Evidence map›Paper›PMID 26788852›Full record

ArticlePloS one2016

Exploiting the CRISPR/Cas9 PAM Constraint for Single-Nucleotide Resolution Interventions.

Yi Li, Saurabh Mendiratta, Kristina Ehrhardt, Neha Kashyap, Michael A White, Leonidas Bleris

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Unveiling the invisible genomic dynamics.Experimental & molecular medicine · 2025
    Review
  4. Review
  5. Article
  6. CRISPRingCancers · 2024
    Review
  7. Article
  8. Article
  9. Single-Base Resolution: Increasing the Specificity of the CRISPR-Cas System in Gene Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. The applications of CRISPR/Cas system in molecular detection.Journal of cellular and molecular medicine · 2018
    Review
  16. Article
  17. Article
  18. CRISPR/Cas9 Editing of the Mutant Huntingtin Allele In Vitro and In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Article
  19. Review
  20. Review
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 at 2 institutions in 1 country.

Yi LiBioengineering Department, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, United States of America.
Saurabh MendirattaDepartment of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, United States of America.
Kristina EhrhardtBioengineering Department, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, United States of America.
Neha KashyapBioengineering Department, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, United States of America.
Michael A WhiteDepartment of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, United States of America.
Leonidas BlerisBioengineering Department, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, United States of America.
The University of Texas at Dallas · USThe University of Texas Southwestern Medical Center · US

Funding

Targeting Mechanistic Subtypes of Neoplastic DiseaseR35CA197717 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI WHITE, MICHAEL A. · 2015 to 2015
$725k
Rewiring the miRNA-MDM2-p53 network to reactivate p53 functionR21CA170018 · NCI · UNIVERSITY OF TEXAS DALLAS · PI BLERIS, LEONIDAS, MA, LAN · 2012 to 2013
$354k
Probing the characteristics of genetic circuits integrated in mammalian cells andR15GM096271 · NIGMS · UNIVERSITY OF TEXAS DALLAS · PI BLERIS, LEONIDAS · 2011 to 2011
$306k
NCI NIH HHS CA170018NCI NIH HHS R21 CA170018NCI NIH HHS R35 CA197717NIGMS NIH HHS GM096271NIGMS NIH HHS R15 GM096271
6 · The paper itself

Abstract

CRISPR/Cas9 is an enabling RNA-guided technology for genome targeting and engineering. An acute DNA binding constraint of the Cas9 protein is the Protospacer Adjacent Motif (PAM). Here we demonstrate that the PAM requirement can be exploited to specifically target single-nucleotide heterozygous mutations while exerting no aberrant effects on the wild-type alleles. Specifically, we target the heterozygous G13A activating mutation of KRAS in colorectal cancer cells and we show reversal of drug resistance to a MEK small-molecule inhibitor. Our study introduces a new paradigm in genome editing and therapeutic targeting via the use of gRNA to guide Cas9 to a desired protospacer adjacent motif.

Indexed as

CRISPR-Cas SystemsPolymorphism, Single NucleotideBenzimidazolesCell Line, TumorDrug Resistance, NeoplasmHEK293 CellsHumansProto-Oncogene Proteins p21(ras)RNARNA EditingRNA, Guide, CRISPR-Cas SystemsAZD 6244BenzimidazolesKRAS protein, humanProto-Oncogene Proteins p21(ras)RNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID26788852
PMCPMC4720446
OpenAlexW2329668648

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.