Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro.

Autor: 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.; Department of Pathology, Stanford University, Stanford, CA, USA., Zepeda AE; Synthego Corporation, Redwood City, CA, USA., Kadina AP; Synthego Corporation, Redwood City, CA, USA., Walker JA 3rd; Synthego Corporation, Redwood City, CA, USA., Holden K; Synthego Corporation, Redwood City, CA, USA., Temperton N; Viral Pseudotype Unit, Medway School of Pharmacy, Chatham, Kent ME4 4TB, UK., Cochran JR; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA., Barron AE; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA., Connolly MD; Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA., Blish CA; Department of Medicine, Stanford University, Stanford, CA, 94305, USA.; Chan Zuckerberg BioHub, San Francisco, CA, 94158, USA., Lewis DB; Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA., Stanley SA; Department of Molecular and Cellular Biology, University of California, Berkeley, CA, 94720, USA. sastanley@berkeley.edu., La Russa MF; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA. mlarussa@stanford.edu., Qi LS; Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA. stanley.qi@stanford.edu.; Chan Zuckerberg BioHub, San Francisco, CA, 94158, USA. stanley.qi@stanford.edu.; Sarafan ChEM-H, Stanford University, Stanford, CA, 94305, USA. stanley.qi@stanford.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 May 19; Vol. 13 (1), pp. 2766. Date of Electronic Publication: 2022 May 19.
DOI: 10.1038/s41467-022-30546-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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