دورية أكاديمية
أعرض في EDS

Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance.

التفاصيل البيبلوغرافية
العنوان: Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance.
المؤلفون: Fareh M; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia. Mohamed.fareh@petermac.org.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia. Mohamed.fareh@petermac.org., Zhao W; The Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Hu W; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia., Casan JML; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia., Kumar A; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia., Symons J; The Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Zerbato JM; The Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Fong D; The Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Voskoboinik I; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia., Ekert PG; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.; Murdoch Children's Research Institute, Parkville, Australia.; Children's Cancer Institute, Randwick, NSW, Australia., Rudraraju R; The Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; WHO Collaborating Centre for Research and Reference in Influenza, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Purcell DFJ; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia., Lewin SR; The Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. sharon.lewin@unimelb.edu.au.; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. sharon.lewin@unimelb.edu.au.; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia. sharon.lewin@unimelb.edu.au., Trapani JA; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
المصدر: Nature communications [Nat Commun] 2021 Jul 13; Vol. 12 (1), pp. 4270. Date of Electronic Publication: 2021 Jul 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Mutation*, SARS-CoV-2/*physiology , Virus Replication/*physiology, Animals ; Antiviral Agents/pharmacology ; COVID-19/virology ; CRISPR-Cas Systems ; Chlorocebus aethiops ; Clustered Regularly Interspaced Short Palindromic Repeats ; Drug Development ; Genome, Viral ; HEK293 Cells ; Humans ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism ; Vero Cells ; Virus Replication/genetics ; COVID-19 Drug Treatment
مستخلص: The recent dramatic appearance of variants of concern of SARS-coronavirus-2 (SARS-CoV-2) highlights the need for innovative approaches that simultaneously suppress viral replication and circumvent viral escape from host immunity and antiviral therapeutics. Here, we employ genome-wide computational prediction and single-nucleotide resolution screening to reprogram CRISPR-Cas13b against SARS-CoV-2 genomic and subgenomic RNAs. Reprogrammed Cas13b effectors targeting accessible regions of Spike and Nucleocapsid transcripts achieved >98% silencing efficiency in virus-free models. Further, optimized and multiplexed Cas13b CRISPR RNAs (crRNAs) suppress viral replication in mammalian cells infected with replication-competent SARS-CoV-2, including the recently emerging dominant variant of concern B.1.1.7. The comprehensive mutagenesis of guide-target interaction demonstrated that single-nucleotide mismatches does not impair the capacity of a potent single crRNA to simultaneously suppress ancestral and mutated SARS-CoV-2 strains in infected mammalian cells, including the Spike D614G mutant. The specificity, efficiency and rapid deployment properties of reprogrammed Cas13b described here provide a molecular blueprint for antiviral drug development to suppress and prevent a wide range of SARS-CoV-2 mutants, and is readily adaptable to other emerging pathogenic viruses.
(© 2021. The Author(s).)
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المشرفين على المادة: 0 (Antiviral Agents)
0 (Spike Glycoprotein, Coronavirus)
تواريخ الأحداث: Date Created: 20210714 Date Completed: 20210720 Latest Revision: 20231107
رمز التحديث: 20231107
مُعرف محوري في PubMed: PMC8277810
DOI: 10.1038/s41467-021-24577-9
PMID: 34257311
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-24577-9