DLin-MC3-DMA

DLin-MC3-DMA, commonly referred to as MC3, is one of the most widely used reference ionizable lipids and remains a key benchmark for evaluating the performance of new ionizable lipid candidates. Its structure consists of two linoleyl chains connected through a central carbon bearing a 4-(dimethylamino)butanoate ester group. This design provides an apparent pKa within the range associated with efficient nucleic acid encapsulation during LNP formulation and effective endosomal release following cellular uptake.

MC3 is the ionizable lipid used in patisiran (Onpattro), the first approved siRNA therapeutic, and it remains one of the most widely used reference lipids in both siRNA and mRNA delivery research. It is commonly employed as a positive control and comparator in applications including siRNA–LNP formulation optimization, hepatic delivery studies, and performance benchmarking of newly developed ionizable lipids.

Due to the presence of polyunsaturated linoleyl chains, MC3 is more susceptible to oxidation compared with lipids containing saturated tails. Improper storage or handling conditions may lead to oxidation and reduced performance before the lipid is incorporated into an LNP formulation. To maintain product quality, MC3 is packaged under an argon atmosphere and supplied confirmed free of N-oxide impurities.