Evidence map›Paper›PMID 16103194›Full record

ArticleJournal of virology2005

Large-scale analysis of adeno-associated virus vector integration sites in normal human cells.

Daniel G Miller, Grant D Trobridge, Lisa M Petek, Michael A Jacobs, Rajinder Kaul, David W Russell

Abstract read
In one paragraph

Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 3 pooled it
–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, 3 syntheses or guidelines pooled it.

  1. Gene therapy for people with hepatocellular carcinoma.The Cochrane database of systematic reviews · 2024
    Pooled it
  2. Gene therapy for haemophilia.The Cochrane database of systematic reviews · 2020
    Pooled it
  3. Gene therapy for haemophilia.The Cochrane database of systematic reviews · 2016
    Pooled it
  4. Article
  5. Article
  6. Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026
    Review
  7. Article
  8. Modulation of AAV transduction and integration targeting by topoisomerase poisons.Molecular therapy. Methods & clinical development · 2024
    Article
  9. Review
  10. Review
  11. International journal of molecular sciences · 2023
    Article
  12. Molecular therapy. Nucleic acids · 2023
    Article
  13. Review
  14. Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  15. Review
  16. AAV integration in human hepatocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  17. Liver Injury Increases the Incidence of HCC following AAV Gene Therapy in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  18. Review
  19. Article
  20. Review

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

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

6 authors.

Daniel G MillerDepartment of Pediatrics, Division of Genetics and Developmental Medicine, University of Washington, Seattle, 98195-7720, USA.
Grant D Trobridge
Lisa M Petek
Michael A Jacobs
Rajinder Kaul
David W Russell

Funding

Mechanisms of Cellular Transduction with AAV VectorsK08DK062100 · NIDDK · UNIVERSITY OF WASHINGTON · PI MILLER, DANIEL G · 2002 to 2006
$626k
NIDDK NIH HHS K08 DK062100
6 · The paper itself

Abstract

The integration sites of viral vectors used in human gene therapy can have important consequences for safety and efficacy. However, an extensive evaluation of adeno-associated virus (AAV) vector integration sites has not been completed, despite the ongoing use of AAV vectors in clinical trials. Here we have used a shuttle vector system to isolate and analyze 977 unique AAV vector-chromosome integration junctions from normal human fibroblasts and describe their genomic distribution. We found a significant preference for integrating within CpG islands and the first 1 kb of genes, but only a slight overall preference for transcribed sequences. Integration sites were clustered throughout the genome, including a major preference for integration in ribosomal DNA repeats, and 13 other hotspots that contained three or more proviruses within a 500-kb window. Both junctions were localized from 323 proviruses, allowing us to characterize the chromosomal deletions, insertions, and translocations associated with vector integration. These studies establish a profile of insertional mutagenesis for AAV vectors and provide unique insight into the chromosomal distribution of DNA strand breaks that may facilitate integration.

Indexed as

Virus IntegrationChromosome MappingChromosomes, HumanDependovirusDNA-Binding ProteinsFibroblastsGenetic VectorsHumansTrans-ActivatorsCXXC1 protein, humanDNA-Binding ProteinsTrans-Activators

Identifiers

PMID16103194
PMCPMC1193581

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.