{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:11:41Z","timestamp":1790820701710,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T00:00:00Z","timestamp":1589328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103464 and P30GM114736"],"award-info":[{"award-number":["P20GM103464 and P30GM114736"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The humoral immune response elicited by adeno-associated virus (AAV)-mediated gene therapy for the treatment of mucopolysaccharidoses (MPS) poses a significant challenge to achieving therapeutic levels of transgene expression. Antibodies targeting the AAV capsid as well as the transgene product diminish the production of glycosaminoglycan (GAG)-degrading enzymes essential for the treatment of MPS. Patients who have antibodies against AAV capsid increase in number with age, serotype, and racial background and are excluded from the clinical trials at present. In addition, patients who have undergone AAV gene therapy are often excluded from the additional AAV gene therapy with the same serotype, since their acquired immune response (antibody) against AAV will limit further efficacy of treatment. Several methods are being developed to overcome this immune response, such as novel serotype design, antibody reduction by plasmapheresis and immunosuppression, and antibody evasion using empty capsids and enveloped AAV vectors. In this review, we examine the mechanisms of the anti-AAV humoral immune response and evaluate the strengths and weaknesses of current evasion strategies in order to provide an evidence-based recommendation on evading the immune response for future AAV-mediated gene therapies for MPS.<\/jats:p>","DOI":"10.3390\/ijms21103433","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T02:55:41Z","timestamp":1589424941000},"page":"3433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Evading the AAV Immune Response in Mucopolysaccharidoses"],"prefix":"10.3390","volume":"21","author":[{"given":"Matthew","family":"Piechnik","sequence":"first","affiliation":[{"name":"Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"},{"name":"Department of Medical and Molecular Sciences, University of Delaware, Newark, DE 19716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Sawamoto","sequence":"additional","affiliation":[{"name":"Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2890-0305","authenticated-orcid":false,"given":"Hidenori","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-7781","authenticated-orcid":false,"given":"Norio","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Ago","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"},{"name":"Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan"},{"name":"Department of Pediatrics, Shimane University, Shimane 690-8504, Japan"},{"name":"Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,13]]},"reference":[{"key":"ref_1","unstructured":"Scriver, C., Beaudet, A., Sly, W., and Valle, D. 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