{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:03:56Z","timestamp":1790067836782,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006070","name":"Universidad de los Andes","doi-asserted-by":"publisher","award":["PVI0122029"],"award-info":[{"award-number":["PVI0122029"]}],"id":[{"id":"10.13039\/501100006070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006070","name":"Universidad de los Andes","doi-asserted-by":"publisher","award":["INV-2024-192-3135"],"award-info":[{"award-number":["INV-2024-192-3135"]}],"id":[{"id":"10.13039\/501100006070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Pre-existing neutralizing antibodies (NAbs) and total antibodies (TAbs) against adeno-associated virus (AAV) vectors represent a major barrier to the clinical translation of AAV-based gene therapies. A comprehensive characterization of their global prevalence, determinants, and clinical implications is currently lacking. We conducted a scoping review of 50 studies published between 1968 and 2026, systematically identifying seroprevalence data across AAV serotypes, populations, and geographic regions. We complemented this evidence with a structured analysis of 222 interventional AAV gene therapy trials registered in ClinicalTrials.gov, examining serotype distribution, therapeutic areas, enrollment, and immunogenicity outcomes. We found AAV2, AAV8, and AAV5 were the most extensively studied serotypes. Seroprevalence increased consistently with age and varied by geographic region, although the limited number of studies from Africa and Latin America precludes robust regional conclusions. The median trial enrollment was 14 participants, and NAb exclusion criteria markedly reduce already limited eligible populations. Long-term follow-up data indicate that declining transgene expression is frequently associated with capsid-directed cellular immunity. Standardized serological assays, region-specific seroprevalence data, and immunomodulatory strategies are essential to maximize patient eligibility and therapeutic durability in AAV gene therapy programs globally.<\/jats:p>","DOI":"10.3389\/fmed.2026.1925844","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:30:52Z","timestamp":1790065852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Global seroprevalence of neutralizing and total antibodies against AAV vectors and their impact on the clinical gene therapy landscape: a scoping review"],"prefix":"10.3389","volume":"13","author":[{"given":"Cristina","family":"S\u00e1nchez-Gutierrez","sequence":"first","affiliation":[{"name":"Institute for Biomedical Research (IIB), Department of Biological Sciences, Faculty of Sciences, Universidad de los Andes","place":["Bogot\u00e1, DC, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Fernanda","family":"Bohorquez-Zambrano","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research (IIB), Department of Biological Sciences, Faculty of Sciences, Universidad de los Andes","place":["Bogot\u00e1, DC, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Garnica-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research (IIB), Department of Biological Sciences, Faculty of Sciences, Universidad de los Andes","place":["Bogot\u00e1, DC, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin Y.","family":"Rincon","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones, Fundaci\u00f3n Cardiovascular de Colombia","place":["Floridablanca, 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