Core Viewpoint - The research highlights the critical role of the three-dimensional spatial conformation of ionizable lipids in the effective delivery of mRNA, showcasing the potential of AI-driven strategies in optimizing organ-specific targeting of lipid nanoparticles (LNPs) for mRNA therapeutics [4][18]. Group 1: Research Findings - An AI model was developed to analyze the three-dimensional spatial conformation of ionizable lipids, leading to the identification of lipid P1, which exhibits a stable three-tailed conical structure that enhances mRNA delivery targeting the spleen [4][6]. - The mRNA vaccine delivered via P1-based LNPs triggered strong antibody and T cell responses in mouse tumor models, significantly inhibiting tumor growth [4][16]. - The study emphasizes that the spatial conformation of lipids is crucial for organ targeting, with the conical structure of P1 facilitating efficient mRNA loading, endosomal escape, and the formation of a protein corona that directs LNPs to immune cells in the spleen [11][12][18]. Group 2: Mechanism and Implications - The research transitioned the design of ionizable lipids from a trial-and-error approach to a rational design based on three-dimensional spatial conformation, inducing strong immune responses and achieving significant tumor suppression in melanoma and colon cancer models [18][19]. - The AI framework developed in this study can be applied to the design of delivery systems for other nucleic acid drugs, such as siRNA and DNA vaccines, paving the way for personalized medicine tailored to specific patient needs [19].