Lipid Nanoparticles Consisting of Sterol-Conjugated Ionizable Lipids Enable Prolonged and Safe mRNA Delivery

Jun 18, 2025ACS applied materials & interfaces

Sterol-linked ionizable lipid nanoparticles allow longer and safer mRNA delivery

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Abstract

Five ionizable lipids were selected for optimal LNP formulations at a 40-50% molar ratio.

  • Luciferase mRNA-loaded lipid nanoparticles (LNPs) showed luminescence similar to commercial LNPs made with ALC-0315.
  • These LNPs resulted in prolonged protein expression in mice.
  • Accelerated stability studies indicated that the LNPs had good stability.
  • LNPs carrying varicella-zoster virus (VZV) gE mRNA triggered both humoral and T-cell immune responses.
  • Safety studies suggested that LNPs with these ionizable lipids had improved safety profiles compared to commercially available options.

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