Injection site-retained lipid nanoparticles for targeted intramuscular delivery of mRNA RSV prefusion-F vaccine

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transfection and cytotoxicity assays revealed that LNPs formulated with YK-201, YK-202, and YK-209 showed superior transfection efficiency and low cytotoxicity. In a mouse model, intramuscular injection of Fluc mRNA-LNPs resulted in sustained and localized protein expression at the injection site. When applied to prepare RSV preF-mRNA vaccines, these novel LNPs elicited robust humoral immune responses and reduced lung damage, outperforming the clinically used SM-102. The safety of the LNP formulations was subsequently demonstrated in a mouse model. Collectively, these findings highlight the potential of these novel ionizable lipids as effective injection site-retained mRNA vaccine delivery vehicles.