Fig. 2. The helper lipid DOTAP improves specificity for the pancreas by decreasing off-target protein expression.
LNPs containing mLuc were formulated using each of three different lipidoids—(A) 306Oi10, (B) 200Oi10, or (C) 514O6,10—in a molar ratio of 35% lipidoid/40% helper lipid/22.5% cholesterol/2.5% PEG-lipid and administered to C57BL/6 mice (mRNA at a dose of 0.5 mg/kg) (n = 3 mice per group). Three hours later, mice were injected with d-luciferin, euthanized, and dissected for ex vivo luminescence imaging using IVIS. The left panels depict representative IVIS images of key organs, the middle panels quantify mLuc expression, the right panels illustrate the percentage of protein expression occurring in the pancreas. Error bars represent SEM. Analysis of variance (ANOVA) with post hoc Tukey-Kramer was used to compare the fraction of total signal that occurred within the pancreas across helper lipids. **P < 0.01 and ***P < 0.005.