{
  "abstract": "Selectively eliminating cancer cells based on their oncogenic drivers holds great promise but remains challenging for targeted cancer therapy. Here, we present ORCA (Oncogenic RNA-triggered Cancer Ablation), a programmable and modular platform that couples RADAR-based detection of oncogenic RNA with conditional expression of therapeutic payloads in cancer cells. We identify RADAR sensors targeting the transcripts of endogenously amplified oncogenes, including MYC, FGFR2 and wild-type KRAS in colorectal and gastric cancer cells. Focusing on colorectal cancer (CRC) driven by extrachromosomal DNA-amplified MYC, we demonstrate targeted ablation of high-MYC cancer cells using two orthogonal strategies: anti-CD19 CAR-T therapy and enzyme-prodrug therapy. In vivo delivery of ORCA using adeno-associated virus (AAV) suppresses tumor growth in a subcutaneous xenograft model and prolongs survival in a CRC liver metastasis model. ORCA establishes oncogenic RNAs as actionable inputs for targeted cancer therapy via programmable RNA sensing, thus offering a strategy to target tumors through the transcripts of otherwise difficult-to-drug oncogenes such as MYC.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "M. Zhang"
    },
    {
      "name": "Y. Hu"
    },
    {
      "name": "S. A. Yamada-Hunter"
    },
    {
      "name": "E. Sotillo"
    },
    {
      "name": "H. Dai"
    },
    {
      "name": "C. C. Call"
    },
    {
      "name": "A. M. Tousley"
    },
    {
      "name": "S. J. Kim"
    },
    {
      "name": "W. Liu"
    },
    {
      "name": "M. M. Winslow"
    },
    {
      "name": "C. Mackall"
    },
    {
      "affs": [
        0
      ],
      "name": "X. J. Gao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2nj1akqt846c2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.02.763782",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763782v1.full",
  "id": "2nj1akqt846c2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763782v1",
  "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",
      "synthetic biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763782v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2nj1akqt846c2.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:03Z",
      "native_id": "10.64898/2026.11.02.763782",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.02.763782v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:synthetic biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Targeted cancer ablation via programmable sensing of amplified oncogenic RNA",
  "title_text": "Targeted cancer ablation via programmable sensing of amplified oncogenic RNA",
  "type": "preprint",
  "updated_at": "2026-11-05T00:21:17Z",
  "url": "https://research.draconitic.com/paper/2nj1akqt846c2",
  "venue": "bioRxiv",
  "versions": []
}