Disclosed herein is a compound of formula I (DLin-M-C3-DMA, MC3 or M-C3), an improved lipid formulation comprising the compound and corresponding methods of use. Also disclosed are targeting lipids, such as an N-acetyl galactosamine comprising lipid, and specific lipid formulations comprising such targeting lipids. Also disclosed is a nucleic acid-lipid particle comprising a compound of formula I, a neutral lipid, a sterol a polyethyle glycol (PEG) or PEG-modified lipid, and a therapeutic siRNA encapsulated in the lipid particle. In one embodiment the nucleic acid-lipid particle has a size ranging from 70 to 200 nm.
