Evidence map›Paper›PMID 9343199›Full record

ArticleJournal of virology1997

Adeno-associated virus vector integration junctions.

E A Rutledge, D W Russell

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

60 citing papers in PubMed, 133 citations in OpenAlex.

  1. Article
  2. Article
  3. Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023
    Review
  4. 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
  5. AAV integration in human hepatocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  6. Review
  7. Review
  8. A Molecular Revolution in the Treatment of Hemophilia.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Review
  9. Review
  10. Article
  11. Review
  12. Hemophilia gene therapy comes of age.Hematology. American Society of Hematology. Education Program · 2017
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. 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

2 authors at 1 institution in 1 country.

E A RutledgeDepartment of Medicine and Markey Molecular Medicine Center, University of Washington, Seattle 98195, USA.
D W Russell
University of Washington · US

Funding

VECTOR CONSTRUCTIONS FOR GENE THERAPY OF SICKLE CELL DISEASEP01HL053750 · NHLBI · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 1994 to 2014
$30.4M
RETROVIRAL TRANSDUCTION OF NON-DIVIDING CELLSK08HL003100 · NHLBI · UNIVERSITY OF WASHINGTON · PI RUSSELL, DAVID W · 1994 to 1996
–
NHLBI NIH HHS K08 HL03100NHLBI NIH HHS P01 HL53750
6 · The paper itself

Abstract

Vectors derived from adeno-associated virus (AAV) have the potential to stably transduce mammalian cells by integrating into host chromosomes. Despite active research on the use of AAV vectors for gene therapy, the structure of integrated vector proviruses has not previously been analyzed at the DNA sequence level. Studies on the integration of wild-type AAV have identified a common site-specific integration locus on human chromosome 19; however, most AAV vectors do not appear to integrate at this locus. To improve our understanding of AAV vector integration, we analyzed the DNA sequences of several integrated vector proviruses. HeLa cells were transduced with an AAV shuttle vector, and integrated proviruses containing flanking human DNA were recovered as bacterial plasmids for further analysis. We found that AAV vectors integrated as single-copy proviruses at random chromosomal locations and that the flanking HeLa DNA at integration sites was not homologous to AAV or the site-specific integration locus of wild-type AAV. Recombination junctions were scattered throughout the vector terminal repeats with no apparent site specificity. None of the integrated vectors were fully intact. Vector proviruses with nearly intact terminal repeats were excised and amplified after infection with wild-type AAV and adenovirus. Our results suggest that AAV vectors integrate by nonhomologous recombination after partial degradation of entering vector genomes. These findings have important implications for the mechanism of AAV vector integration and the use of these vectors in human gene therapy.

Indexed as

Genetic VectorsVirus IntegrationBase SequenceChromosome MappingDependovirusHeLa CellsHumansMolecular Sequence DataNucleic Acid ConformationPlasmidsProvirusesTransduction, Genetic

Identifiers

PMID9343199
PMCPMC192305
OpenAlexW1702771419

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.