CoreTIA: a modular, statistically robust transduction inhibition assay for AAV neutralization
Adeno-associated virus (AAV) gene therapy is often limited by pre-existing neutralizing antibodies (NAbs), yet current assays for NAb detection lack standardization and rarely quantify uncertainty, complicating cross-study comparisons. We present coreTIA (core Transduction Inhibition Assay), a comprehensive framework providing a modular experimental protocol and a statistically robust analysis pipeline. This integrated method delivers precise, reproducible NAb titers with quantified uncertainty for every result. coreTIA's statistical framework enables robust estimation of neutralization even when dilution series are incomplete, helping to reduce repeat testing and minimizing sample volume requirements. Evaluation and refinement of key assay parameters support consistent performance across AAV serotypes. By providing a protocol and analysis suite as an open resource, coreTIA facilitates more consistent and transparent NAb measurement, potentially aiding assay harmonization and regulatory assessment, addressing a key barrier to progress in gene therapy research and development.
Authors
- Balázs Rózsa (ORCID: https://orcid.org/0000-0003-1427-7003)
- Wim Vanduffel (ORCID: https://orcid.org/0000-0002-9399-343X)
- Dániel Hillier (ORCID: https://orcid.org/0000-0003-0453-9049)
- Ferenc Mátyás (ORCID: https://orcid.org/0000-0002-3903-8896)
- Viktória Szabó (ORCID: https://orcid.org/0000-0001-6547-9102)
- István Ulbert (ORCID: https://orcid.org/0000-0001-9941-9159)
- Zsuzsanna Szemlaky
- István Hernádi (ORCID: https://orcid.org/0000-0001-7882-4817)
- Beatrix Kovács (ORCID: https://orcid.org/0000-0002-3572-4792)
- Zoltán Zsolt Nagy (ORCID: https://orcid.org/0000-0002-7330-0464)
- Fanni Somogyi
Institutions
- Semmelweis University (HU)
- Allen Institute for Brain Science (US)
- Pázmány Péter Catholic University (HU)
- Brainvest (Hungary) (HU)
- HUN-REN Institute of Experimental Medicine (HU)
- Institute of Cognitive Neuroscience and Psychology (HU)
- Neuroelectronics Research Flanders (BE)
- National Center for Epidemiology (HU)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- University of Pecs (HU)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-08-20
- DOI
- https://doi.org/10.3389/fimmu.2025.1623848
- Citations
- 3
- Primary Topic
- Virus-based gene therapy research
- Type
- article
- Field-Weighted Citation Impact
- 5.45
Funders
- Gedeon Richter
- Magyar Tudományos Akadémia
- KU Leuven
- Nemzeti Kutatási, Fejlesztési és Innovaciós Alap
- National Research, Development and Innovation Office