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Treatment of influenza and SARS-CoV-2 infections via mRNA-encoded Cas13a in rodents.
Blanchard, Emmeline L; Vanover, Daryll; Bawage, Swapnil Subhash; Tiwari, Pooja Munnilal; Rotolo, Laura; Beyersdorf, Jared; Peck, Hannah E; Bruno, Nicholas C; Hincapie, Robert; Michel, Frank; Murray, Jackelyn; Sadhwani, Heena; Vanderheyden, Bob; Finn, M G; Brinton, Margo A; Lafontaine, Eric R; Hogan, Robert J; Zurla, Chiara; Santangelo, Philip J.
  • Blanchard EL; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • Vanover D; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • Bawage SS; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • Tiwari PM; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • Rotolo L; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • Beyersdorf J; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • Peck HE; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
  • Bruno NC; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
  • Hincapie R; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
  • Michel F; Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine University of Georgia, Athens, GA, USA.
  • Murray J; Department of Infectious Diseases, College of Veterinary Medicine University of Georgia, Athens, GA, USA.
  • Sadhwani H; Department of Biology, Georgia State University, Atlanta, GA, USA.
  • Vanderheyden B; Analytics and Data Science Institute, Kennesaw State University, Kennesaw, GA, USA.
  • Finn MG; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
  • Brinton MA; Department of Biology, Georgia State University, Atlanta, GA, USA.
  • Lafontaine ER; Department of Infectious Diseases, College of Veterinary Medicine University of Georgia, Athens, GA, USA.
  • Hogan RJ; Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine University of Georgia, Athens, GA, USA.
  • Zurla C; Department of Infectious Diseases, College of Veterinary Medicine University of Georgia, Athens, GA, USA.
  • Santangelo PJ; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. chiara@gatech.edu.
Nat Biotechnol ; 39(6): 717-726, 2021 06.
Article in English | MEDLINE | ID: covidwho-1065901
ABSTRACT
Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Messenger / Influenza, Human / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Nat Biotechnol Journal subject: Biotechnology Year: 2021 Document Type: Article Affiliation country: S41587-021-00822-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Messenger / Influenza, Human / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Nat Biotechnol Journal subject: Biotechnology Year: 2021 Document Type: Article Affiliation country: S41587-021-00822-w