Evidence map›Paper›PMID 30089698›Full record

ArticleJournal of virology2018

Mapping an Adeno-associated Virus 9-Specific Neutralizing Epitope To Develop Next-Generation Gene Delivery Vectors.

April R Giles, Lakshmanan Govindasamy, Suryanarayan Somanathan, James M Wilson

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

28 citing papers in PubMed, 41 citations in OpenAlex.

  1. Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  2. Article
  3. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
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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

4 authors at 1 institution in 1 country.

April R GilesGene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Lakshmanan GovindasamyGene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Suryanarayan SomanathanGene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
James M WilsonGene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA wilsonjm@upenn.edu.
University of Pennsylvania · US

Funding

VECTOR COREP01HL059407 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI JOHNSTON, JULIE · 1999 to 2019
$35.6M
NHLBI NIH HHS P01 HL059407
6 · The paper itself

Abstract

Recent clinical trials have demonstrated the potential of adeno-associated virus (AAV)-based vectors for treating rare diseases. However, significant barriers remain for the translation of these vectors into widely available therapies. In particular, exposure to the AAV capsid can generate an immune response of neutralizing antibodies. One approach to overcome this response is to map the AAV-specific neutralizing epitopes and rationally design an AAV capsid able to evade neutralization. To accomplish this, we isolated a monoclonal antibody against AAV9 following immunization of BALB/c mice and hybridoma screening. This antibody, PAV9.1, is specific for intact AAV9 capsids and has a high neutralizing titer of >1:160,000. We used cryo-electron microscopy to reconstruct PAV9.1 in complex with AAV9. We then mapped its epitope to the 3-fold axis of symmetry on the capsid, specifically to residues 496-NNN-498 and 588-QAQAQT-592. Capsid mutagenesis demonstrated that even a single amino acid substitution within this epitope markedly reduced binding and neutralization by PAV9.1. In addition,

Indexed as

Epitope MappingGenetic VectorsGene Transfer TechniquesAnimalsAntibodies, MonoclonalAntibodies, NeutralizingCapsidCryoelectron MicroscopyDependovirusDNA Mutational AnalysisEpitopesMice, Inbred BALB CMice, Inbred C57BLUnited StatesViral TropismAntibodies, MonoclonalAntibodies, NeutralizingEpitopesadeno-associated virusgene therapyneutralizing antibodystructural biologyvector engineering

Identifiers

PMID30089698
PMCPMC6158442
OpenAlexW2886127363

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.