{
  "abstract": "Retinitis pigmentosa (RP) affects 1 in 3,000 individuals worldwide, with 30%–40% of cases inherited as autosomal dominant (AD). Mutations in RHO (RP4) are the most common cause of ADRP. Because most RHO mutations exert gain-of-function or dominant-negative effects, conventional gene supplementation is insufficient, requiring mutant allele inactivation. Allele-specific editing is impractical, as each mutation requires a unique therapeutic strategy. We present a mutation-agnostic, RHO-specific approach using adeno-associated viral vector-mediated homology-independent targeted integration (AAV-HITI). Optimized donor DNA design enables targeted integration and efficient transgene expression from the endogenous RHO locus. In a humanized RP4 mouse model harboring the RHO P23H mutant allele alongside an endogenous wild-type mouse Rho allele, AAV-HITI significantly improves retinal structure, function, and visual acuity up to 1 year post-treatment. Comprehensive molecular analyses characterize on-target editing in mouse retina and off-target editing in a human cell line. These findings establish an effective, human-centric AAV-HITI platform for RP4 and support its evaluation in this and other dominant genetic conditions.",
  "abstract_shown": true,
  "affiliations": [
    "Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy",
    "Institute for Transfusion Medicine and Gene Therapy, Medical Center – University of Freiburg, Freiburg, Germany",
    "Center for Cell and Gene Therapy Freiburg (CGF), Faculty of Medicine, University of Freiburg, Freiburg, Germany",
    "Institute of Medical Bioinformatics and Systems Medicine, Medical Center – University of Freiburg, Freiburg, Germany",
    "German Cancer Consortium (DKTK), Partner site Freiburg, a partnership between DKFZ and Medical Center - University of Freiburg, Freiburg, Germany",
    "Department of Advanced Biomedical Sciences and Department of Translational Medicine, University of Naples “Federico II”, Naples, Italy",
    "Medical Genetics, Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Naples, Italy",
    "Scuola Superiore Meridionale (SSM), Genomics and Experimental Medicine Program, Naples, Italy",
    "Gene Therapy Joint Lab, Department of Advanced Biomedical Sciences and Department of Translational Medicine, University of Naples “Federico II”, Naples, Italy"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Federica Esposito"
    },
    {
      "affs": [
        0
      ],
      "name": "Arjun Padmanabhan"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Manuel Rhiel"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariangela Lupo"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Marrocco"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefano Auricchio"
    },
    {
      "affs": [
        0
      ],
      "name": "Xabier Bujanda Cundin"
    },
    {
      "affs": [
        0
      ],
      "name": "Simona Pellecchia"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Tatjana I. Cornu"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Geoffroy Andrieux"
    },
    {
      "affs": [
        0
      ],
      "name": "Manel Llado-Santaeularia"
    },
    {
      "affs": [
        5
      ],
      "name": "Enrico Maria Surace"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Ivana Trapani"
    },
    {
      "affs": [
        0
      ],
      "name": "Pasqualina Colella"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Gennaro Gambardella"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Toni Cathomen"
    },
    {
      "affs": [
        0,
        6,
        8
      ],
      "name": "Alberto Auricchio"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1cjw2r2hm1t5m.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103047",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710138/",
  "id": "1cjw2r2hm1t5m",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103047",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Retinal Development and Disorders"
    ]
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  "openalex": "W7212245800",
  "pdf_url": null,
  "pmcid": "PMC13710138",
  "pmid": "42727583",
  "published": "2026-09-11",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/1cjw2r2hm1t5m.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:10Z",
      "native_id": "PMC13710138",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103047"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Retinal Development and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Targeted insertion of an optimized donor DNA is effective in a humanized mouse model of dominant retinitis pigmentosa",
  "title_text": "Targeted insertion of an optimized donor DNA is effective in a humanized mouse model of dominant retinitis pigmentosa",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:10Z",
  "url": "https://research.draconitic.com/paper/1cjw2r2hm1t5m",
  "venue": "Cell Reports Medicine",
  "versions": []
}