Evidence map›Paper›PMID 15815705›Full record

ArticleGene therapy2005

Engineered E. coli delivers therapeutic genes to the colonic mucosa.

I Castagliuolo, E Beggiao, P Brun, L Barzon, S Goussard, R Manganelli, C Grillot-Courvalin, G Palù

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–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

22 citing papers in PubMed.

  1. Diagnosing and engineering gut microbiomes.EMBO molecular medicine · 2024
    Review
  2. Genetically Engineered Microorganisms and Their Impact on Human Health.International journal of clinical practice · 2024
    Review
  3. Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment.Frontiers in bioengineering and biotechnology · 2021
    Review
  4. Review
  5. Recent trends and advances in microbe-based drug delivery systems.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2019
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Hybrid biosynthetic gene therapy vector development and dual engineering capacity.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
  11. Article
  12. Article
  13. Functional motifs in Escherichia coli NC101.International journal of molecular and cellular medicine · 2013
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Biological gene delivery vehicles: beyond viral vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2009
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors.

I CastagliuoloDepartment of Histology, Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy.
E Beggiao
P Brun
L Barzon
S Goussard
R Manganelli
C Grillot-Courvalin
G Palù

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Taking advantage of the proximity of bowel mucosa to luminal bacteria, we have attempted to deliver a therapeutic gene to the colonic mucosa by oral administration of an invasive and non-pathogenic Escherichia coli. E. coli diamenopimelate (dap) auxotroph, harboring plasmid pGB2Omegainv-hly, express the inv gene from Yersinia pseudotubercolosis that confers the ability to invade nonprofessional phagocytic cells and the hly gene from Listeria monocytogenes that allows expression of lystreriolysin O, a perforin cytolysin able to perfore phagosomal membranes. This bacterial vector invades and transfers functional DNA to epithelial cells in vitro. We have shown that this strain carrying a therapeutic gene (pC1OmegaTGF-beta1) can significantly reduce the severity of experimental colitis in mice. However, as a consequence of mucosal barrier disruption during colitis, vector-specific mRNA transcripts could be recovered from the colon and also from extra-colonic tissues. We therefore replaced the constitutive CMV promoter in pC1OmegaTGF-beta1 by the inflammation-inducible interleukin-8 promoter generating plasmid pC1OmegaTGF-beta1IND. Plasmid-specific TGF-beta1 mRNA transcripts were detectable in mouse CMT-93 epithelial cells incubated with E. coli BM2710/pGB2Omegainv-hly carrying pC1OmegaTGF-beta1IND following exposure to inflammatory cytokines. Furthermore, the transcripts were detectable only within inflamed tissues and the therapeutic effects were comparable to those in animals treated with E. coli BM2710/pGB2Omegainv-hly+pC1OmegaTGF-beta1. In summary, engineered enteric bacteria can efficiently deliver in vivo therapeutic genes to the intact intestinal mucosa and regulation expression of the therapeutic gene by an inflammation-inducible promoter prevents its dissemination during colitis.

Indexed as

Administration, OralAnimalsBacterial ToxinsColitisColonEpithelial CellsEscherichia coli ProteinsGene Expression RegulationGenetic EngineeringGenetic TherapyGenetic VectorsHeat-Shock ProteinsHemolysin ProteinsIntestinal AbsorptionIntestinal MucosaListeria monocytogenesBacterial ToxinsEscherichia coli ProteinsHeat-Shock ProteinsHemolysin ProteinshlyA protein, Listeria monocytogenesTgfb1 protein, mouseTransforming Growth Factor betaTransforming Growth Factor beta1

Identifiers

PMID15815705

What OpenQuestion holds

Textmetadata
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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.