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Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza.
Abbott, Timothy R; Dhamdhere, Girija; Liu, Yanxia; Lin, Xueqiu; Goudy, Laine; Zeng, Leiping; Chemparathy, Augustine; Chmura, Stephen; Heaton, Nicholas S; Debs, Robert; Pande, Tara; Endy, Drew; La Russa, Marie F; Lewis, David B; Qi, Lei S.
  • Abbott TR; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Dhamdhere G; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
  • Liu Y; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Lin X; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Goudy L; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Zeng L; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Chemparathy A; Department of Management Science and Engineering, Stanford University, Stanford, CA 94305, USA.
  • Chmura S; DNARx, San Francisco, CA 94107, USA.
  • Heaton NS; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Debs R; DNARx, San Francisco, CA 94107, USA.
  • Pande T; Los Altos High School, Los Altos, CA 94022, USA.
  • Endy D; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • La Russa MF; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. Electronic address: mlarussa@stanford.edu.
  • Lewis DB; Department of Pediatrics, Stanford University, Stanford, CA 94305, USA. Electronic address: dblewis@stanford.edu.
  • Qi LS; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA; ChEM-H, Stanford University, Stanford, CA 94305, USA. Electronic address: stanley.qi@stanford.edu.
Cell ; 181(4): 865-876.e12, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-684968
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / RNA, Viral / Influenza A Virus, H1N1 Subtype / CRISPR-Cas Systems / Betacoronavirus Type of study: Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.04.020

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / RNA, Viral / Influenza A Virus, H1N1 Subtype / CRISPR-Cas Systems / Betacoronavirus Type of study: Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.04.020