Molecular Dynamics‐Guided Sterol Engineering of mRNA‐Lipid Nanoparticles Reprograms Biodistribution and Enhances Spleen‐Selective Immunity
Nine bile-acid-derived sterols varied hydroxylation and alkyl-tail chemistry to probe LNP organization and organ expression. Molecular simulations and experiments linked membrane descriptors with encapsulation and formulation behavior. Replacing cholesterol shifted expression toward the spleen, and a lead sterol enhanced antigen-specific responses. The work offers a preclinical formulation framework rather than validated prediction of human biodistribution.
DOI: 10.1002/advs.76671