Evidence map›Paper›PMID 17344904›Full record

ArticleGene therapy2007

Electroporation-mediated transfer of plasmids to the lung results in reduced TLR9 signaling and inflammation.

R Zhou, J E Norton, N Zhang, D A Dean

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
6.2field-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

19 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Toll-like receptor 9 partially regulates lung inflammation induced following exposure to chicken barn air.Journal of occupational medicine and toxicology (London, England) · 2016
    Article
  7. Article
  8. Electroporation-mediated gene delivery.Advances in genetics · 2015
    Article
  9. Review
  10. Article
  11. Gene therapy for ALI/ARDS.Critical care clinics · 2011
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
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

4 authors at 1 institution in 1 country.

R ZhouDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
J E Norton
N Zhang
D A Dean
Northwestern University · US

Funding

Role of LUBAC and Na K-ATPase in Acute Lung InjuryP01HL071643 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHANDEL, NAVDEEP S · 2003 to 2019
$30.8M
Alveolar Epithelial Cell-Specific Gene Therapy PlasmidsR01HL081148 · NHLBI · UNIVERSITY OF ROCHESTER · PI DEAN, DAVID A · 2006 to 2010
$1.8M
VASCULAR SMOOTH MUSCLE SPECIFIC GENE THERAPY VECTORSR01HL059956 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI DEAN, DAVID A · 1998 to 2007
$1.8M
NHLBI NIH HHS HL59956NHLBI NIH HHS HL71643NHLBI NIH HHS HL81148NHLBI NIH HHS P01 HL071643NHLBI NIH HHS R01 HL059956NHLBI NIH HHS R01 HL081148
6 · The paper itself

Abstract

Electroporation can deliver DNA efficiently and safely to tissues in live animals, including the lung where it causes little inflammation or lung injury. In contrast, cationic lipid-mediated gene transfer has been shown to induce an inflammatory response caused by unmethylated plasmid CpG residues, which activate the toll-like receptor (TLR9) signaling pathway. As TLR9 is located in the endosomal/lysosomal compartment, we hypothesized that plasmids do not activate TLR9 during electroporation because they enter the cytoplasm directly through transient pores in the plasma membrane. To test this, plasmids were transfected into kidney epithelial cells overexpressing TLR9 (HEK293-TLR9+) and cells lacking TLR9 (HEK293-TLR9-null). Interleukin (IL)-8 expression, an indicator of TLR9 activation, increased more than 10-fold at 24 h post-liposome transfection in HEK293-TLR9+ cells, but showed no significant increase in electroporated cells, compared with untransfected cells. In vivo liposome-mediated gene transfer caused increases in IL-6, IL-12, tumor necrosis factor alpha and interferon gamma in mouse bronchial alveolar lavage fluid, whereas the levels of these cytokines were more than 10-fold lower by comparison following electroporation. Depletion of alveolar macrophages suggested that this inflammatory response is mediated by resident pulmonary epithelial cells. These results suggest that electroporation-mediated gene transfer bypasses the TLR-9 pathway, thus accounting for the low levels of inflammation seen with this approach.

Indexed as

Cell LineDNAElectroporationGenetic TherapyHumansKidneySignal TransductionToll-Like Receptor 9DNAToll-Like Receptor 9

Identifiers

PMID17344904
PMCPMC4150868
OpenAlexW2066634041

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.