Evidence map›Paper›PMID 26480473›Full record

ArticleNature methods2015

DNA-binding-domain fusions enhance the targeting range and precision of Cas9.

Mehmet Fatih Bolukbasi, Ankit Gupta, Sarah Oikemus, Alan G Derr, Manuel Garber, Michael H Brodsky, Lihua Julie Zhu, Scot A Wolfe

Abstract read
In one paragraph

Article in Nature methods, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing 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

69 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Engineered transcription-associated Cas9 targeting in eukaryotic cells.bioRxiv : the preprint server for biology · 2024
    Article
  6. Article
  7. CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023
    Review
  8. Review
  9. Article
  10. Engineering of efficiency-enhanced Cas9 and base editors with improved gene therapy efficacies.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Eliminating predictable DNA off-target effects of cytosine base editor by using dual guiders including sgRNA and TALE.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  16. Article
  17. Article
  18. Discovery in CRISPR-Cas9 system.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021
    Article
  19. Advanced Nanotheranostics of CRISPR/Cas for Viral Hepatitis and Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
  20. Review

9 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

8 authors.

Mehmet Fatih BolukbasiDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Ankit GuptaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Sarah OikemusDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Alan G DerrProgram in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Manuel GarberProgram in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Michael H BrodskyDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Lihua Julie ZhuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

Funding

University of Massachusetts Center for Clinical Science and Translational SupplementUL1TR001453 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUZURIAGA, KATHERINE F · 2015 to 2024
$39.0M
University of Massachusetts Center for Clinical and Translational ScienceUL1TR000161 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUZURIAGA, KATHERINE F · 2012 to 2015
$11.0M
Rules of gene expression modeled on human dendritic cell response to pathogensU01HG007910 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GARBER, MANUEL, LUBAN, JEREMY · 2015 to 2017
$6.1M
Next generation hybrid nucleases for precise excision of latent HIV-1 provirusR01AI117839 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUBAN, JEREMY, WOLFE, SCOT A · 2015 to 2019
$4.6M
Using zinc finger nucleases to manipulate the zebrafish genomeR01HL093766 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LAWSON, NATHAN D, WOLFE, SCOT A · 2008 to 2017
$4.1M
NCATS NIH HHS UL1 TR000161NCATS NIH HHS UL1 TR001453NHGRI NIH HHS U01 HG007910NHGRI NIH HHS U01HG007910NHLBI NIH HHS R01 HL093766NHLBI NIH HHS R01HL093766NIAID NIH HHS R01 AI117839NIAID NIH HHS R01AI117839
6 · The paper itself

Abstract

The CRISPR-Cas9 system is commonly used in biomedical research; however, the precision of Cas9 is suboptimal for applications that involve editing a large population of cells (for example, gene therapy). Variations on the standard Cas9 system have yielded improvements in the precision of targeted DNA cleavage, but they often restrict the range of targetable sequences. It remains unclear whether these variants can limit lesions to a single site in the human genome over a large cohort of treated cells. Here we show that by fusing a programmable DNA-binding domain (pDBD) to Cas9 and attenuating Cas9's inherent DNA-binding affinity, we were able to produce a Cas9-pDBD chimera with dramatically improved precision and an increased targeting range. Because the specificity and affinity of this framework can be easily tuned, Cas9-pDBDs provide a flexible system that can be tailored to achieve extremely precise genome editing at nearly any genomic locus.

Indexed as

Gene TargetingClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCRISPR-Cas SystemsDNA-Binding ProteinsDNA CleavageHEK293 CellsHumansRNA, Guide, CRISPR-Cas SystemsTranscriptional ActivationTransfectionZinc FingersCRISPR-Associated ProteinsDNA-Binding ProteinsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID26480473
PMCPMC4679368

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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.