{
  "id": 6533279,
  "title": "Cyclic-thiourea ionizable lipids program multilamellar mRNA-LNPs for sustained expression, frozen-storage stability and potent vaccine immunotherapy",
  "url": "https://urgent.news/2026/09/09/cyclic-thiourea-ionizable-lipids-program-multilamellar-mrna-lnps-for",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-09T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749752v1?rss=1"
  },
  "original_language": "en",
  "account": "Lipid nanoparticles (LNPs) have become essential for mRNA therapeutics delivery; however, their transient expression and unstable formulation limit their wider use. Scientists have now discovered a lipid nanoparticle (HI-62) that has ionizable properties, featuring a 1,3,5-triazinane-2-thione headgroup. This new design allows for consistent assembly of mRNA into onion-like multilamellar nanoparticles.\n\nCryo-electron microscopy showed the ordered internal lamellae structure, while molecular dynamics simulations supported a cooperative assembly model driven by pH-responsive electrostatics, headgroup preorganization, and short-range directional interactions. The HI-62 formulation can maintain over 95% mRNA encapsulation, ranging from N/P ratios of 3-7. This enhances reporter expression duration significantly compared to existing formulations following intravenous or intramuscular delivery.\n\nThe stability of the HI-62 formulation is also remarkable, as it retains its physicochemical integrity and in vivo potency even after repeated freeze-thaw cycles and 18 months of storage at -20°C. In tumor models, this new LNP formulation elicits robust cellular responses and demonstrates considerable inhibition of tumor growth. This discovery establishes cyclic-thiourea headgroup chemistry as a design principle for programming lipid-RNA organization into multilamellar architecture, providing a foundation for developing next-generation LNPs with durable protein expression and superior stability.\n\nThe HI-62-based LNP formulation is currently being used in an mRNA cancer vaccine program, which is expected to enter clinical development in the coming months.",
  "summary": "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…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}