Optimized Lipid Nanoparticles with Tail‐Modified Ionizable Lipids for Safer mRNA Delivery
A library of 56 ionizable lipids combined biodegradable disulfide linkages with different hydrophobic tail lengths and branching patterns. Structure-activity testing linked tail architecture to endosomal escape, translation, and biocompatibility. Optimized particles reduced cytotoxicity and cytokine induction, with immune-response evaluation extending to a nonhuman primate model. These findings support lipid design, rather than establishing human safety.
DOI: 10.1002/advs.76539