Evidence map›Paper›PMID 39469420›Full record

ArticleMolecular therapy. Methods & clinical development2024

Identification of a novel neutralization epitope in rhesus AAVs.

Gabriel Dagotto, Jana L Fisher, David Li, Zhenyu Li, Simon Jenni, Zongli Li, Lawrence J Tartaglia, Peter Abbink, Dan H Barouch

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Advancing AAV technology-From promise to product.Molecular therapy. Advances · 2026
    Article
  2. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  3. 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

9 authors.

Gabriel DagottoCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Jana L FisherCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
David LiCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Zhenyu LiCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Simon JenniDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
Zongli LiDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
Lawrence J TartagliaDepartment of Biological Sciences, Lehigh University, Bethlehem, PA 18015, USA.
Peter AbbinkCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Dan H BarouchCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Funding

Project 2U19AI128751 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BAROUCH, DAN H. · 2018 to 2022
$14.0M
METAGENOMICS OF ENTERIC DISEASE IN SIV-INFECTED AND UNINFECTED MACAQUESR01OD011170 · OD · WASHINGTON UNIVERSITY · PI BAROUCH, DAN H., VIRGIN, HERBERT W · 2012 to 2014
$2.3M
NIAID NIH HHS U19 AI128751NIH HHS R01 OD011170
6 · The paper itself

Abstract

Adeno-associated viruses (AAVs) are popular gene therapy delivery vectors, but their application can be limited by anti-vector immunity. Both preexisting neutralizing antibodies (NAbs) and post-administration NAbs can limit transgene expression and reduce the clinical utility of AAVs. The development of novel AAVs will advance our understanding of AAV immunity and may also have practical applications. In this study, we identified five novel AAV capsids from rhesus macaques. RhAAV4282 exhibited 91.4% capsid sequence similarity with AAV7 and showed similar tissue tropism with slightly diminished overall signal. Despite this sequence homology, RhAAV4282 and AAV7 showed limited cross-neutralization. We determined a cryo-EM structure of the RhAAV4282 capsid at 2.57 Å resolution and identified a small segment within the hypervariable region IV, involving seven amino acids that formed a shortened external loop in RhAAV4282 compared with AAV7. We generated RhAAV4282 and AAV7 mutants that involved swaps of this region and showed that this region partially determined neutralization phenotype. We termed this region the hypervariable region IV neutralizing epitope (HRNE). Our data suggests that modification of the HRNE can lead to AAVs with altered neutralization profiles.

Indexed as

AAVadeno-associated virusanti-vector immunitycapsid neutralization epitopenovel AAV capsid discoveryviral vectors

Identifiers

PMID39469420
PMCPMC11513466

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.