| Property | Value |
|---|
|
?:abstract
|
-
Mutation-driven evolution of SARS coronavirus-2 (SARS-CoV-2) highlights the need for innovative approaches that simultaneously suppress viral replication and circumvent viral escape routes from host immunity and antiviral therapeutics. Here, we employed genome-wide computational prediction and singlenucleotide 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 gRNAs suppressed viral replication by up to 90% in mammalian cells infected with replication-competent SARS-CoV-2. Unexpectedly, the comprehensive mutagenesis of guide-target interaction demonstrated that single-nucleotide mismatches do not impair the capacity of a potent single gRNA to simultaneously suppress ancestral and mutated SARS-CoV-2 in infected mammalian cells, including the highly infectious and globally disseminated Spike D614G mutant. The specificity, efficiency and rapid deployment properties of reprogrammed Cas13b described here provide a molecular blueprint of antiviral therapeutics to simultaneously suppress a wide range of SARS-CoV-2 mutants, and is readily adaptable to other emerging pathogenic viruses.
|
|
is
?:annotates
of
|
|
|
?:creator
|
|
|
?:doi
|
|
|
?:doi
|
-
10.1101/2020.11.18.389312
|
|
?:externalLink
|
|
|
?:journal
|
|
|
?:license
|
|
|
?:pdf_json_files
|
-
document_parses/pdf_json/d78ffca28c92c30931a1f4b9ba617cb6da286ac4.json
|
|
?:publication_isRelatedTo_Disease
|
|
|
?:sha_id
|
|
|
?:source
|
|
|
?:title
|
-
Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance
|
|
?:type
|
|
|
?:year
|
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}