C12-2aN is a crosslinked ionizable lipid developed for mRNA vaccine delivery and dendritic-cell metabolic reprogramming. Its structure combines two piperazine-based ionizable amine cores, a bis-amidine crosslinker, and four hydroxylated C12 hydrophobic tails. When formulated with DOPE, cholesterol, and C14-PEG2000, C12-2aN LNPs enhanced mRNA endosomal escape and activated AMPK–mTORC2-dependent glycolysis, supporting dendritic-cell maturation and antigen presentation. In preclinical mouse studies, C12-2aN LNPs generated robust humoral and cellular immune responses in SARS-CoV-2 RBD and OVA cancer-vaccine models. The formulation also demonstrated reduced liver-associated off-target expression and lower acute inflammatory markers than the tested control formulations. C12-2aN is a preclinical research lipid intended for evaluating metabolically active mRNA vaccine delivery systems.
