Evidence map›Paper›PMID 14973543›Full record

ArticleGene therapy2004

An inflammation-inducible adenoviral expression system for local treatment of the arthritic joint.

F A J van de Loo, A S K de Hooge, R L Smeets, A C Bakker, M B Bennink, O J Arntz, L A B Joosten, H M van Beuningen, P K van der Kraan, A W Varley and 1 more

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.5field-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

25 citing papers in PubMed, 58 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. IL10 released by a new inflammation-regulated lentiviral system efficiently attenuates zymosan-induced arthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2013
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Orthopedic gene therapy in 2008.Molecular therapy : the journal of the American Society of Gene Therapy · 2009
    Review
  18. Gene therapy of the rheumatic diseases: 1998 to 2008.Arthritis research & therapy · 2009
    Review
  19. Gene therapy for arthritis.Modern rheumatology · 2008
    Review
  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

11 authors at 3 institutions in 2 countries.

F A J van de LooRheumatology Research and Advanced Therapeutic, University Medical Center Nijmegen, Nijmegen, The Netherlands.
A S K de Hooge
R L Smeets
A C Bakker
M B Bennink
O J Arntz
L A B Joosten
H M van Beuningen
P K van der Kraan
A W Varley
W B van den Berg
Radboud University Medical Center · NLRadboud University Nijmegen · NLThe University of Texas Southwestern Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To achieve a disease-regulated transgene expression for physiologically responsive gene therapy of arthritis, a hybrid promoter was constructed. The human IL-1 beta enhancer region (-3690 to -2720) upstream of the human IL-6 promoter region (-163 to +12) was essential in mounting a robust response in HIG-82 synovial fibroblasts and in RAW 264,7 macrophages. A replication-deficient adenovirus was engineered with luciferase (Luc) controlled by the IL-1/IL-6 promoter (Ad5.IL-1/IL-6-Luc). LPS caused a 23- and 4.6-fold induction of Luc. activity in RAW cells infected with Ad5.IL-1/IL-6-Luc or the conventional Ad5.CMV-Luc construct, respectively. Next, adenoviruses (10(6) ffu) were injected into the knees of C57Bl/6 mice. An intra-articular injection of zymosan, 3 days after Ad5.IL-1/IL-6-Luc, increased Luc. activity by 39-fold but had no effect in the Ad5.CMV-Luc joints. The constitutive CMV promoter was rapidly silenced and could not be reactivated in vivo. In contrast, the IL-1/IL-6 promoter could be reactivated by Streptococcal cell wall (SCW)-induced arthritis up to 21 days after infection. Next the IL-1/IL-6 promoter was compared to the C3-Tat/HIV-LTR two-component system in wild-type, IL-6(-/-) and IL-1(-/-) gene knockout mice. Both systems responded well to LPS-, zymosan- and SCW-induced arthritis. However, the basal activity of the IL-1/IL-6 promoter was lower and IL-6 independent. This study showed that the IL-1/IL-6 promoter is feasible to achieve disease-regulated transgene expression for treatment of arthritis.

Indexed as

Promoter Regions, GeneticAdenoviridaeAnimalsAntigens, BacterialArthritis, InfectiousCytokinesGene Expression RegulationGenetic TherapyGenetic VectorsInjections, Intra-ArticularInterleukin-1Interleukin-6LipopolysaccharidesMaleMiceMice, Inbred C57BLAntigens, BacterialCytokinesInterleukin-1Interleukin-6LipopolysaccharidesZymosan

Identifiers

PMID14973543
OpenAlexW2115332379

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.