Evidence map›Paper›PMID 22373919›Full record

ArticleNucleic acids research2012

Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects.

Cherie L Ramirez, Michael T Certo, Claudio Mussolino, Mathew J Goodwin, Thomas J Cradick, Anton P McCaffrey, Toni Cathomen, Andrew M Scharenberg, J Keith Joung

Abstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing 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

88 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Points of View on the Tools for Genome/Gene Editing.International journal of molecular sciences · 2021
    Review
  10. Genome engineering and disease modelingWorld journal of stem cells · 2021
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Cherie L RamirezMolecular Pathology Unit, Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Michael T Certo
Claudio Mussolino
Mathew J Goodwin
Thomas J Cradick
Anton P McCaffrey
Toni Cathomen
Andrew M Scharenberg
J Keith Joung

Funding

TRAINING IN MOLECULAR AND CELLULAR BIOLOGYT32GM007270 · NIGMS · UNIVERSITY OF WASHINGTON · PI RAIBLE, DAVID W · 1985 to 2020
$21.0M
Causal Transcriptional Consequences of Human Genetic VariationP50HG005550 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2010 to 2014
$19.0M
ADVANCING ZINC FINGER NUCLEASES FOR TARGETED GENOME MANIPULATIONR01GM088040 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH, PETERSON, RANDALL T · 2009 to 2016
$4.5M
Northwest Genome Engineering Consortium (Component 1 of 11)UL1DE019582 · NIDCR · SEATTLE CHILDREN'S HOSPITAL · PI SCHARENBERG, ANDREW M. · 2008 to 2011
$3.1M
Advancing stem cell technologies using engineered zinc finger proteinsDP1GM105378 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2012 to 2014
$2.6M
Directed Protein Evolution for Design of LAGLIDADGs with Novel Recognition SpeciRL1CA133832 · NCI · SEATTLE CHILDREN'S HOSPITAL · PI SCHARENBERG, ANDREW M. · 2007 to 2011
$2.2M
Advancing stem cell technologies using engineered zinc finger proteinsDP1OD006862 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI JOUNG, J. KEITH · 2010 to 2011
$1.8M
Novel Therapeutic Approaches for Eliminating Hepatitis B Virus DNAs and RNAsR01AI068885 · NIAID · UNIVERSITY OF IOWA · PI MCCAFFREY, ANTON P · 2007 to 2010
$1.5M
NCI NIH HHS RL1 CA133832NHGRI NIH HHS P50 HG005550NIAID NIH HHS R01 AI068885NIDCR NIH HHS UL1 DE019582NIGMS NIH HHS DP1 GM105378NIGMS NIH HHS R01 GM088040NIGMS NIH HHS T32 GM07270NIH HHS DP1 OD006862
6 · The paper itself

Abstract

Engineered zinc finger nucleases (ZFNs) induce DNA double-strand breaks at specific recognition sequences and can promote efficient introduction of desired insertions, deletions or substitutions at or near the cut site via homology-directed repair (HDR) with a double- and/or single-stranded donor DNA template. However, mutagenic events caused by error-prone non-homologous end-joining (NHEJ)-mediated repair are introduced with equal or higher frequency at the nuclease cleavage site. Furthermore, unintended mutations can also result from NHEJ-mediated repair of off-target nuclease cleavage sites. Here, we describe a simple and general method for converting engineered ZFNs into zinc finger nickases (ZFNickases) by inactivating the catalytic activity of one monomer in a ZFN dimer. ZFNickases show robust strand-specific nicking activity in vitro. In addition, we demonstrate that ZFNickases can stimulate HDR at their nicking site in human cells, albeit at a lower frequency than by the ZFNs from which they were derived. Finally, we find that ZFNickases appear to induce greatly reduced levels of mutagenic NHEJ at their target nicking site. ZFNickases thus provide a promising means for inducing HDR-mediated gene modifications while reducing unwanted mutagenesis caused by error-prone NHEJ.

Indexed as

Recombinational DNA RepairCell LineDeoxyribonucleases, Type II Site-SpecificDNA CleavageDNA End-Joining RepairGenes, ReporterGreen Fluorescent ProteinsHEK293 CellsHumansMutagenesisProtein EngineeringZinc FingersDeoxyribonucleases, Type II Site-Specificendodeoxyribonuclease FokIenhanced green fluorescent proteinGreen Fluorescent Proteins

Identifiers

PMID22373919
PMCPMC3384306

What OpenQuestion holds

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LicenceCC BY-NC
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.