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

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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