PMID- 31607545
OWN - NLM
STAT- MEDLINE
DCOM- 20200219
LR  - 20200814
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 76
IP  - 5
DP  - 2019 Dec 5
TI  - Programmable Inhibition and Detection of RNA Viruses Using Cas13.
PG  - 826-837.e11
LID - S1097-2765(19)30698-7 [pii]
LID - 10.1016/j.molcel.2019.09.013 [doi]
AB  - 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.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Freije, Catherine A
AU  - Freije CA
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; PhD Program in Virology, Division of Medical Sciences, 
      Harvard Medical School, Boston, MA 02115, USA. Electronic address: 
      cfreije@broadinstitute.org.
FAU - Myhrvold, Cameron
AU  - Myhrvold C
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, 
      Harvard University, Cambridge, MA 02138, USA. Electronic address: 
      cmyhrvol@broadinstitute.org.
FAU - Boehm, Chloe K
AU  - Boehm CK
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA.
FAU - Lin, Aaron E
AU  - Lin AE
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; PhD Program in Virology, Division of Medical Sciences, 
      Harvard Medical School, Boston, MA 02115, USA.
FAU - Welch, Nicole L
AU  - Welch NL
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; PhD Program in Virology, Division of Medical Sciences, 
      Harvard Medical School, Boston, MA 02115, USA.
FAU - Carter, Amber
AU  - Carter A
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA.
FAU - Metsky, Hayden C
AU  - Metsky HC
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; Department of Electrical Engineering and Computer 
      Science, MIT, Cambridge, MA 02142, USA.
FAU - Luo, Cynthia Y
AU  - Luo CY
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, 
      Harvard University, Cambridge, MA 02138, USA.
FAU - Abudayyeh, Omar O
AU  - Abudayyeh OO
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; McGovern Institute for Brain Research, MIT, Cambridge, 
      MA 02139, USA; Department of Brain and Cognitive Science, MIT, Cambridge, MA 
      02139, USA; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA; 
      Department of Health Sciences and Technology, MIT, Cambridge, MA 02139, USA.
FAU - Gootenberg, Jonathan S
AU  - Gootenberg JS
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; McGovern Institute for Brain Research, MIT, Cambridge, 
      MA 02139, USA; Department of Brain and Cognitive Science, MIT, Cambridge, MA 
      02139, USA; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA; 
      Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
FAU - Yozwiak, Nathan L
AU  - Yozwiak NL
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; Department of Organismic and Evolutionary Biology, 
      Harvard University, Cambridge, MA 02138, USA.
FAU - Zhang, Feng
AU  - Zhang F
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; McGovern Institute for Brain Research, MIT, Cambridge, 
      MA 02139, USA; Department of Brain and Cognitive Science, MIT, Cambridge, MA 
      02139, USA; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA; 
      Howard Hughes Medical Institute (HHMI), Chevy Chase, MD 20815, USA.
FAU - Sabeti, Pardis C
AU  - Sabeti PC
AD  - Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 
      Cambridge, MA 02142, USA; PhD Program in Virology, Division of Medical Sciences, 
      Harvard Medical School, Boston, MA 02115, USA; Department of Organismic and 
      Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes 
      Medical Institute (HHMI), Chevy Chase, MD 20815, USA; Department of Immunology 
      and Infectious Disease, T.H. Chan Harvard School of Public Health, Boston, MA 
      02115, USA. Electronic address: pardis@broadinstitute.org.
LA  - eng
GR  - R01 MH110049/MH/NIMH NIH HHS/United States
GR  - DP1 HL141201/HL/NHLBI NIH HHS/United States
GR  - R01 HG009761/HG/NHGRI NIH HHS/United States
GR  - U19 AI110818/AI/NIAID NIH HHS/United States
GR  - RM1 HG006193/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191010
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (CRISPR-Associated Proteins)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - CRISPR-Associated Proteins/genetics/*metabolism
MH  - *CRISPR-Cas Systems
MH  - Chlorocebus aethiops
MH  - *Clustered Regularly Interspaced Short Palindromic Repeats
MH  - Dogs
MH  - Escherichia coli/enzymology/genetics
MH  - Gene Targeting/*methods
MH  - HEK293 Cells
MH  - Humans
MH  - Madin Darby Canine Kidney Cells
MH  - *RNA Stability
MH  - RNA Viruses/*enzymology/genetics
MH  - RNA, Viral/genetics/*metabolism
MH  - Vero Cells
PMC - PMC7422627
MID - NIHMS1591539
OTO - NOTNLM
OT  - Arenavirus
OT  - CRISPR
OT  - Cas13
OT  - Cas13-based detection
OT  - RNA interference
OT  - RNA viruses
OT  - antiviral
OT  - crRNA design
OT  - influenza virus
OT  - multiplexing
EDAT- 2019/10/15 06:00
MHDA- 2020/02/20 06:00
PMCR- 2020/08/12
CRDT- 2019/10/15 06:00
PHST- 2019/04/16 00:00 [received]
PHST- 2019/07/18 00:00 [revised]
PHST- 2019/09/06 00:00 [accepted]
PHST- 2019/10/15 06:00 [pubmed]
PHST- 2020/02/20 06:00 [medline]
PHST- 2019/10/15 06:00 [entrez]
PHST- 2020/08/12 00:00 [pmc-release]
AID - S1097-2765(19)30698-7 [pii]
AID - 10.1016/j.molcel.2019.09.013 [doi]
PST - ppublish
SO  - Mol Cell. 2019 Dec 5;76(5):826-837.e11. doi: 10.1016/j.molcel.2019.09.013. Epub 
      2019 Oct 10.