Evidence map›Paper›PMID 26035283›Full record

ArticleScientific reports2015

CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus.

Vyas Ramanan, Amir Shlomai, David B T Cox, Robert E Schwartz, Eleftherios Michailidis, Ankit Bhatta, David A Scott, Feng Zhang, Charles M Rice, Sangeeta N Bhatia

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed
–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

155 citing papers in PubMed.

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95 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

10 authors.

Vyas RamananDepartment of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Amir ShlomaiLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
David B T Cox1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Broad Institute, Cambridge, MA 02139, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Robert E Schwartz1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA [3] Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
Eleftherios MichailidisLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
Ankit BhattaLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
David A Scott1] Broad Institute, Cambridge, MA 02139, USA [2] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Feng Zhang1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Broad Institute, Cambridge, MA 02139, USA [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 [4] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Charles M RiceLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
Sangeeta N Bhatia1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA [3] Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [4] Broad Institute, Cambridge, MA 02139, USA [5] Howard Hughes Medical Institute, Cambridge, MA 02139, USA [6] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6M
Modeling human hepatotropic infections in complex tissue organoidsR01DK085713 · NIDDK · ROCKEFELLER UNIVERSITY · PI BHATIA, SANGEETA N., RICE, CHARLES M · 2009 to 2013
$5.6M
Massively-parallel functional interrogation of psychiatric geneticsR01MH110049 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2015 to 2019
$5.5M
Probing Neuropsychiatric Diseases Using Targeted Epigenome and Genome EngineeringDP1MH100706 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2012 to 2016
$4.3M
Genome-wide Light-inducible Tuning of Transcriptional Network DynamicR01NS073124 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ARLOTTA, PAOLA, JOUNG, J. KEITH · 2010 to 2014
$3.3M
New Hepatocyte Model Systems to study Hepatitis B Virus InfectionK08DK101754 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI SCHWARTZ, ROBERT E · 2014 to 2018
$781k
Howard Hughes Medical InstituteNCATS NIH HHS 8 UL1 TR000043NCATS NIH HHS UL1 TR000043NCCDPHP CDC HHS 5DP1-MH100706NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NIDDK NIH HHS 1K08DK101754NIDDK NIH HHS DK085713NIDDK NIH HHS K08 DK101754NIDDK NIH HHS R01 DK085713NIEHS NIH HHS P30 ES002109NIEHS NIH HHS P30-ES002109NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32GM007753NIMH NIH HHS DP1 MH100706NIMH NIH HHS R01 MH110049NINDS NIH HHS 5R01-NS073124NINDS NIH HHS R01 NS073124
6 · The paper itself

Abstract

Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients.

Indexed as

CRISPR-Cas SystemsAnimalsCell Line, TumorCells, CulturedClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsDisease Models, AnimalDNA, CircularDNA, ViralGene Expression Regulation, ViralGene TargetingHepatitis BHepatitis B virusHumansMiceRNA, Guide, CRISPR-Cas SystemsCRISPR-Associated ProteinsDNA, CircularDNA, ViralRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID26035283
PMCPMC4649911

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Registered trials

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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.