Evidence map›Paper›PMID 22718833›Full record

ArticleJournal of virology2012

The threefold protrusions of adeno-associated virus type 8 are involved in cell surface targeting as well as postattachment processing.

Christina Raupp, Matthias Naumer, Oliver J Müller, Brittney L Gurda, Mavis Agbandje-McKenna, Jürgen A Kleinschmidt

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

45 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
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  5. Article
  6. Dose-finding andMolecular therapy. Methods & clinical development · 2025
    Article
  7. Article
  8. Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  9. Article
  10. Identification of a novel neutralization epitope in rhesus AAVs.Molecular therapy. Methods & clinical development · 2024
    Article
  11. Development of CNS tropic AAV1-like variants with reduced liver-targeting following systemic administration in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022
    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

6 authors at 3 institutions in 2 countries.

Christina RauppGerman Cancer Research Center, Research Program Infection and Cancer, Heidelberg, Germany.
Matthias Naumer
Oliver J Müller
Brittney L Gurda
Mavis Agbandje-McKenna
Jürgen A Kleinschmidt
Heidelberg University · DEUniversity of Florida · USGerman Cancer Research Center · DE

Funding

Structural studies of AAV capsids and their glycan receptor interactionsR01GM082946 · NIGMS · UNIVERSITY OF FLORIDA · PI ROBERT MCKENNA · 2007 to 2026
$6.1M
Antigenic structure of adeno-associated virus capsids and antibody escape mutantsR21AI072341 · NIAID · CORNELL UNIVERSITY · PI PARRISH, COLIN R. · 2007 to 2008
$417k
NIAID NIH HHS R21 AI072341NIGMS NIH HHS R01 GM082946
6 · The paper itself

Abstract

Adeno-associated virus (AAV) has attracted considerable interest as a vector for gene therapy owing its lack of pathogenicity and the wealth of available serotypes with distinct tissue tropisms. One of the most promising isolates for vector development, based on its superior gene transfer efficiency to the liver in small animals compared to AAV type 2 (AAV2), is AAV8. Comparison of the in vivo gene transduction of rAAV2 and rAAV8 in mice showed that single amino acid exchanges in the 3-fold protrusions of AAV8 in the surface loops comprised of residues 581 to 584 and 589 to 592 to the corresponding amino acids of AAV2 and vice versa had a strong influence on transduction efficiency and tissue tropism. Surprisingly, not only did conversion of AAV8 to AAV2 cap sequences increase the transduction efficiency and change tissue tropism but so did the reciprocal conversion of AAV2 to AAV8. Insertion of new peptide motifs at position 590 in AAV8 also enabled retargeting of AAV8 capsids to specific tissues, suggesting that these sequences can interact with receptors on the cell surface. However, a neutralizing monoclonal antibody that binds to amino acids (588)QQNTA(592) of AAV8 does not prevent cell binding and virus uptake, indicating that this region is not necessary for receptor binding but rather that the antibody interferes with an essential step of postattachment processing in which the 3-fold protrusion is also involved. This study supports a multifunctional role of the 3-fold region of AAV capsids in the infection process.

Indexed as

Transduction, GeneticAmino Acid MotifsAmino Acid SequenceAmino Acid SubstitutionAnimalsCapsid ProteinsCell LineDependovirusFemaleGenetic TherapyGenetic VectorsHumansMaleMiceMice, Inbred StrainsModels, MolecularCapsid Proteins

Identifiers

PMID22718833
PMCPMC3416165
OpenAlexW2041961234

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.