Figure 2.

There Is a Strong Relationship between siRNA Metabolites Observed in Liver Homogenate and In Vivo

(A) The graphs on the top compare the metabolites observed in rat liver homogenate to those observed at three increasing in vivo dosing to rats, for both sense and antisense strands. (B) The graphs at the bottom show the correlation between metabolites identified from two different in vivo dose levels in cynos and the metabolites formed after siRNA incubation in cyno liver homogenate. The alignment between in vitro and in vivo observations is strong for the antisense strand. For sense strand, the in vivo samples generally demonstrate further metabolism than in vitro samples. Nevertheless, in both systems, metabolism is largely confined to the triantennary GalNAc moiety.