596958 Disclosed herein is a cationic lipid of formula I (DLin-M-C3-DMA, MC3 or M-C3), an improved lipid formulation comprising a cationic lipid of formula I 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. In one embodiment the lipid formulation comprises 30–65% of a cationic lipid of formula I, 5–10% of a neutral lipid, 25–40% of a sterol and 0.5–0% of a polyethyle glycol (PEG) or PEG-modified lipid.