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Mol Cell DOI:10.1016/j.molcel.2019.09.013

Programmable Inhibition and Detection of RNA Viruses Using Cas13.

Publication TypeJournal Article
Year of Publication2019
AuthorsFreije, CA, Myhrvold, C, Boehm, CK, Lin, AE, Welch, NL, Carter, A, Metsky, HC, Luo, CY, Abudayyeh, OO, Gootenberg, JS, Yozwiak, NL, Zhang, F, Sabeti, PC
JournalMol Cell
Date Published2019 Oct 02
ISSN1097-4164
Abstract

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.

DOI10.1016/j.molcel.2019.09.013
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31607545?dopt=Abstract

Alternate JournalMol. Cell
PubMed ID31607545