Evidence map›Paper›PMID 20882053›Full record

ArticleGene therapy2011

Readministration of helper-dependent adenoviral vectors to mouse airway mediated via transient immunosuppression.

H Cao, T Yang, X-F Li, J Wu, C Duan, A L Coates, J Hu

Abstract read
PubMed Publisher
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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Progress in Respiratory Gene Therapy.Human gene therapy · 2022
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Hybrid nonviral/viral vector systems for improved piggyBac DNA transposon in vivo delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2015
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Advances in cell and gene-based therapies for cystic fibrosis lung disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2012
    Review
  18. Article
  19. Review
  20. 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

7 authors at 3 institutions in 2 countries.

H CaoDepartment of Physiology and Experimental Medicine, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
T Yang
X-F Li
J Wu
C Duan
A L Coates
J Hu
Hospital for Sick Children · CAAir Force Medical University · CNChina Agricultural University · CN

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

The efficacy of adenovirus-mediated gene therapy is attenuated by the host immune responses to both vector and transgene products. Even for helper-dependent adenoviral (HD-Ad) vectors, which have all viral-coding sequences deleted, the viral capsid proteins still cause immune reactions. In order to improve the efficiency in transgene expression during HD-Ad vector readministration, we administered cyclophosphamide to transiently modulate the mouse immune system. We delivered a high dose (5 × 10(10) vector particles (vp) per mouse) of empty HD-Ad to the mouse airway to induce an initial immune response. After 4 weeks, the mice were readministered with an HD-Ad vector containing either the reporter gene, LacZ, or the gene for the human cystic fibrosis transmembrane conductance regulator (CFTR) (1.5 × 10(10) vp per mouse). We found that the expression of both transgenes was greatly improved by the administration of cyclophosphamide when compared with the expression in mice without the immunosuppressing drug. We also found that the high dose of the empty HD-Ad vector administered intranasally does not induce an acute systemic immune response, but it does elicit an acute local response of proinflammatory cytokine production. Antibodies against Ad vector, including the neutralizing antibodies, were greatly reduced by the presence of cyclophosphamide in vector readministratiton. Moreover, cyclophosphamide reduced the infiltration of inflammatory cells, including total leukocytes, lymphocytes, CD4+ and CD8+T cells. These results indicate that transient administration of immunosuppressive agent can be used to extend transgene expression as well as attenuating immunogenicity to HD-Ad vectors in airway readministration.

Indexed as

Genetic VectorsGene Transfer TechniquesAdenoviridaeAdministration, IntranasalAnimalsAntibodies, ViralCyclophosphamideCystic Fibrosis Transmembrane Conductance RegulatorDefective VirusesFemaleImmunosuppressive AgentsMiceMice, Inbred C57BLRetreatmentAntibodies, ViralCyclophosphamideCystic Fibrosis Transmembrane Conductance RegulatorImmunosuppressive Agents

Identifiers

PMID20882053
OpenAlexW1987421759

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.