Evidence map›Paper›PMID 17686840›Full record

ArticleJournal of virology2007

DNA palindromes with a modest arm length of greater, similar 20 base pairs are a significant target for recombinant adeno-associated virus vector integration in the liver, muscles, and heart in mice.

Katsuya Inagaki, Susanna M Lewis, Xiaolin Wu, Congrong Ma, David J Munroe, Sally Fuess, Theresa A Storm, Mark A Kay, Hiroyuki Nakai

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

37 citing papers in PubMed, 52 citations in OpenAlex.

  1. Targeted knock-in ofMolecular therapy. Nucleic acids · 2024
    Article
  2. Article
  3. Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023
    Review
  4. AAV integration in human hepatocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Recombinant AAV Integration Is Not Associated With Hepatic Genotoxicity in Nonhuman Primates and Patients.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Article
  14. Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Review
  15. Review
  16. Review
  17. Vector integration and tumorigenesis.Human gene therapy · 2014
    Article
  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

9 authors at 5 institutions in 2 countries.

Katsuya InagakiDepartment of Molecular Genetics & Biochemistry, University of Pittsburgh School of Medicine, W1244 BSTWR, 200 Lothrop St., Pittsburgh, PA 15261, USA.
Susanna M Lewis
Xiaolin Wu
Congrong Ma
David J Munroe
Sally Fuess
Theresa A Storm
Mark A Kay
Hiroyuki Nakai
University of Pittsburgh · USPediatrics and Genetics · USScience Applications International Corporation (United States) · USHospital for Sick Children · CAStanford University · US

Funding

HEPATIC GENE TRANSFER FOR TREATMENT OF HEMOPHILIAS A &BR01HL064274 · NHLBI · STANFORD UNIVERSITY · PI Mark A Kay · 2000 to 2026
$13.6M
Treatment of Distal Tyrosine Pathway DisordersR01DK048252 · NIDDK · OREGON HEALTH & SCIENCE UNIVERSITY · PI GROMPE, MARKUS · 1994 to 2017
$5.5M
Vector and Host Cellular Biology in AAV Vector Transduction in VivoR01DK078388 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NAKAI, HIROYUKI · 2008 to 2012
$1.4M
Establishment of the Risk of AAV Vector IntegrationR21DK068636 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NAKAI, HIROYUKI · 2004 to 2005
$296k
Vector and host cellular biology in AAV vector transduction in vivoR56DK078388 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NAKAI, HIROYUKI · 2007 to 2007
$111k
NCI NIH HHS N01 CO012400NCI NIH HHS N01-CO-12400NHLBI NIH HHS HL64274NHLBI NIH HHS R01 HL064274NIDDK NIH HHS DK68636NIDDK NIH HHS DK78388NIDDK NIH HHS R01 DK048252NIDDK NIH HHS R01 DK078388NIDDK NIH HHS R21 DK068636NIDDK NIH HHS R56 DK078388
6 · The paper itself

Abstract

Our previous study has shown that recombinant adeno-associated virus (rAAV) vector integrates preferentially in genes, near transcription start sites and CpG islands in mouse liver (H. Nakai, X. Wu, S. Fuess, T. A. Storm, D. Munroe, E. Montini, S. M. Burgess, M. Grompe, and M. A. Kay, J. Virol. 79:3606-3614, 2005). However, the previous method relied on in vivo selection of rAAV integrants and could be employed for the liver but not for other tissues. Here, we describe a novel method for high-throughput rAAV integration site analysis that does not rely on marker gene expression, selection, or cell division, and therefore it can identify rAAV integration sites in nondividing cells without cell manipulations. Using this new method, we identified and characterized a total of 997 rAAV integration sites in mouse liver, skeletal muscle, and heart, transduced with rAAV2 or rAAV8 vector. The results support our previous observations, but notably they have revealed that DNA palindromes with an arm length of greater, similar 20 bp (total length, greater, similar 40 bp) are a significant target for rAAV integration. Up to approximately 30% of total integration events occurred in the vicinity of DNA palindromes with an arm length of greater, similar 20 bp. Considering that DNA palindromes may constitute fragile genomic sites, our results support the notion that rAAV integrates at chromosomal sites susceptible to breakage or preexisting breakage sites. The use of rAAV to label fragile genomic sites may provide an important new tool for probing the intrinsic source of ongoing genomic instability in various tissues in animals, studying DNA palindrome metabolism in vivo, and understanding their possible contributions to carcinogenesis and aging.

Indexed as

Gene TargetingGenetic VectorsVirus IntegrationAdenoviridaeAnimalsBase SequenceDNAGene Transfer TechniquesHeartLiverMiceMolecular Sequence DataMusclesDNA

Identifiers

PMID17686840
PMCPMC2045527
OpenAlexW2161128756

What OpenQuestion holds

Textmetadata
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.