{
  "abstract": "Mucopolysaccharidosis IVA (MPS IVA) results from deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to progressive keratan sulfate accumulation, and current treatments have limited efficacy. Although adeno-associated virus (AAV) gene therapy can restore systemic enzyme activity, immune responses to the transgene and viral capsid restrict durability and prevent vector re-administration. We evaluated a combined strategy of antigen-specific oral immune tolerance and sequential AAV serotype delivery. Neonatal MPS IVA mice received a mixture of three immunodominant GALNS-derived T- and B-cell epitopes on alternate days for 20 days, followed by AAV9 at 4 weeks and redosing with either AAV9 or AAV8 at 10 weeks. Peptide-treated tolerized MPS IVA mice showed a 2–3-fold increase in circulating GALNS activity after the first dose and a 7–8-fold increase after redosing, whereas non-tolerized MPS IVA mice developed anti-GALNS antibodies that reduced enzyme levels. No cross-reactive neutralizing antibodies were detected between AAV9 and AAV8. Peptide-treated mice showed normalization of plasma and hepatic keratan sulfate (KS) and significant improvements in skeletal and cardiac histopathology, with the greatest benefit in the peptide-treated AAV9→AAV8 group. These findings demonstrate that oral immune tolerance enables safe AAV re-administration, enhances systemic enzyme bioavailability, and improves tissue correction, supporting a clinically translatable approach for durable treatment of MPS IVA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA",
    "Department of Biomedical Research, Nemours Children’s Health, Wilmington, DE 19803, USA",
    "Department of Pediatrics, Shimane University, Izumo 693-8501, Japan",
    "Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan",
    "Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA 19107, USA",
    "Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA",
    "DuPont Experimental Station, Bldg. E400 #5205, 200 Powder Mill Rd., Wilmington, DE 19803, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sampurna Saikia"
    },
    {
      "affs": [
        1
      ],
      "name": "Krishna Sai Musini",
      "orcid": "0000-0002-0314-462X"
    },
    {
      "affs": [
        1
      ],
      "name": "Shaukat Khan"
    },
    {
      "affs": [
        1,
        2,
        3,
        4,
        5,
        6
      ],
      "name": "Shunji Tomatsu",
      "orcid": "0000-0002-0673-2160"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9va6xcjj8aqqt.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219553",
  "fulltext_url": null,
  "id": "9va6xcjj8aqqt",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9553",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Lysosomal Storage Disorders Research"
    ]
  ],
  "openalex": "W7223831451",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/9va6xcjj8aqqt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219553",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9553"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Lysosomal Storage Disorders Research",
      "subfield": "physiology"
    }
  ],
  "title": "Induction of Oral Immune Tolerance Enables Sequential AAV9/AAV8 Gene Therapy in Mucopolysaccharidosis IVA",
  "title_text": "Induction of Oral Immune Tolerance Enables Sequential AAV9/AAV8 Gene Therapy in Mucopolysaccharidosis IVA",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/9va6xcjj8aqqt",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}