Evidence map›Paper›PMID 25282150›Full record

ArticleNature structural & molecular biology2014

A genome-wide map of adeno-associated virus-mediated human gene targeting.

David R Deyle, R Scott Hansen, Anda M Cornea, Li B Li, Amber A Burt, Ian E Alexander, Richard S Sandstrom, John A Stamatoyannopoulos, Chia-Lin Wei, David W Russell

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. AAV-mediated genome editing is influenced by the formation of R-loops.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  2. Article
  3. Review
  4. Evaluating the Genomic Parameters Governing rAAV-Mediated Homologous Recombination.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  5. Review
  6. Article
  7. Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  8. Structural basis for spumavirus GAG tethering to chromatin.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  9. Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  10. 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

10 authors at 3 institutions in 2 countries.

David R DeyleDepartment of Medicine, University of Washington, Seattle, Washington, USA.
R Scott HansenDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Anda M CorneaDepartment of Molecular and Cellular Biology, University of Washington, Seattle, Washington, USA.
Li B LiDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Amber A BurtDepartment of Medicine, University of Washington, Seattle, Washington, USA.
Ian E AlexanderGene Therapy Research Unit, Children's Medical Research Institute, Westmead, New South Wales, Australia.
Richard S SandstromDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.ORCID 0000000233561547
John A StamatoyannopoulosDepartment of Genome Sciences, University of Washington, Seattle, Washington, USA.
Chia-Lin WeiGenomic Technologies Department, Joint Genome Institute, Walnut Creek, California, USA.
David W Russell1] Department of Medicine, University of Washington, Seattle, Washington, USA. [2] Department of Biochemistry, University of Washington, Seattle, Washington, USA.
University of Washington · USChildren's Medical Research Institute · AUJoint Genome Institute · US

Funding

VECTOR CONSTRUCTIONS FOR GENE THERAPY OF SICKLE CELL DISEASEP01HL053750 · NHLBI · UNIVERSITY OF WASHINGTON · PI RIVIERI, ISABELLE · 1994 to 2014
$30.4M
University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
A Comprehensive Catalog of Dnasel Hypersensitive SitesU54HG007010 · NHGRI · UNIVERSITY OF WASHINGTON · PI STAMATOYANNOPOULOS, JOHN A · 2012 to 2016
$12.4M
GENE TARGETING BY VIRAL VECTORSR01DK055759 · NIDDK · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 1999 to 2017
$5.8M
GENE TARGETING STRATEGIES FOR THE TREATMENT OF OSTEOGENESIS IMPERFECTAR01AR048328 · NIAMS · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 2001 to 2010
$4.0M
Gene targeting with AAV vectors for the treatment of Osteogenesis ImperfectaK08AR053917 · NIAMS · UNIVERSITY OF WASHINGTON · PI DEYLE, DAVID R · 2008 to 2012
$658k
NHGRI NIH HHS U54 HG007010NHGRI NIH HHS U54HG007010NHLBI NIH HHS P01 HL053750NHLBI NIH HHS P01HL53750NIAMS NIH HHS K08 AR053917NIAMS NIH HHS K08AR053917NIAMS NIH HHS R01 AR048328NIAMS NIH HHS R01AR48328NIDDK NIH HHS R01 DK055759NIDDK NIH HHS R01DK55759NIGMS NIH HHS T32 GM007266
6 · The paper itself

Abstract

To determine which genomic features promote homologous recombination, we created a genome-wide map of gene targeting sites. We used an adeno-associated virus vector to target identical loci introduced as transcriptionally active retroviral vectors. A comparison of ~2,000 targeted and untargeted sites showed that targeting occurred throughout the human genome and was not influenced by the presence of nearby CpG islands, sequence repeats or DNase I-hypersensitive sites. Targeted sites were preferentially located within transcription units, especially when the target loci were transcribed in the opposite orientation to their surrounding chromosomal genes. We determined the impact of DNA replication by mapping replication forks, which revealed a preference for recombination at target loci transcribed toward an incoming fork. Our results constitute the first genome-wide screen of gene targeting in mammalian cells and demonstrate a strong recombinogenic effect of colliding polymerases.

Indexed as

DNA ReplicationGenome, HumanHomologous RecombinationTranscription, GeneticCell Line, TumorChromosome MappingCpG IslandsDeoxyribonuclease IDependovirusGenetic LociGenetic VectorsHEK293 CellsHumansDeoxyribonuclease I

Identifiers

PMID25282150
PMCPMC4405182
OpenAlexW2114375940

What OpenQuestion holds

Textmetadata
LicenceTDM
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.