Journal article

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

Mohamed Fareh, Wei Zhao, Wenxin Hu, Joshua ML Casan, Amit Kumar, Jori Symons, Ilia Voskoboinik, Paul Ekert, Rajeev Rudraraju, Sharon Lewin, Joseph Trapani

Cold Spring Harbor Laboratory | Published : 2020

Abstract

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-c..

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