Evidence map›Paper›PMID 31607545›Full record

ArticleMolecular cell2019

Programmable Inhibition and Detection of RNA Viruses Using Cas13.

Catherine A Freije, Cameron Myhrvold, Chloe K Boehm, Aaron E Lin, Nicole L Welch, Amber Carter, Hayden C Metsky, Cynthia Y Luo, Omar O Abudayyeh, Jonathan S Gootenberg and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

217 citing papers in PubMed, 1 synthesis or guideline pooled it.

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157 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Catherine A FreijeBroad 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.
Cameron MyhrvoldBroad 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.
Chloe K BoehmBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
Aaron E LinBroad 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.
Nicole L WelchBroad 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.
Amber CarterBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
Hayden C MetskyBroad 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.
Cynthia Y LuoBroad 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.
Omar O AbudayyehBroad 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.
Jonathan S GootenbergBroad 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.
Nathan L YozwiakBroad 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.
Feng ZhangBroad 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.
Pardis C SabetiBroad 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.

Funding

Viral Genomics: evolution, spread, and host interactionsU19AI110818 · NIAID · BROAD INSTITUTE, INC. · PI NEAFSEY, DANIEL E · 2014 to 2024
$66.5M
Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
Programmable RNA-targeting toolsR01HG009761 · NHGRI · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2017 to 2024
$7.5M
Exploration of Diverse Mobile Genetic Elements for Precision Genome ManipulationDP1HL141201 · NHLBI · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2017 to 2021
$6.2M
Massively-parallel functional interrogation of psychiatric geneticsR01MH110049 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2015 to 2019
$5.5M
NHGRI NIH HHS R01 HG009761NHGRI NIH HHS RM1 HG006193NHLBI NIH HHS DP1 HL141201NIAID NIH HHS U19 AI110818NIMH NIH HHS R01 MH110049
6 · The paper itself

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.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsRNA StabilityA549 CellsAnimalsChlorocebus aethiopsCRISPR-Associated ProteinsDogsEscherichia coliGene TargetingHEK293 CellsHumansMadin Darby Canine Kidney CellsRNA, ViralRNA VirusesVero CellsCRISPR-Associated ProteinsRNA, ViralantiviralArenavirusCas13Cas13-based detectionCRISPRcrRNA designinfluenza virusmultiplexingRNA interferenceRNA viruses

Identifiers

PMID31607545
PMCPMC7422627

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.