Ionizable Cholesterol Analogs as the Fifth Component of Lipid Nanoparticles for Selective Targeting Delivery of mRNA

A spleen-targeted formulation achieved 95% delivery efficiency for mRNA in lipid nanoparticles.

• Targeting delivery of mRNA to specific organs is crucial for effective therapies with fewer side effects.
• Current lipid nanoparticle formulations face challenges in delivering mRNA beyond the liver.
• The addition of ionizable cholesterol analogs allows for selective targeting by modifying the composition of lipid nanoparticles.
• A formulation targeting the spleen reached a delivery efficiency of 95%, while the lung-targeted version achieved 78%.
• Using a self-developed ionizable lipid, targeting efficiencies for the spleen and lungs were 96% and 71%, respectively.
• The stability and safety of lipid nanoparticles were maintained, with no increase in toxicity observed following the incorporation of the fifth component.

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