Evidence map›Paper›PMID 21525953›Full record

ArticleGene therapy2011

Self-inactivating helper virus for the production of high-capacity adenoviral vectors.

M Gonzalez-Aparicio, I Mauleon, P Alzuguren, M Bunuales, G Gonzalez-Aseguinolaza, C San Martín, J Prieto, R Hernandez-Alcoceba

Open access · bronzeAbstract 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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.6field-weighted citation impact, top 27% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Transfer ofMolecular therapy. Nucleic acids · 2021
    Article
  5. Article
  6. Article
  7. Viral vector platforms within the gene therapy landscape.Signal transduction and targeted therapy · 2021
    Review
  8. High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020
    Review
  9. Genes · 2019
    Article
  10. Review
  11. Article
  12. Article
  13. Immunological landscape and immunotherapy of hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2015
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. 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 3 institutions in 1 country.

M Gonzalez-AparicioDivision of Hepatology and Gene Therapy, CIMA, University of Navarra, Foundation for Applied Medical Research, Pamplona, Spain.
I Mauleon
P Alzuguren
M Bunuales
G Gonzalez-Aseguinolaza
C San Martín
J Prieto
R Hernandez-Alcoceba
Universidad de Navarra · ESCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESCentro Nacional de Biotecnología · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Standard methods for producing high-capacity adenoviral vectors (HC-Ads) are based on co-infection with a helper adenovirus (HV). To avoid HV encapsidation, its packaging signal (Ψ) is flanked by recognition sequences for recombinases expressed in the producing cells. However, accumulation of HV and low yield of HC-Ad are frequently observed, due in part to insufficient recombinase expression. We describe here a novel HV (AdTetCre) in which Ψ is flanked by loxP sites that can be excised by a chimeric MerCreMer recombinase encoded in the same viral genome. Efficient modulation of cleavage was obtained by simultaneous control of MerCreMer expression using a tet-on inducible system, and translocation to the nucleus by 4-hydroxytamoxifen (TAM). Encapsidation of AdTetCre was strongly inhibited by TAM plus doxycicline. Using AdTetCre and 293Cre4 cells for the production of HC-Ads, we found that cellular and virus-encoded recombinases cooperate to minimize HV contamination. The method was highly reproducible and allowed the routine production of different HC-Ads in a medium-scale laboratory setting in adherent cells, with titers >10¹⁰ infectious units and <0.1% HV contamination. The residual HVs lacked Ψ and were highly attenuated. We conclude that self-inactivating HVs based on virally encoded recombinases are promising tools for the production of HC-Ads.

Indexed as

AdenoviridaeDoxycyclineGenetic TherapyGenetic VectorsHelper VirusesIntegrasesTamoxifenafimoxifeneCre recombinaseDoxycyclineIntegrasesTamoxifen

Identifiers

PMID21525953
OpenAlexW2071713682

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.