{
  "abstract": "Extending oligonucleotide therapeutics beyond the liver remains a central challenge for RNA medicine. Here, we describe a lipid-conjugated oligonucleotide (LiCO), a benzimidazole-enabled lipid-duplex RNA conjugate platform synthesized as a single chemical entity by standard solid-phase chemistry. Structure-activity screening identified a 5′-passenger-strand hexadecyl (C16) conjugate whose benzimidazole (SDL) linker markedly improved delivery activity relative to a linker-free analog, and studies in CD36-knockout mice established CD36-dependent uptake as the principal driver of extrahepatic tropism. A single systemic dose in mice produced >90% target knockdown in skeletal muscle, heart, aorta, and adipose tissue, with ≥50% silencing persisting for 6 months and measurable activity at 9 months, whereas hepatic silencing was transient. In cynomolgus macaques, two intravenous doses of LiCO-siMSTN achieved ∼90% myostatin mRNA knockdown, 60%–70% suppression of circulating myostatin protein through day 98, and progressive muscle hypertrophy without adverse clinical, hematological, or biochemical findings. In situ hybridization confirmed deep penetration of myofibers, myocardium, and aortic smooth muscle. LiCO also enabled potent local delivery to the synovium, retina, and bladder with minimal systemic exposure. LiCO offers a scalable, versatile platform for neuromuscular, metabolic, and localized disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Ractigen Therapeutics, Nantong, Jiangsu, China",
    "Ractigen Therapeutics, Nantong, Jiangsu, China; Corresponding author: Long-Cheng Li, Ractigen Therapeutics, 4th floor, Bldg.1, BioBay 3B, Suzhou Industrial Park, 99 Jingu Rd, Suzhou, Jiangsu Province 215000, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Moorim Kang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zubao Gan"
    },
    {
      "affs": [
        0
      ],
      "name": "Qifeng Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei-Hsiang Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Jie Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Feifei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaojie Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Ke Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Vera Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Long-Cheng Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/23yqk1d06xsyf.bib",
  "cited_by": 0,
  "doi": "10.1016/j.omtn.2026.103154",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2162253126003252",
  "id": "23yqk1d06xsyf",
  "issns": [
    "2162-2531"
  ],
  "landing_url": "https://doi.org/10.1016/j.omtn.2026.103154",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RM1-950"
    ],
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7223157034",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/23yqk1d06xsyf.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T14:21:05Z",
      "native_id": "044ffd84368549bcaf941610e73d249f",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.omtn.2026.103154"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Interference and Gene Delivery",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The LiCO platform: A novel benzimidazole-based lipid conjugate for versatile and sustained siRNA delivery beyond the liver",
  "title_text": "The LiCO platform: A novel benzimidazole-based lipid conjugate for versatile and sustained siRNA delivery beyond the liver",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T14:20:18Z",
  "url": "https://research.draconitic.com/paper/23yqk1d06xsyf",
  "venue": "Molecular Therapy: Nucleic Acids",
  "versions": []
}