siRNA lipids
lipids in patisiran
The ionizable cationic lipid such as DODAP has pKa < 7 and can efficiently encapsulate negatively charged nucleic acids at low pH (pH 4) during the ethanol loading procedure.
On mixing the nucleic acids with lipid in ethanol, they form inverted micelle containing nucleic acids surrounded by cationic lipid. If the mixing process was rapid, the inverted micelles will not be aggregated but coated with PEG-lipid, as PEG precipitates at higher polarity to surround the inverted micelles.
After DODAP was developed, DLinDMA was applied in siRNA delivery system for its enhanced potency. Later DLinkC2DMA was further improved and finally arrived at the gold standard lipid DLinMC3DMA (abbreviated to MC3).
The alnylam patisiran that treat polyneuropathy caused by hATTR amyloidosis uses four lipids, DSPC, cholesterol, MC3 and PEG2000-C-DMG.