Evidence map›Paper›PMID 41308640›Full record

ArticleCell reports. Medicine2025

Complete neutralizing antibody evasion by serodivergent non-mammalian AAVs enables gene therapy redosing.

Ezra J Loeb, Sophia A Fergione, Vivian Yudistyra, Marco M Fanous, Abigail R Benkert, Delaney G Fisher, Joshua A Hull, Mai K ElMallah, Aravind Asokan

Abstract read
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Trial
  2. Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. 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.

Ezra J LoebDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Sophia A FergioneDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Vivian YudistyraDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Marco M FanousDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Abigail R BenkertDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Delaney G FisherDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Joshua A HullDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Mai K ElMallahDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA.
Aravind AsokanDepartment of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA. Electronic address: aravind.asokan@duke.edu.

Funding

Advanced Immunobiology Traning Program for SurgeonsT32AI141342 · NIAID · DUKE UNIVERSITY · PI Allan D. Kirk, GEORGIA Doris TOMARAS · 2019 to 2026
$1.8M
NIAID NIH HHS T32 AI141342
6 · The paper itself

Abstract

The use of adeno-associated virus (AAV) as a gene therapy vector is significantly limited by pre-existing immunity. The high seroprevalence and broad antigenic cross-reactivity of primate-derived AAVs restrict patient eligibility and preclude therapeutic redosing. Here, we harness the phylogenetic diversity of non-mammalian dependoparvoviruses to engineer serologically distinct AAV capsids for immune evasion. A barcoded screen of divergent Dependoparvovirus isolates identifies AAV.div3A, a chimeric capsid with robust transduction, zero antigenic cross-reactivity, and undetectable seroprevalence. Derived from a phylogenetically distant Muscovy duck isolate, AAV.div3A fully evades neutralization in mice, even after passive immunization with NAb+ human serum or following initial vector dosing. Further engineering yields AAV.div3A-M1, a myotropic, liver-detargeted capsid with enhanced cardiac and diaphragm transduction. In a Pompe disease model, redosing with AAV.div3A or div3A-M1 significantly increases therapeutic GAA levels. Overall, our work leverages untapped dependoparvoviral diversity to overcome pre-existing and vector-induced immunity, enabling expansion of patient eligibility and effective redosing.

Indexed as

Antibodies, NeutralizingDependovirusGenetic TherapyImmune EvasionAnimalsAntibodies, ViralCapsidCapsid ProteinsGenetic VectorsHumansMiceAntibodies, NeutralizingAntibodies, ViralCapsid Proteinsadeno-associated viruscapsid engineeringdependoparvovirusgene therapyimmune evasionneutralizing antibodiespre-existing immunitytissue tropismvector redosing

Identifiers

PMID41308640
PMCPMC12765845

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.