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Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza

View ORCID ProfileTimothy R. Abbott, Girija Dhamdhere, Yanxia Liu, Xueqiu Lin, Laine Goudy, Leiping Zeng, Augustine Chemparathy, Stephen Chmura, Nicholas S. Heaton, Robert Debs, Tara Pande, Drew Endy, Marie La Russa, David B. Lewis, View ORCID ProfileLei S. Qi
doi: https://doi.org/10.1101/2020.03.13.991307
Timothy R. Abbott
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Girija Dhamdhere
2Department of Pediatrics, Stanford University, Stanford, CA 94305, USA
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Yanxia Liu
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Xueqiu Lin
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Laine Goudy
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Leiping Zeng
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Augustine Chemparathy
3Department of Management Science & Engineering, Stanford University, Stanford, CA 94305, USA
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Stephen Chmura
4DNARx, San Francisco, CA 94107, USA
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Nicholas S. Heaton
5Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA
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Robert Debs
4DNARx, San Francisco, CA 94107, USA
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Tara Pande
6Los Altos High School, Los Altos, CA 94022, USA
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Drew Endy
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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Marie La Russa
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: mlarussa@stanford.edu dblewis@stanford.edu stanley.qi@stanford.edu
David B. Lewis
2Department of Pediatrics, Stanford University, Stanford, CA 94305, USA
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  • For correspondence: mlarussa@stanford.edu dblewis@stanford.edu stanley.qi@stanford.edu
Lei S. Qi
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
7Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA
8ChEM-H, Stanford University, Stanford, CA 94305, USA
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  • ORCID record for Lei S. Qi
  • For correspondence: mlarussa@stanford.edu dblewis@stanford.edu stanley.qi@stanford.edu
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ABSTRACT

The outbreak of the coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has infected more than 100,000 people worldwide with over 3,000 deaths since December 2019. There is no cure for COVID-19 and the vaccine development is estimated to require 12-18 months. Here we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (Prophylactic Antiviral CRISPR in huMAN cells), for viral inhibition that can effectively degrade SARS-CoV-2 sequences and live influenza A virus (IAV) genome in human lung epithelial cells. We designed and screened a group of CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs for cleaving SARS-CoV-2. The approach is effective in reducing respiratory cell viral replication for H1N1 IAV. Our bioinformatic analysis showed a group of only six crRNAs can target more than 90% of all coronaviruses. The PAC-MAN approach is potentially a rapidly implementable pan-coronavirus strategy to deal with emerging pandemic strains.

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Posted March 14, 2020.
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Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza
Timothy R. Abbott, Girija Dhamdhere, Yanxia Liu, Xueqiu Lin, Laine Goudy, Leiping Zeng, Augustine Chemparathy, Stephen Chmura, Nicholas S. Heaton, Robert Debs, Tara Pande, Drew Endy, Marie La Russa, David B. Lewis, Lei S. Qi
bioRxiv 2020.03.13.991307; doi: https://doi.org/10.1101/2020.03.13.991307
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Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza
Timothy R. Abbott, Girija Dhamdhere, Yanxia Liu, Xueqiu Lin, Laine Goudy, Leiping Zeng, Augustine Chemparathy, Stephen Chmura, Nicholas S. Heaton, Robert Debs, Tara Pande, Drew Endy, Marie La Russa, David B. Lewis, Lei S. Qi
bioRxiv 2020.03.13.991307; doi: https://doi.org/10.1101/2020.03.13.991307

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