fig10

Figure 10. A: RNAi encapsulated in LNPs are protected from the actions of nucleases and targeted to the liver. LNPs are specifically targeted to the liver because they bind apolipoproteins E in the blood circulation and then bind to the ApoE-LDL receptor on the surface of the hepatocytes. B: LNP decorated with Apo E bind to Apo E receptor on the hepatocyte plasma membrane. C: DLin-MC3-DMA lipids at the LNP surface are neutral at pH 7. Inside the endosome, DLin-MC3-DMA becomes cationic, which favors either fusion with the endosome membrane and siRNA release or endosome breakage caused by the “proton pump” osmotic effect.