Cationic Lipids

The molecular architecture of cationic lipids used as nucleic acid carriers is similar to that of natural lipids, with the major difference being their cationic head group, so cationic lipids have the ability to form aggregate complexes with anionic nucleic acids such as DNA or RNA. Advantages of cationic lipid-mediated transfection include high efficiency, ability to transfect a wide range of cell types, reproducibility, and simplicity.

Ionizable cationic lipids (including DOTMA, DODAP, DLin-KC2-DMA, and D-Lin-MC3-DMA) are pH sensitive and highly effective for in vivo transfection. These ionizable cationic lipids are positively charged at low pH (the ability to complex nucleic acids), but mostly uncharged at the pH of blood (pH 7.4) (slow elimination and good tolerability). The ionizable cationic lipids shape and acid-dissociation constant optimization dramatically improved lipid nanoparticles (LNPs) potency, thereby enabling clinical translation.