32030103]
- Natural Science Foundation of Chongqing [cstc2020jcyj-cxttX0001]
- National Institutes of Health [R01AI109317-01A1, R01 AI138203, P20 GM113123, P20 GM103442]
- UND Post-Doc Pilot Grant
- American Association of Immunologists
- National Nature Science Foundation of China
- National Institutes ofHealth Grants
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The study developed a CRISPR endonuclease antiviral called TEAR-CoV, which effectively cleaves SARS-CoV-2 and influenza virus, with the potential to broadly target 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) 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.
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