Evidence map›Paper›PMID 27325776›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Versatile in vivo regulation of tumor phenotypes by dCas9-mediated transcriptional perturbation.

Christian J Braun, Peter M Bruno, Max A Horlbeck, Luke A Gilbert, Jonathan S Weissman, Michael T Hemann

Abstract readEvaluation Study
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing 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

55 citing papers in PubMed.

  1. Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  12. AnCancer discovery · 2022
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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

6 authors.

Christian J BraunThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
Peter M BrunoThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
Max A HorlbeckDepartment of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94158; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158; Center for RNA Systems Biology, University of California, San Francisco, CA 94158.
Luke A GilbertDepartment of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94158; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158; Center for RNA Systems Biology, University of California, San Francisco, CA 94158.
Jonathan S WeissmanDepartment of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 94158; Howard Hughes Medical Institute, University of California, San Francisco, CA 94158; Center for RNA Systems Biology, University of California, San Francisco, CA 94158.
Michael T HemannThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; hemann@mit.edu.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Tumor Cell Networks CenterU54CA112967 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LAUFFENBURGER, DOUGLAS A · 2004 to 2015
$26.2M
Integrative Program in Complex Biological System (ipCBS)T32EB009383 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSHALL, WALLACE, WEINER, ORION D · 2009 to 2022
$3.2M
NCI NIH HHS P30 CA014051NCI NIH HHS U54 CA112967NIBIB NIH HHS T32 EB009383NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

Targeted transcriptional regulation is a powerful tool to study genetic mediators of cellular behavior. Here, we show that catalytically dead Cas9 (dCas9) targeted to genomic regions upstream or downstream of the transcription start site allows for specific and sustainable gene-expression level alterations in tumor cells in vitro and in syngeneic immune-competent mouse models. We used this approach for a high-coverage pooled gene-activation screen in vivo and discovered previously unidentified modulators of tumor growth and therapeutic response. Moreover, by using dCas9 linked to an activation domain, we can either enhance or suppress target gene expression simply by changing the genetic location of dCas9 binding relative to the transcription start site. We demonstrate that these directed changes in gene-transcription levels occur with minimal off-target effects. Our findings highlight the use of dCas9-mediated transcriptional regulation as a versatile tool to reproducibly interrogate tumor phenotypes in vivo.

Indexed as

Gene Expression Regulation, LeukemicGenetic TechniquesLeukemia, ExperimentalAnimalsBacterial ProteinsCRISPR-Associated Protein 9DacarbazineDNA DamageDNA Modification MethylasesDNA Repair EnzymesDrug Resistance, NeoplasmEndonucleasesMiceSequence Analysis, RNATemozolomideTumor Suppressor Protein p53Bacterial ProteinsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9DacarbazineDNA Modification MethylasesDNA Repair EnzymesEndonucleasesMGMT protein, mouseTemozolomideTumor Suppressor Protein p53Tumor Suppressor Proteinscancer geneticscancer modelscancer therapeutic resistanceCRISPRgene regulation

Identifiers

PMID27325776
PMCPMC4941480

What OpenQuestion holds

Textmetadata
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.