Evidence map›Paper›PMID 21179172›Full record

ArticleGene therapy2011

Construction of a novel expression cassette for increasing transgene expression in vivo in endothelial cells of large blood vessels.

N Dronadula, L Du, R Flynn, J Buckler, J Kho, Z Jiang, S Tanaka, D A Dichek

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Apolipoprotein A-I vascular gene therapy reduces vein-graft atherosclerosis.Molecular therapy. Methods & clinical development · 2023
    Article
  4. Article
  5. In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium.Journal of visualized experiments : JoVE · 2018
    Article
  6. Article
  7. Review
  8. Article
  9. Molecular-genetic imaging of cancer.Advances in cancer research · 2014
    Review
  10. Article
  11. Expression of apolipoprotein A-I in rabbit carotid endothelium protects against atherosclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2011
    Article
  12. Article
  13. 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 2 institutions in 1 country.

N DronadulaDepartment of Medicine, University of Washington, Seattle, WA 98195-7710, USA.
L Du
R Flynn
J Buckler
J Kho
Z Jiang
S Tanaka
D A Dichek
Seattle University · USUniversity of Washington · US

Funding

Engineering Blood Vessels to Resist AtherosclerosisR01HL076226 · NHLBI · UNIVERSITY OF WASHINGTON · PI DICHEK, DAVID A · 2006 to 2009
$2.1M
Howard Hughes Medical InstituteNHLBI NIH HHS HL076226NHLBI NIH HHS R01 HL076226
6 · The paper itself

Abstract

The success of gene therapy hinges on achievement of adequate transgene expression. To ensure high transgene expression, many gene-therapy vectors include highly active virus-derived transcriptional elements. Other vectors include tissue-specific eukaryotic transcriptional elements, intended to limit transgene expression to specific cell types, avoid toxicity and prevent immune responses. Unfortunately, tissue specificity is often accompanied by lower transgene expression. Here, we use eukaryotic (murine) transcriptional elements and a virus-derived posttranscriptional element to build cassettes designed to express a potentially therapeutic gene (interleukin (IL)-10) in large-vessel endothelial cells (ECs) at levels as high as obtained with the cytomegalovirus (CMV) immediate early promoter, while retaining EC specificity. The cassettes were tested by incorporation into helper-dependent adenoviral vectors, and transduction into bovine aortic EC in vitro and rabbit carotid EC in vivo. The murine endothelin-1 promoter showed EC specificity, but expressed only 3% as much IL-10 mRNA as CMV. Inclusion of precisely four copies of an EC-specific enhancer and a posttranscriptional regulatory element increased IL-10 expression to a level at or above the CMV promoter in vivo, while retaining--and possibly enhancing--EC specificity, as measured in vitro. The cassette reported here will likely be useful for maximizing transgene expression in large-vessel EC, while minimizing systemic effects.

Indexed as

Carotid ArteriesGene Transfer TechniquesAdenoviridaeAnimalsCattleCell LineCytomegalovirusDefective VirusesEndothelial CellsGenetic VectorsInterleukin-10MiceOrgan SpecificityPromoter Regions, GeneticRabbitsRegulatory Sequences, Nucleic AcidInterleukin-10

Identifiers

PMID21179172
PMCPMC3093449
OpenAlexW2047867982

What OpenQuestion holds

Textmetadata
LicenceTDM
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.