Programmable Inhibition and Detection of RNA Viruses Using Cas13
Name
1-s2.0-S1097276519306987-main.pdf
Description
Published version
Size
2.95 MB
Format
Adobe PDF
Checksum (MD5)
7093c4be4d026b45eedd125478729332
Author(s)
Freije, Catherine A
Myhrvold, Cameron
Boehm, Chloe K
Lin, Aaron E
Welch, Nicole L
Carter, Amber
Metsky, Hayden C
Luo, Cynthia Y
Abudayyeh, Omar O
Gootenberg, Jonathan S
Date Issued
2019
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Freije, Catherine A, Myhrvold, Cameron, Boehm, Chloe K, Lin, Aaron E, Welch, Nicole L et al. 2019. "Programmable Inhibition and Detection of RNA Viruses Using Cas13." Molecular Cell, 76 (5).
Version
Final published version
Abstract
© 2019 The Authors The CRISPR effector Cas13 could be an effective antiviral for single-stranded RNA (ssRNA) viruses because it programmably cleaves RNAs complementary to its CRISPR RNA (crRNA). Here, we computationally identify thousands of potential Cas13 crRNA target sites in hundreds of ssRNA viral species that can potentially infect humans. We experimentally demonstrate Cas13's potent activity against three distinct ssRNA viruses: lymphocytic choriomeningitis virus (LCMV); influenza A virus (IAV); and vesicular stomatitis virus (VSV). Combining this antiviral activity with Cas13-based diagnostics, we develop Cas13-assisted restriction of viral expression and readout (CARVER), an end-to-end platform that uses Cas13 to detect and destroy viral RNA. We further screen hundreds of crRNAs along the LCMV genome to evaluate how conservation and target RNA nucleotide content influence Cas13's antiviral activity. Our results demonstrate that Cas13 can be harnessed to target a wide range of ssRNA viruses and CARVER's potential broad utility for rapid diagnostic and antiviral drug development. Freije et al. demonstrate that Cas13 can be programmed to target and destroy the genomes of diverse mammalian single-stranded RNA viruses. They identify design principles for efficient Cas13 targeting of viral RNA and create companion Cas13-based diagnostics to rapidly measure the effects of Cas13 targeting.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2019.09.013
