Carbonate-Bearing Ionizable Lipids for mRNA Delivery to Splenic NK Cells

šŸ„‡ Top 1% JournalJun 11, 2025Journal of the American Chemical Society

Ionizable Lipids with Carbonate Groups for Delivering mRNA to Spleen Natural Killer Cells

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Abstract

CAIL-based lipid nanoparticles achieve robust mRNA translation in splenic NK cells, inducing transfection in 21% of these cells.

  • A library of 161 carbonate-bearing ionizable lipids was designed to enhance mRNA delivery to NK cells.
  • These lipid nanoparticles (LNPs) primarily target the spleen rather than the liver, unlike traditional LNPs.
  • Removing cholesterol from CAIL LNPs significantly improves spleen-targeting specificity and efficacy.
  • Optimized CAIL LNPs may effectively address the challenges of mRNA delivery to NK cells.
  • The findings suggest potential for developing NK cell-based mRNA therapies.

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