C12-4 (Lipid A-4)

C12-4 (C12-494, Lipid A-4) is a branched-chain ionizable cationic lipidoid that has been used in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA. LNPs containing lipid A4 and encapsulating an mRNA reporter accumulate in the uterus, placenta, and ovaries, as well as to the spleen and liver, in pregnant mouse dams unlike LNPs containing the branched-chain ionizable cationic lipidoid C12-200, which primarily accumulate in the liver. Intravenous administration of LNPs containing lipid A4 and encapsulating mRNA encoding VEGF increase placental VEGFR1 levels and mean fetal blood vessel area without inducing liver damage in pregnant mouse dams.