Cell
Volume 181, Issue 4, 14 May 2020, Pages 865-876.e12
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Article
Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza

https://doi.org/10.1016/j.cell.2020.04.020Get rights and content
open access

Highlights

  • PAC-MAN is a CRISPR-based strategy for RNA-guided viral RNA inhibition and degradation

  • Cas13d PAC-MAC is effective at targeting and cleaving SARS-CoV-2 sequences

  • Cas13d PAC-MAC can reduce H1N1 IAV load in respiratory epithelial cells

  • A group of six crRNAs can target more than 90% of all coronaviruses

Summary

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.

Keywords

CRISPR
Cas13
COVID-19
SARS-CoV-2
2019-nCoV
RdRP
nucleocapsid
IAV
influenza
antiviral

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These authors contributed equally

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