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 G Ekert, Rajeev Rudraraju, Sharon R Lewin, Joseph A Trapani

Cold Spring Harbor Laboratory

Abstract

ABSTRACTMutation-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-co..

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