Figure 5.

A Significant Correlation Is Observed between the In Vitro Stability of siRNAs in Mouse Liver Homogenate and Their In Vivo PD Efficacy

This plot demonstrates the antisense strand stability after 72 h of incubation in a mouse liver homogenate versus the target knockdown efficacy for various siRNAs. These two variables show a significant correlation to one another (p < 0.0001). Although the absolute correlation is modest (Pearson r: –0.54), the tremendous value of liver stability assay for decision making cannot be overlooked. Most siRNAs with in vitro stability values greater than 50% show target knockdown after in vivo administration to mice (data points in the upper left quadrant). In contrast, the majority of siRNA constructs with less than 50% in vitro stability of antisense strand do not show any knockdown when dosed to animals (data points at the lower right quadrant). It should be noted that a few siRNAs generated stability values significantly greater than 100% in this assay, which was distinctively characterized as experimental failure. Therefore, 7 data points with siRNA stability larger than 120% were excluded from further analysis and they are not shown in this plot.