{
  "abstract": "Lipid nanoparticles (LNPs) are the leading delivery vehicles for mRNA therapeutics, yet transient expression and limited formulation stability constrain their broader therapeutic application. Here we report the phenotype-driven discovery of an ionizable lipid (HI-62) bearing a 1,3,5-triazinane-2-thione (cyclic-thiourea) headgroup that reproducibly assemble mRNA into onion-like multilamellar nanoparticles. Cryogenic electron microscopy revealed ordered internal lamellae, while molecular-dynamics simulations supported a cooperative assembly model involving pH-responsive electrostatics, headgroup preorganization and short-range directional interactions. The lead HI-62 formulation maintained greater than 95% mRNA encapsulation across N/P ratios of 3-7, prolonged reporter expression for substantially longer durations than benchmark formulations following intravenous and intramuscular delivery, and retains physicochemical integrity and in vivo potency after repeated freeze-thaw cycles and 18 months of storage at -20. In the tumor models, HI-62 elicits robust cellular responses and achieved significant inhibition of tumor growth. These findings establish cyclic-thiourea headgroup chemistry as a design principle for programming lipid-RNA organization into multilamellar architecture, and provide a design principle for next-generation LNPs platform with durable protein expression and superior stability. The HI-62-based formulation has been utilized in mRNA cancer vaccine program which will enter clinical development in months.",
  "abstract_shown": true,
  "affiliations": [
    "EnCureGen Pharmaceuticals Co., Ltd. ; State Key Laboratory of Respiratory Disease, Guangzhou Medical University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. Hui"
    },
    {
      "name": "R. Cai"
    },
    {
      "name": "L. Zhang"
    },
    {
      "name": "Z. Huang"
    },
    {
      "name": "H. Gu"
    },
    {
      "name": "N. Zheng"
    },
    {
      "name": "C. Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9kfn5kza4ydz4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.07.749752",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749752v1.full",
  "id": "9kfn5kza4ydz4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749752v1",
  "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",
      "bioengineering"
    ],
    [
      "openalex",
      "1312|RNA Interference and Gene Delivery"
    ]
  ],
  "openalex": "W7212186424",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749752v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9kfn5kza4ydz4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:42Z",
      "native_id": "10.64898/2026.09.07.749752",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749752v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Cyclic-thiourea ionizable lipids program multilamellar mRNA-LNPs for sustained expression, frozen-storage stability and potent vaccine immunotherapy",
  "title_text": "Cyclic-thiourea ionizable lipids program multilamellar mRNA-LNPs for sustained expression, frozen-storage stability and potent vaccine immunotherapy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:42Z",
  "url": "https://research.draconitic.com/paper/9kfn5kza4ydz4",
  "venue": "bioRxiv",
  "versions": []
}