{
  "abstract": "Targeting GC-rich gene loci is a major challenge owing to their high duplex stability, repetitive sequence composition, and propensity to adopt alternative DNA structures. Triplex-forming oligonucleotides (TFOs) provide a programmable strategy toward the recognition of GC-rich DNA, but their application is restricted by the limited recognition capabilities of natural nucleobases in a cellular setting. Here, we overcome this barrier using parallel-binding TFOs containing the synthetic nucleobase 6-amino-5-nitropyridin-2-one (Z), which enables pH-independent recognition of G-C base pairs. Using two structurally distinct regulatory elements within the MYC promoter, we show that Z-modified TFOs form stable, sequence-selective triplexes that repress promoter activity by 50%–80% in both episomal reporter assays and at endogenous gene loci. Notably, the greatest repression was observed at a GC-rich quadruplex-forming element that functions as a structural hub for transcription factor recruitment. To our knowledge, this represents the first demonstration that a simple nucleobase modification alone is sufficient to enable parallel-binding TFOs to repress expression of an endogenous gene, establishing a general strategy for targeting GC-rich regulatory elements through programmable DNA recognition.",
  "abstract_shown": true,
  "affiliations": [
    "School of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth , Portsmouth PO1 2DT ,",
    "Foundation for Applied Molecular Evolution , Alachua, FL 32615 ,",
    "Firebird Biomolecular Sciences LLC , Alachua, FL 32615 ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ruolin Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael Brazzill"
    },
    {
      "affs": [
        0
      ],
      "name": "Dylan Justice"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicholas Buckham"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Cen Chen",
      "orcid": "0000-0002-6883-9369"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Shuichi Hoshika"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Steven A Benner"
    },
    {
      "affs": [
        0
      ],
      "name": "David A Rusling",
      "orcid": "0000-0002-7442-686X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fd9s19f12dsda.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag998",
  "fulltext_url": "https://europepmc.org/articles/PMC13696076",
  "id": "fd9s19f12dsda",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag998/8986556",
  "language": "eng",
  "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|DNA and Nucleic Acid Chemistry"
    ]
  ],
  "openalex": "W7223570630",
  "pdf_url": "https://academic.oup.com/nar/article-pdf/54/19/gkag998/72410586/gkag998.pdf",
  "pmcid": "PMC13696076",
  "pmid": "42927771",
  "published": "2026-10-01",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/fd9s19f12dsda.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:50Z",
      "native_id": "10.1093/nar/gkag998",
      "source": "crossref",
      "url": "https://academic.oup.com/nar/article/doi/10.1093/nar/gkag998/8986556"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42927771",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42927771"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA and Nucleic Acid Chemistry",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Sequence-specific targeting of GC-rich gene loci by parallel triplex-forming oligonucleotides containing a modified nucleobase",
  "title_text": "Sequence-specific targeting of GC-rich gene loci by parallel triplex-forming oligonucleotides containing a modified nucleobase",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/fd9s19f12dsda",
  "venue": "Nucleic Acids Research",
  "versions": []
}