Nature子刊：宫宁强等开发新型LNP，重编程树突状细胞代谢，增强mRNA疫苗效力

Core Viewpoint - The research highlights a novel approach to enhance mRNA vaccine efficacy by reprogramming dendritic cell metabolism using crosslinked ionizable lipids, specifically C12-2aN, which opens new avenues for the development of next-generation mRNA-LNPs [4][5][9]. Group 1: Research Findings - The study developed a crosslinked ionizable lipid, C12-2aN, which possesses intrinsic metabolic regulatory properties, enhancing mRNA vaccine effectiveness through metabolic reprogramming of dendritic cells [5][7]. - C12-2aN LNPs demonstrated superior vaccine efficacy in SARS-CoV-2 and OVA tumor models, showing stronger neutralization capacity against pseudovirus infections and significantly improved survival rates compared to control LNPs without crosslinking [7][9]. - The C12-2aN LNPs outperformed FDA-approved LNPs in reducing off-target delivery and minimizing immunogenicity, indicating a significant advancement in mRNA vaccine safety and effectiveness [9]. Group 2: Methodology - The research utilized imidoester-based coupling chemistry to design the crosslinked ionizable lipid, which not only serves as an mRNA carrier but also acts as a metabolic regulator by activating the mTORC2 pathway to stimulate glycolysis [7]. - The innovative chemical design of the new LNP allows for an "active" enhancement of immune responses by modulating the metabolic state of dendritic cells, marking a significant step forward in mRNA vaccine technology [9].