Evidence map›Paper›PMID 14766968›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2004

DNA-dependent PK inhibits adeno-associated virus DNA integration.

Sihong Song, Yuanqing Lu, Young-Kook Choi, Yinong Han, Qiushi Tang, Ge Zhao, Kenneth I Berns, Terence R Flotte

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

55 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
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  8. Review
  9. Review
  10. Gene Therapy for Hemophilia: Facts and Quandaries in the 21st Century.Mediterranean journal of hematology and infectious diseases · 2020
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Gene augmentation for adRP mutations in RHO.Cold Spring Harbor perspectives in medicine · 2014
    Review
  17. Review
  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

8 authors at 1 institution in 1 country.

Sihong SongDepartment of Pharmaceutics, Powell Gene Therapy Center, Genetics Institute, University of Florida, Gainesville, FL 32610, USA. shsong@ufl.edu
Yuanqing Lu
Young-Kook Choi
Yinong Han
Qiushi Tang
Ge Zhao
Kenneth I Berns
Terence R Flotte
University of Florida · US

Funding

VIRAL VECTOR DELIVERY OF ANTISENSE TO ACE MRNA IN CARDIOVASCULAR DISEASEP01HL059412 · NHLBI · UNIVERSITY OF FLORIDA · PI MUZYCZKA, NICHOLAS · 1998 to 2012
$20.2M
Strategies for Sustained Effect of AAV-mediated Correction of Pompe DiseaseP01DK058327 · NIDDK · UNIVERSITY OF FLORIDA · PI CAMPBELL-THOMPSON, MARTHA · 2000 to 2009
$11.0M
Preclinical &Phase I/II Trials Of AAV-AAT VectorsR01HL069877 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FLOTTE, TERENCE R. · 2003 to 2013
$3.6M
VIRAL VECTOR DELIVERY OF ANTISENSE TO ACE MRNA IN CARDIOVASCULAR DISEASEP50HL059412 · NHLBI · UNIVERSITY OF FLORIDA · PI MUZYCZKA, NICHOLAS · 1997 to 2001
$3.0M
Anti-inflammatory Serpin(AAT and Elafin) Gene Transfers*R21DK062652 · NIDDK · UNIVERSITY OF FLORIDA · PI SONG, SIHONG · 2002 to 2003
$290k
NHLBI NIH HHS HL59412NHLBI NIH HHS HL69877NHLBI NIH HHS P01 HL059412NHLBI NIH HHS P50 HL059412NHLBI NIH HHS R01 HL069877NIDDK NIH HHS DK58327NIDDK NIH HHS DK62652NIDDK NIH HHS P01 DK058327NIDDK NIH HHS R21 DK062652
6 · The paper itself

Abstract

Recent studies have shown that recombinant adeno-associated virus (rAAV) can persist in episomal form; however, factors affecting rAAV persistence are poorly understood. DNA-dependent PK (DNA-PK) is a DNA repair enzyme, which we previously found played an important role in determining the molecular fate of the rAAV genome in mouse skeletal muscle. In the present study, we tested the effect of DNA-PK on AAV serotype 2 integration in vitro and in vivo in mouse liver. In an in vitro integration system, addition of DNA-PK decreased AAV integration, whereas antibody against DNA-PKcs increased integration. In vivo, matched doses of a recombinant AAV serotype 2 vector were injected into the portal vein of either C57BL/6 (DNA-PKcs(+/+)) or severe combined immunodeficient (DNA-PKcs(-/-)) mice. After partial hepatectomy to stimulate hepatocyte proliferation, retention of vector genomes and of transgene expression was substantially higher in severe combined immunodeficient mice, indicating that in the absence of DNA-PKcs, a greater proportion of genomes integrated into the cellular genome. In summary, we have provided evidence that DNA-PK inhibits AAV integration both in vitro and in vivo.

Indexed as

DNA-Binding ProteinsVirus IntegrationAnimalsCell LineDependovirusDNA-Activated Protein KinaseDNA, ViralGenome, ViralHepatectomyHumansLiverMaleMiceNuclear ProteinsProtein Serine-Threonine KinasesRecombination, GeneticDNA-Activated Protein KinaseDNA-Binding ProteinsDNA, ViralNuclear ProteinsPRKDC protein, humanProtein Serine-Threonine Kinases

Identifiers

PMID14766968
PMCPMC357060
OpenAlexW2013855814

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.