Platelets are anucleate cells that play essential roles in hemostasis, thrombosis, and immune regulation. Despite growing interest in platelet-based therapeutics, genetic manipulation of platelets remains highly limited due to their extreme sensitivity to external stimuli. In this study, the ionizable lipid SNU3 developed for higher efficiency with minimal platelet activation and delivered mRNA at than with the commercial ionizable lipid.
SNU3 formulation was optimized by adjusting various helper lipids and PEG-lipid ratios using nanoluciferase as a reporter gene. To evaluate therapeutic protein production in platelets, human erythropoietin mRNA was encapsulated in SNU3 lipid nanoparticles (LNPs). SNU3 LNPs exhibited a threefold higher expression level compared with a commercial ionizable lipid (ALC-0315). These results demonstrate the potential of the SNU3 ionizable lipid for therapeutic protein expression in platelets and highlight its promise for platelet-targeted gene delivery.