Evidence map›Paper›PMID 41775734›Full record

ArticleNature communications2026

Integrated computational and experimental immunoengineering of adeno-associated virus capsid T cell epitopes in mice.

Sojin Bing, Arya Eskandarian, Sean Smith, Abdul Mohin Sajib, Stephanee Warrington, Sima Saleh, Susana S Najera, Rebecca J D'Esposito, Luis Santana-Quintero, Ronit Mazor

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Sojin BingOffice of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.
Arya EskandarianOffice of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.
Sean SmithOffice of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.
Abdul Mohin SajibOffice of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.
Stephanee WarringtonOffice of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.
Sima SalehOffice of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.
Susana S NajeraOffice of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-3441-8013
Rebecca J D'EspositoWaters Corporation, Milford, MA, USA.
Luis Santana-QuinteroOffice of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-4290-1021
Ronit MazorOffice of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U. S. Food and Drug Administration, Silver Spring, MD, USA. ronit.mazor@fda.hhs.gov.ORCID http://orcid.org/0000-0002-5456-1247

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adeno-associated virus (AAV) vectors are widely used in gene therapy, but their immunogenicity remains a significant challenge, limiting long-term efficacy and the feasibility of repeated administration. In this study, we combine computational prediction with experimental validation to engineer AAV9 capsids with reduced immunogenicity. To facilitate this, we developed the Epitope Modification and MHC Prediction (EMMP) pipeline, which systematically automates the evaluation of amino acid substitutions for their predicted effects on major histocompatibility complex (MHC) presentability. Using this pipeline, we modify a CD4⁺ T-cell epitope in the AAV9 capsid that is identified and characterized as a proof-of-concept. Two mutant variants, R312H and R312Q, are selected and evaluated for transduction efficiency in vitro and immune response modulation in vivo. Notably, R312Q shows a significant reduction in T-cell activation and anti-AAV9 antibody production, albeit with a slight reduction in transduction at low multiplicities of infection (MOI). These results demonstrate a rational approach for optimizing AAV vector design, with potential applications for improving the safety and efficacy of gene therapy.

Indexed as

CapsidCapsid ProteinsDependovirusEpitopes, T-LymphocyteAnimalsCD4-Positive T-LymphocytesGenetic TherapyGenetic VectorsHumansImmunoinformaticsLymphocyte ActivationMiceMice, Inbred C57BLTransduction, GeneticCapsid ProteinsEpitopes, T-Lymphocyte

Identifiers

PMID41775734
PMCPMC13065821

What OpenQuestion holds

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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.