Figure 3.

Plot of in vivo hepatic gene silencing activity vs. pK_a in mice. The 56 amino lipids were formulated in LNPs and subjected to an ED₅₀ analysis (described in Supporting Information, page 39) and plotted against their pK_a. For 15 lipids the ED₅₀ dose was not achieved, these are indicated by the open diamonds representing the highest dose tested for that lipid. For the remaining lipids (closed diamonds), a polynomial best-fit curve highlights the most active compounds, which exhibit an optimal pK_a between 6.2 and 6.5. Each data point is derived from a four-dose response curve with groups of n=4 mice per dose.