{
  "abstract": "Coagulation factor VIII (FVIII) is a key therapeutic protein for hemophilia A, an inherited bleeding disorder caused by FVIII deficiency or dysfunction. The development and production of FVIII-based therapeutics remains challenging due to the intrinsic complexity of FVIII biosynthesis, folding, secretion, and functional stability. Advances in the understanding of the FVIII life cycle, as well as studies of its natural homologs, have created opportunities to develop improved FVIII variants. In parallel, therapeutic strategies to restore FVIII activity have evolved from replacement therapy with exogenous FVIII to gene-based delivery of a functional F8 copy. Among these approaches, AAV-mediated gene therapy has emerged as a clinically viable platform with a generally favorable safety profile, prompting the development of multiple therapeutic candidates for hemophilia A. This review summarizes established and current knowledge of FVIII structure, biosynthesis, and immunology in the context of developing effective and clinically applicable AAV-mediated therapies for hemophilia A. Particular attention is given to engineered FVIII variants and the latest clinical findings in AAV gene therapy, as well as to long-term efficacy and safety.",
  "abstract_shown": true,
  "affiliations": [
    "Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow 125315, Russia",
    "Moscow Center for Advanced Studies, Kulakova str. 20, Moscow 123592, Russia",
    "Morozov’s Moscow City Children Clinical Hospital, Beregovoy Proezd 5A/1, Moscow 121087, Russia",
    "Moscow Clinical Scientific Center N.A. A.S. Loginov, Moscow 111123, Russia"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Albina Khairetdinova",
      "orcid": "0009-0004-5981-0697"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Valentin Artemyev",
      "orcid": "0009-0001-1774-6656"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ekaterina A. Astakhova"
    },
    {
      "affs": [
        0
      ],
      "name": "Syune Ambaryan",
      "orcid": "0000-0003-4439-9247"
    },
    {
      "affs": [
        0
      ],
      "name": "Matvey Pilagov",
      "orcid": "0000-0002-1915-382X"
    },
    {
      "affs": [
        1
      ],
      "name": "Anna Maznina"
    },
    {
      "affs": [
        2
      ],
      "name": "Victoria S. Lobanova",
      "orcid": "0000-0002-3764-2766"
    },
    {
      "affs": [
        0
      ],
      "name": "Sofya G. Feoktistova"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Olga N. Mityaeva",
      "orcid": "0000-0001-9252-1601"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Pavel Yu. Volchkov"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eeydbzsq0hzrt.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219928",
  "fulltext_url": null,
  "id": "eeydbzsq0hzrt",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9928",
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/eeydbzsq0hzrt.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T00:21:14Z",
      "native_id": "10.3390/ijms27219928",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9928"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Engineered Factor VIII: A Comprehensive Review of Molecular Biology, Design Strategies, and AAV-Mediated Gene Therapy",
  "title_text": "Engineered Factor VIII: A Comprehensive Review of Molecular Biology, Design Strategies, and AAV-Mediated Gene Therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:21:12Z",
  "url": "https://research.draconitic.com/paper/eeydbzsq0hzrt",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}