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Ugi-reaction-derived ionizable lipids with cyclic tertiary amine heads enable spleen-targeted mRNA delivery
Special ionizable lipids with ring-shaped amine heads help deliver mRNA specifically to the spleen
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Abstract
Twenty-five ionizable lipid molecules were synthesized for nucleic acid delivery, with W19 showing highly selective mRNA delivery to the spleen.
- Lipid nanoparticles (LNPs) are a key platform for delivering nucleic acids.
- Targeting non-hepatic organs with LNPs presents challenges.
- Ionizable lipids were designed to enhance the properties of LNPs for organ-specific delivery.
- The Ugi four-component reaction was utilized to create diverse ionizable lipid structures.
- The synthesized W19 LNPs demonstrated effective mRNA delivery specifically to the spleen after intravenous administration.
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