{
  "abstract": "Extracellular microRNAs (miRNAs) contribute to metastasis through communication between tumour cells and their microenvironment, yet their sustained, sequence-selective depletion remains challenging. Here we report Programmable RNA-Intercepting Molecular Eraser (PRIME), a membrane-anchored DNA nanomachine that organizes miRNA recognition and catalytic degradation at the cell surface. A double-tetrahedral DNA scaffold positions a programmable recognition hairpin beside RNase H. Target binding generates an RNA/DNA hybrid for RNase H-mediated cleavage, and product release resets the hairpin for subsequent degradation cycles. Membrane-anchored PRIME depleted matched extracellular miRNAs by 70.6-89.4% across lung, breast and cervical cancer cell models. Multi-target PRIME (M-PRIME) inhibited migration by 71.3-96.0% in Transwell assays across these models. To evaluate its therapeutic potential, we established an orthotopic lung-tumour model and an early-intervention breast-cancer lung-colonization model in mice. Aptamer-directed M-PRIME combined with gemcitabine reduced pulmonary tumour burden by 74.5% in established lung tumours and 93.2% in the lung-colonization model. These effects were consistent with PRIME-mediated extracellular miRNA degradation, with circulating target miRNA levels reduced by 77.5-98.7% relative to gemcitabine alone. Together, these findings establish a programmable material strategy for sustained extracellular RNA depletion and support its potential to enhance chemotherapy in preclinical tumour models.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Organic-Inorganic Composites, Beijing Key Laboratory of Bioprocess, Beijing Advanced Innovation Center for Soft Matter Science and Engin"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Z. Zhou"
    },
    {
      "name": "L. Zhang"
    },
    {
      "name": "X. Wang"
    },
    {
      "name": "C. Zhang"
    },
    {
      "name": "Q. Yan"
    },
    {
      "name": "S. Wang"
    },
    {
      "name": "H. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "X. Su"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/294wbc3ttcsbg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.30.755580",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755580v1.full",
  "id": "294wbc3ttcsbg",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755580v1",
  "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",
      "1312|Advanced biosensing and bioanalysis techniques"
    ]
  ],
  "openalex": "W7215073153",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755580v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/294wbc3ttcsbg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:35Z",
      "native_id": "10.64898/2026.09.30.755580",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755580v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Advanced biosensing and bioanalysis techniques",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Sequence-specific and programmable catalytic degradation of extracellular microRNAs by membrane-anchored DNA nanomachines",
  "title_text": "Sequence-specific and programmable catalytic degradation of extracellular microRNAs by membrane-anchored DNA nanomachines",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:35Z",
  "url": "https://research.draconitic.com/paper/294wbc3ttcsbg",
  "venue": "bioRxiv",
  "versions": []
}