Evidence map›Paper›PMID 30842485›Full record

ArticleScientific reports2019

Vector uncoating limits adeno-associated viral vector-mediated transduction of human dendritic cells and vector immunogenicity.

Axel Rossi, Léa Dupaty, Ludovic Aillot, Liang Zhang, Célia Gallien, Michael Hallek, Margarete Odenthal, Sahil Adriouch, Anna Salvetti, Hildegard Büning

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Article
  3. Development of a gene-activated matrix for enhanced AAV gene deliveryFrontiers in bioengineering and biotechnology · 2026
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  11. Review
  12. T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  13. Resolving hidden subpopulations of filled AAVs by probing capsid integrity.Molecular therapy. Methods & clinical development · 2024
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Modifying immune responses to adeno-associated virus vectors by capsid engineering.Molecular therapy. Methods & clinical development · 2023
    Article
  19. Article
  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

10 authors at 4 institutions in 2 countries.

Axel RossiInternational Center for Research in Infectiology (CIRI), INSERM U1111 - Université claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieur de Lyon, Université de Lyon, Lyon, France.
Léa DupatyNormandie Univ, UNIROUEN, INSERM, U1234, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes (PANTHER), 76000, Rouen, France.
Ludovic AillotInternational Center for Research in Infectiology (CIRI), INSERM U1111 - Université claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieur de Lyon, Université de Lyon, Lyon, France.
Liang ZhangCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Célia GallienInternational Center for Research in Infectiology (CIRI), INSERM U1111 - Université claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieur de Lyon, Université de Lyon, Lyon, France.
Michael HallekClinic I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
Margarete OdenthalInstitute of Pathology, University Hospital Cologne, Cologne, Germany.
Sahil AdriouchNormandie Univ, UNIROUEN, INSERM, U1234, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes (PANTHER), 76000, Rouen, France. sahil.adriouch@univ-rouen.fr.ORCID 0000-0002-0265-7773
Anna SalvettiInternational Center for Research in Infectiology (CIRI), INSERM U1111 - Université claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Supérieur de Lyon, Université de Lyon, Lyon, France. anna.salvetti@inserm.fr.ORCID 0000-0003-2007-8350
Hildegard BüningInstitute of Experimental Hematology, Hannover Medical School, Hannover, Germany. buening.hildegard@mh-hannover.de.
Université Claude Bernard Lyon 1 · FRInserm · FRUniversity Hospital Cologne · DEUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV's low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV's intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV's in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8

Indexed as

Transduction, GeneticAnimalsCapsidCapsid ProteinsCD8-Positive T-LymphocytesDendritic CellsDependovirusGenetic VectorsHumansMaleMiceMice, Inbred C57BLCapsid Proteins

Identifiers

PMID30842485
PMCPMC6403382
OpenAlexW2918328056

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.