{
  "abstract": "Although direct RNA degradation offers an alternative to occupancy-driven activity, it has relied on complex natural product-derived cleavage modules such as bleomycin. Here, we show that a compact synthetic Fe(II)-coordinating warhead can be programmed for selective RNA degradation in cells. Coupling this cleavage module to a small molecule that recognizes expanded r(CUG) repeats that cause myotonic dystrophy type 1 (DM1) afforded selective degradation of the pathogenic RNA while sparing wild type and transcripts harboring short r(CUG) repeats. In DM1 patient-derived myoblasts, degradation of mutant repeat RNA reduced DM1-associated pathology including formation of nuclear foci, sequestration of MBNL1, and alternative pre-mRNA splicing defects, without inducing DNA damage. These studies establish that minimal synthetic cleavage modules can replace complex natural product warheads to enable selective degradation of disease-causing RNAs in cells.",
  "abstract_shown": true,
  "affiliations": [
    "Scripps Florida"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "J. Shan"
    },
    {
      "name": "S. Kovachka"
    },
    {
      "name": "K. Sung"
    },
    {
      "affs": [
        0
      ],
      "name": "M. D. Disney"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2ndhjyaar86d6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.764312",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764312v1.full",
  "id": "2ndhjyaar86d6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764312v1",
  "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",
      "biochemistry"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764312v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2ndhjyaar86d6.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:02Z",
      "native_id": "10.64898/2026.11.04.764312",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764312v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "A Minimal Synthetic Cleavage Module Enables Selective Degradation of Pathogenic r(CUG) Repeats in Cells",
  "title_text": "A Minimal Synthetic Cleavage Module Enables Selective Degradation of Pathogenic r(CUG) Repeats in Cells",
  "type": "preprint",
  "updated_at": "2026-11-07T00:21:10Z",
  "url": "https://research.draconitic.com/paper/2ndhjyaar86d6",
  "venue": "bioRxiv",
  "versions": []
}