{
  "abstract": "Ribonuclease H1 (RNase H1) cleaves the RNA strand of DNA/RNA heteroduplexes and plays essential roles in R-loop resolution, mitochondrial DNA replication, and antisense oligonucleotide (ASO) activity. Because RNase H1 has also been implicated in ASO-induced cytotoxicity, considerable effort has been focused on minimizing its activation. Here we present a reverse strategy that harnesses RNase H1-mediated cytotoxicity for cancer therapy using an oncogenic microRNA (miR-21) as an intracellular trigger. A designed hairpin DNA/hairpin RNA pair undergoes a hybridization chain reaction to assemble long-nicked DNA/RNA heteroduplexes selectively in miR-21-overexpressing cells. The resulting heteroduplexes induce RNase H1-dependent cytotoxicity in cancer cells while exhibiting minimal effects on normal cells. Treatment also caused redistribution of the paraspeckle protein P54nrb from the nucleoplasm to the nucleoli, consistent with RNase-H1-associated nucleolar stress. Furthermore, lipid-nanoparticle-mediated delivery of the DNA/RNA heterohairpin pair significantly suppressed tumor growth in mice. These findings establish a therapeutic strategy that converts RNase H1, traditionally regarded as a source of oligonucleotide toxicity, into a mechanism for selective anticancer activity through the intracellular assembly of long DNA/RNA heteroduplexes.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Tokyo , , , ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kunihiko Morihiro",
      "orcid": "0000-0002-9642-1031"
    },
    {
      "affs": [
        0
      ],
      "name": "Naoki Harada"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuichiro Koga"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunsong Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Tamako Aiba"
    },
    {
      "affs": [
        0
      ],
      "name": "Akimitsu Okamoto",
      "orcid": "0000-0002-7418-6237"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9f909jkvzsg6w.bib",
  "cited_by": 0,
  "doi": "10.1021/acscentsci.6c01046",
  "fulltext_url": null,
  "id": "9f909jkvzsg6w",
  "issns": [
    "2374-7943",
    "2374-7951"
  ],
  "landing_url": "https://pubs.acs.org/acscii/article/doi/10.1021/acscentsci.6c01046/5449244/Ribonuclease-H1-Hijacking-Oncotherapeutics-through",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7221541664",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acscentsci.6c01046",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/9f909jkvzsg6w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:37Z",
      "native_id": "10.1021/acscentsci.6c01046",
      "source": "crossref",
      "url": "https://pubs.acs.org/acscii/article/doi/10.1021/acscentsci.6c01046/5449244/Ribonuclease-H1-Hijacking-Oncotherapeutics-through"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Interference and Gene Delivery",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Ribonuclease H1 Hijacking: Oncotherapeutics through MicroRNA-Triggered Intracellular Construction of Long DNA/RNA Heteroduplexes",
  "title_text": "Ribonuclease H1 Hijacking: Oncotherapeutics through MicroRNA-Triggered Intracellular Construction of Long DNA/RNA Heteroduplexes",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:37Z",
  "url": "https://research.draconitic.com/paper/9f909jkvzsg6w",
  "venue": "ACS Central Science",
  "versions": []
}