Evidence map›Paper›PMID 9032378›Full record

ArticleJournal of virology1997

Effect of the E4 region on the persistence of transgene expression from adenovirus vectors.

D Armentano, J Zabner, C Sacks, C C Sookdeo, M P Smith, J A St George, S C Wadsworth, A E Smith, R J Gregory

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 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
16.9field-weighted citation impact, top 1% 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

42 citing papers in PubMed, 189 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Review
  6. Gene therapy in cardiac arrhythmias.Indian pacing and electrophysiology journal · 2006
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Transcription-controlled gene therapy against tumor angiogenesis.The Journal of clinical investigation · 2004
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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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 1 institution in 1 country.

D ArmentanoGenzyme Corporation, Framingham, Massachusetts 01701-9322, USA.
J Zabner
C Sacks
C C Sookdeo
M P Smith
J A St George
S C Wadsworth
A E Smith
R J Gregory
Framingham State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The utility of adenovirus vectors for gene therapy is limited by the transience of expression that has been observed in various in vivo models. Immunological responses to viral targets can eliminate transduced cells and cause the loss of transgene expression. We previously described the characterization of an E4 modified adenovirus, Ad2E4ORF6, which is replication defective in cotton rats. We reasoned that gene transfer vectors based on Ad2E4ORF6 would have a reduced potential for viral gene expression in vivo which might be beneficial for achieving persistence of transgene expression. E1 replacement vectors expressing the cystic fibrosis transmembrane regulator or beta-galactosidase were constructed as series of vectors that differed with respect to the E4 region. Vectors containing a wild-type E4 region, E4 open reading frame 6, or a complete E4 deletion were compared in the lungs of BALB/c mice for persistence of expression. Results obtained with nude mice indicate that nonimmunological factors have a major influence on the longevity of transgene expression. Expression was transient from the E1a promoter with all vectors but persisted from the cytomegalovirus promoter only with a vector containing a wild-type E4 region. Transience of expression did not correlate with the disappearance of vector DNA, suggesting that promoter down-regulation may be involved. Coinfection studies indicate an E4 product(s) could be supplied in trans to allow persistent expression from the cytomegalovirus promoter. In summary, the choice of promoter is important for achieving persistence of expression; in addition, some promoters are highly influenced by the context of the vector backbone.

Indexed as

Gene Expression RegulationGenetic VectorsTransgenesAdenoviridaeAdenovirus E1A ProteinsAdenovirus E4 ProteinsAnimalsbeta-GalactosidaseCell Line, TransformedCystic Fibrosis Transmembrane Conductance RegulatorCytomegalovirusLiverMiceMice, Inbred BALB CMice, NudePromoter Regions, GeneticAdenovirus E1A ProteinsAdenovirus E4 Proteinsbeta-GalactosidaseCystic Fibrosis Transmembrane Conductance Regulator

Identifiers

PMID9032378
PMCPMC191351
OpenAlexW2133753843

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.