Toward High-Performance mRNA-LNPs through Structural Optimization of Ionizable Lipids
발표자
HO VIET CUONG (한국생명공학연구원)
연구책임자
김윤경 (Korea Research Institute of Bioscience and Biotechnology)
초록
내용
Lipid nanoparticle (LNP)-mediated mRNA delivery has revolutionized vaccination and disease treatment, with the chemical structure of ionizable lipids (ILs) dramatically influencing both efficacy and safety. Here, we report a versatile strategy to enhance protein expression from mRNA delivered by LNPs through structural modifications of ILs, specifically by tuning their head, linker, and tail regions. A library of ILs with systematic variations was synthesized—e.g., incorporating different 5-membered heterocycles in the head group, varying linker functionalities and lengths, and employing either linear or branched tails. LNPs containing each IL variant were evaluated through formulation optimization by measuring their physicochemical properties (e.g., size, PDI, surface charge, and mRNA encapsulation efficiency) and in vivo efficacy screening. Our results clearly demonstrate that the head group structure, linker length, and tail branching significantly affect protein expression levels.