D-Lin-MC3-DMA

siRNA-based drugs need a complicated delivery vehicle, that’s because it degraded rapidly in the circulation, difficult to cross the cell membranes and enter the cytoplasm, plus inefficient accumulation in target tissues. The major delivery technology for siRNA is the lipid nanoparticle (LNP) containing ionizable amino lipid, which is the consisted of an ionizable amino lipid (heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate, DLin-MC3-DMA), a phosphatidylcholine (1,2-distearoyl-sn-glycero-3-phosphocholine, DSPC), cholesterol and a coat lipid (polyethylene glycol-dimyristolglycerol, PEG-DMG). As a potent siRNA delivery vehicle, DLin-MC3-DMA is 1000-fold more potent for silencing of a hepatic gene (Factor VII), comparing to its precursor lipid DLin-DMA. The ED50 for LNP containing DLin-MC3-DMA to silence Factor VII was 0.005 mg/kg for mice, and 0.03 mg/kg for TTR in non-human primates.

Reference:

Tam YY, Chen S, Cullis PR. Advances in Lipid Nanoparticles for siRNA Delivery. Pharmaceutics. 2013 Sep 18;5(3):498-507. PMID: 24300520.