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Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza
Author(s) -
Timothy R. Abbott,
Girija Dhamdhere,
Yanxia Liu,
Xueqiu Lin,
Laine Goudy,
Leiping Zeng,
Augustine Chemparathy,
Steven A. Chmura,
Nicholas S. Heaton,
Robert J. Debs,
Tara Pande,
Drew Endy,
Marie La Russa,
David B. Lewis,
Lei S. Qi
Publication year - 2020
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2020.04.020
Subject(s) - crispr , biology , virology , virus , coronavirus , pandemic , influenza a virus , covid-19 , computational biology , disease , infectious disease (medical specialty) , genetics , gene , medicine , pathology
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.

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