Evidence map›Paper›PMID 20876694›Full record

ArticleNucleic acids research2011

Single-strand nicks induce homologous recombination with less toxicity than double-strand breaks using an AAV vector template.

Michael J Metzger, Audrey McConnell-Smith, Barry L Stoddard, A Dusty Miller

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

48 citing papers in PubMed, 83 citations in OpenAlex.

  1. The Biology of Nucleus-Forming Jumbo Phages.Annual review of genetics · 2025
    Review
  2. Review
  3. Article
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  6. Review
  7. CRISPR Genome Editing Systems in the GenusJournal of bacteriology · 2019
    Review
  8. Development of a CRISPR/Cas9 System for Methylococcus capsulatusApplied and environmental microbiology · 2019
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Genome editing: a robust technology for human stem cells.Cellular and molecular life sciences : CMLS · 2017
    Review
  17. Article
  18. Article
  19. Review
  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

4 authors at 2 institutions in 2 countries.

Michael J MetzgerHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Audrey McConnell-Smith
Barry L Stoddard
A Dusty Miller
Fred Hutch Cancer Center · USUniversity of Washington · US

Funding

PILOT STUDY--RETROVIRUS MEDIATED TRANSFER OF HUMAN GLUCOCEREBROSIDASE GENEP30DK047754 · NIDDK · UNIVERSITY OF WASHINGTON · PI MILLER, ARTHUR DUSTY · 1994 to 2008
$8.4M
Structure, function &engineering of nuclease catalystsR01GM049857 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STODDARD, BARRY L. · 1994 to 2014
$4.2M
Northwest Genome Engineering Consortium (Component 1 of 11)UL1DE019582 · NIDCR · SEATTLE CHILDREN'S HOSPITAL · PI SCHARENBERG, ANDREW M. · 2008 to 2011
$3.1M
VIRAL ONCOLOGYT32CA009229 · NCI · UNIVERSITY OF WASHINGTON · PI LINIAL, MAXINE L · 1985 to 2007
$3.0M
NCI NIH HHS CA09229NIDCR NIH HHS UL1 DE019582NIDCR NIH HHS UL1 DE19582NIDDK NIH HHS P30 DK47754NIGMS NIH HHS R01 GM049857
6 · The paper itself

Abstract

Gene targeting by homologous recombination (HR) can be induced by double-strand breaks (DSBs), however these breaks can be toxic and potentially mutagenic. We investigated the I-AniI homing endonuclease engineered to produce only nicks, and found that nicks induce HR with both plasmid and adeno-associated virus (AAV) vector templates. The rates of nick-induced HR were lower than with DSBs (24-fold lower for plasmid transfection and 4- to 6-fold lower for AAV vector infection), but they still represented a significant increase over background (240- and 30-fold, respectively). We observed severe toxicity with the I-AniI 'cleavase', but no evidence of toxicity with the I-AniI 'nickase.' Additionally, the frequency of nickase-induced mutations at the I-AniI site was at least 150-fold lower than that induced by the cleavase. These results, and the observation that the surrounding sequence context of a target site affects nick-induced HR but not DSB-induced HR, strongly argue that nicks induce HR through a different mechanism than DSBs, allowing for gene correction without the toxicity and mutagenic activity of DSBs.

Indexed as

DNA Breaks, Double-StrandedRecombination, GeneticCell LineDependovirusEndodeoxyribonucleasesGenetic VectorsHumansMutationTemplates, GeneticEndodeoxyribonucleases

Identifiers

PMID20876694
PMCPMC3035452
OpenAlexW2100818027

What OpenQuestion holds

Textmetadata
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.