Evidence map›Paper›PMID 21912657›Full record

ArticlePloS one2011

DNA nicks promote efficient and safe targeted gene correction.

Luther Davis, Nancy Maizels

Abstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Genome editing: a robust technology for human stem cells.Cellular and molecular life sciences : CMLS · 2017
    Review
  10. Control of gene editing by manipulation of DNA repair mechanisms.Mammalian genome : official journal of the International Mammalian Genome Society · 2017
    Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Salient Features of Endonuclease Platforms for Therapeutic Genome Editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  16. Designed nucleases for targeted genome editing.Plant biotechnology journal · 2016
    Review
  17. Review
  18. Article
  19. Article
  20. Article
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

2 authors.

Luther DavisDepartment of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Nancy Maizels

Funding

MECHANISMS OF SOMATIC MUTATION OF IMMUNOGLOBULIN GENESR01GM041712 · NIGMS · YALE UNIVERSITY · PI MAIZELS, NANCY · 1990 to 2011
$3.4M
Targeted Gene Repair by Homologous Recombination (Component 8 of 11)RL1GM084434 · NIGMS · UNIVERSITY OF WASHINGTON · PI MAIZELS, NANCY · 2007 to 2011
$2.0M
NIGMS NIH HHS R01 GM041712NIGMS NIH HHS R01 GM41712NIGMS NIH HHS RL1 GM084434NIGMS NIH HHS RL1 GM84344
6 · The paper itself

Abstract

Targeted gene correction employs a site-specific DNA lesion to promote homologous recombination that eliminates mutation in a disease gene of interest. The double-strand break typically used to initiate correction can also result in genomic instability if deleterious repair occurs rather than gene correction, possibly compromising the safety of targeted gene correction. Here we show that single-strand breaks (nicks) and double-strand breaks both promote efficient gene correction. However, breaks promote high levels of inadvertent but heritable genomic alterations both locally and elsewhere in the genome, while nicks are accompanied by essentially no collateral local mutagenesis, and thus provide a safer approach to gene correction. Defining efficacy as the ratio of gene correction to local deletion, nicks initiate gene correction with 70-fold greater efficacy than do double-strand breaks (29.0±6.0% and 0.42±0.03%, respectively). Thus nicks initiate efficient gene correction, with limited local mutagenesis. These results have clear therapeutic implications, and should inform future design of meganucleases for targeted gene correction.

Indexed as

DNA Breaks, Single-StrandedDNA Breaks, Double-StrandedDNA End-Joining RepairEndodeoxyribonucleasesHEK293 CellsHumansTargeted Gene RepairEndodeoxyribonucleases

Identifiers

PMID21912657
PMCPMC3164693

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.