Evidence map›Paper›PMID 26125605›Full record

ArticleGene therapy2015

Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

C Unzu, I Melero, S Hervás-Stubbs, A Sampedro, U Mancheño, A Morales-Kastresana, I Serrano-Mendioroz, R E de Salamanca, A Benito, A Fontanellas

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.5field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Targeted adenovirus-mediated transduction of human T cellsMolecular therapy. Methods & clinical development · 2023
    Article
  3. Review
  4. Gene therapy approaches for equine osteoarthritis.Frontiers in veterinary science · 2022
    Review
  5. High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020
    Review
  6. Article
  7. Article
  8. 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

10 authors at 4 institutions in 2 countries.

C UnzuPediatric Surgery Laboratory, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
I MeleroImmunotherapy and Hepatology Area, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
S Hervás-StubbsImmunotherapy and Hepatology Area, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
A SampedroImmunotherapy and Hepatology Area, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
U MancheñoImmunotherapy and Hepatology Area, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
A Morales-KastresanaImmunotherapy and Hepatology Area, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
I Serrano-MendiorozImmunotherapy and Hepatology Area, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
R E de SalamancaResearch Center, Hospital Universitario 12 de Octubre, University Complutense of Madrid, Madrid, Spain.
A BenitoInstituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
A FontanellasImmunotherapy and Hepatology Area, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Universidad de Navarra · ESNavarre Institute of Health Research · ESHospital Universitario 12 De Octubre · ESUniversity of Geneva · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

Indexed as

Gene Transfer TechniquesTransgenesAdenoviridaeAnimalsGene ExpressionGenetic TherapyGenetic VectorsHelper VirusesHumansHydroxymethylbilane SynthaseImmunosuppressive AgentsLiverMacaca fascicularisMaleHydroxymethylbilane SynthaseImmunosuppressive Agents

Identifiers

PMID26125605
OpenAlexW1605337640

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.