Evidence map›Paper›PMID 30451839›Full record

ArticleNature communications2018

Orthogonal Cas9-Cas9 chimeras provide a versatile platform for genome editing.

Mehmet Fatih Bolukbasi, Pengpeng Liu, Kevin Luk, Samantha F Kwok, Ankit Gupta, Nadia Amrani, Erik J Sontheimer, Lihua Julie Zhu, Scot A Wolfe

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Article
  2. Article
  3. CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Can Designer Indels Be Tailored by Gene Editing?: Can Indels Be Customized?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Mehmet Fatih BolukbasiDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Pengpeng LiuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Kevin LukDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Samantha F KwokDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Ankit GuptaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Nadia AmraniRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Erik J SontheimerRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-0881-0310
Lihua Julie ZhuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-7416-0590
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA. scot.wolfe@umassmed.edu.

Funding

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
Engineered Cas9 Nucleases with Single-Genomic-Site Precision for CYBB CorrectionR01GM115911 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SONTHEIMER, ERIK J., WOLFE, SCOT A · 2016 to 2019
$1.6M
NHLBI NIH HHS R01 HL093766NIAID NIH HHS R01 AI117839NIGMS NIH HHS R01 GM115911
6 · The paper itself

Abstract

The development of robust, versatile and accurate toolsets is critical to facilitate therapeutic genome editing applications. Here we establish RNA-programmable Cas9-Cas9 chimeras, in single- and dual-nuclease formats, as versatile genome engineering systems. In both of these formats, Cas9-Cas9 fusions display an expanded targeting repertoire and achieve highly specific genome editing. Dual-nuclease Cas9-Cas9 chimeras have distinct advantages over monomeric Cas9s including higher target site activity and the generation of predictable precise deletion products between their target sites. At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable.

Indexed as

Base SequenceCRISPR-Cas SystemsSequence DeletionBacterial ProteinsCarrier ProteinsEndonucleasesGene EditingGenetic EngineeringGenome, HumanHEK293 CellsHumansJurkat CellsK562 CellsMutant Chimeric ProteinsNeisseria meningitidisNuclear ProteinsBacterial ProteinsBCL11A protein, humanCarrier ProteinsEndonucleasesMutant Chimeric ProteinsNuclear ProteinsRepressor Proteins

Identifiers

PMID30451839
PMCPMC6242970

What OpenQuestion holds

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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.