Effect of FXI ASO treatment on hepatic FXI mRNA levels, FXI enzymatic activity, and aPTT ratio in mice. FXI ASO activity was initially characterized in normal mice by measuring the effect of FXI ASO treatment on hepatic FXI mRNA levels and plasma FXI activity levels. Because FXI has a relatively long half-life (∼ 52 hours in human plasma), a multidose regimen with doses ranging from 5 to 50 mg/kg was initially used. Male BALB/c mice were treated subcutaneously with FXI ASO twice weekly for 3 weeks at indicated doses (n = 4 per dosing group). Three days after final dosing, we measured (A) hepatic mRNA levels of FXI as well as nontargeted coagulation factors by RPA, (B) FXI plasma protein levels, (C) FXI enzymatic activity levels, and (D-E) aPTT and PT ratios. Onset and duration of hepatic FXI mRNA reduction and corresponding anticoagulation in mice in response to a single injection of FXI ASO (50 mg/kg). *P ≤ .05 compared with untreated control.