Authors: 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 F. La Russa, David B. Lewis, Lei S. Qi
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.
Source: Cell, 2020; 181 (4): 865