{
  "abstract": "Autosomal dominant retinitis pigmentosa (adRP) caused by RHO mutations is a leading form of inherited retinal degeneration. Extensive allelic heterogeneity of RHO pathogenic variants limits the translational applicability of mutation-specific gene therapies. To address this, we developed SNARE (SNP-guided Silencing of Aberrant RHO Expression), a mutation-independent, allele-specific antisense oligonucleotide (ASO) strategy. SNARE selectively suppresses mutant RHO transcripts by targeting the common, benign c.-26A/G single-nucleotide polymorphism (SNP) as an allelic discriminator. Candidate gapmer ASOs were screened in engineered reporter lines and validated in patient-derived retinal organoids, identifying RHOligo-A as the lead c.-26A-targeting candidate. In vitro, RHOligo-A achieved robust, preferential knockdown of the target allele, improving RHO localization in retinal organoids, and demonstrated a favorable safety profile with minimal transcriptomic off-target effects and no detectable immunostimulatory activity. Subsequent validation in a novel, humanized RHOP347L/WT mouse model, achieved sustained c.-26A-linked allele-selective suppression, retinal structure preservation, and significantly restored visual function, upon a single intravitreal administration. These findings establish RHOligo-A and SNARE as a scalable, mutation-independent therapeutic platform with strong translational potential and substantial clinical reach for RHO-associated adRP.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 31,
  "authors": [
    {
      "name": "S. Spaag"
    },
    {
      "name": "W.-H. Wu"
    },
    {
      "name": "J. Yun"
    },
    {
      "name": "T. Winogrodzki"
    },
    {
      "name": "A. S. Knudsen"
    },
    {
      "name": "M. Fuso"
    },
    {
      "name": "K. Stingl"
    },
    {
      "name": "G. Komissarov"
    },
    {
      "name": "A. Armento"
    },
    {
      "name": "B. Baumann"
    },
    {
      "name": "L. Kuehlewein"
    },
    {
      "name": "C. Ayuso"
    },
    {
      "name": "L. Fernandez-Caballero"
    },
    {
      "name": "R. Collin"
    },
    {
      "name": "Z. Corradi"
    },
    {
      "name": "S. Roosing"
    },
    {
      "name": "M. Kaltak"
    },
    {
      "name": "C. Lochmann"
    },
    {
      "name": "F. Radboudumc"
    },
    {
      "name": "S. Banfi"
    },
    {
      "name": "M. Karali"
    },
    {
      "name": "S. Bolz"
    },
    {
      "name": "F. Simonelli"
    },
    {
      "name": "K. Dave"
    },
    {
      "name": "S. Kohl"
    },
    {
      "name": "E. Zrenner"
    },
    {
      "name": "A. Demirkol"
    },
    {
      "name": "K. Achberger"
    },
    {
      "name": "B. Wissinger"
    },
    {
      "name": "S. H. Tsang"
    },
    {
      "affs": [
        0
      ],
      "name": "P. De Angeli"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/33g08h9qzdwkb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.25.747013",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.25.747013v1.full",
  "id": "33g08h9qzdwkb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.25.747013v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "1312|Retinal Development and Disorders"
    ]
  ],
  "openalex": "W7204932641",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.25.747013v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/33g08h9qzdwkb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.64898/2026.08.25.747013",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.25.747013v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "A mutation-agnostic and allele-specific ASO strategy demonstrates potent functional rescue and retinal preservation in RHO-linked retinitis pigmentosa",
  "title_text": "A mutation-agnostic and allele-specific ASO strategy demonstrates potent functional rescue and retinal preservation in RHO-linked retinitis pigmentosa",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/33g08h9qzdwkb",
  "venue": "bioRxiv",
  "versions": []
}