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Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro.
Zeng, Leiping; Liu, Yanxia; Nguyenla, Xammy Huu; Abbott, Timothy R; Han, Mengting; Zhu, Yanyu; Chemparathy, Augustine; Lin, Xueqiu; Chen, Xinyi; Wang, Haifeng; Rane, Draven A; Spatz, Jordan M; Jain, Saket; Rustagi, Arjun; Pinsky, Benjamin; Zepeda, Adrianna E; Kadina, Anastasia P; Walker, John A; Holden, Kevin; Temperton, Nigel; Cochran, Jennifer R; Barron, Annelise E; Connolly, Michael D; Blish, Catherine A; Lewis, David B; Stanley, Sarah A; La Russa, Marie F; Qi, Lei S.
Afiliação
  • Zeng L; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Liu Y; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Nguyenla XH; Department of Molecular and Cellular Biology, University of California, Berkeley, CA, 94720, USA.
  • Abbott TR; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Han M; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Zhu Y; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Chemparathy A; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Lin X; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Chen X; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Wang H; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Rane DA; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Spatz JM; Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.
  • Jain S; University of California San Francisco, San Francisco, CA, 94143, USA.
  • Rustagi A; Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
  • Pinsky B; Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
  • Zepeda AE; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Kadina AP; Synthego Corporation, Redwood City, CA, USA.
  • Walker JA; Synthego Corporation, Redwood City, CA, USA.
  • Holden K; Synthego Corporation, Redwood City, CA, USA.
  • Temperton N; Synthego Corporation, Redwood City, CA, USA.
  • Cochran JR; Viral Pseudotype Unit, Medway School of Pharmacy, Chatham, Kent ME4 4TB, UK.
  • Barron AE; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Connolly MD; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • Blish CA; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
  • Lewis DB; Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
  • Stanley SA; Chan Zuckerberg BioHub, San Francisco, CA, 94158, USA.
  • La Russa MF; Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.
  • Qi LS; Department of Molecular and Cellular Biology, University of California, Berkeley, CA, 94720, USA. sastanley@berkeley.edu.
Nat Commun ; 13(1): 2766, 2022 05 19.
Article em En | MEDLINE | ID: mdl-35589813
ABSTRACT
A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic effects of diverse small molecule drugs against coronaviruses for prophylaxis or treatment purposes, and the best combination reduced viral titer by over four orders of magnitude. Using lipid nanoparticle-mediated RNA delivery, we demonstrate that the Cas13d system can effectively treat infection from multiple variants of coronavirus, including Omicron SARS-CoV-2, in human primary airway epithelium air-liquid interface (ALI) cultures. Our study establishes CRISPR-Cas13 as a BSA which is highly complementary to existing vaccination and antiviral treatment strategies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / Tratamento Farmacológico da COVID-19 Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: SARS-CoV-2 / Tratamento Farmacológico da COVID-19 Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article