Effect of fVII, fXI, fXII, and HK ASOs on hepatic mRNA expression, protein levels, and activity. Male New Zealand white rabbits were treated subcutaneously with control, fVII, fXI, fXII, and HK ASO for 4 weeks at 15-mg/kg twice-weekly dose (n = 8 per treatment group). Two days after final dosing, blood was collected for quantification of (A) hepatic fVII, fXI, fXII, and HK mRNA expression, (B) fXI, fXII, and HK protein levels by immunoblot analysis, and (C) procoagulant activity in fVII- (black bars), fXI- (dark gray bars), fXII- (light gray bars), and HK-deficient (white bars) human plasma. The bars for mRNA and activity levels represent the mean of 3 separate experiments for each rabbit, whereas the lines above the bars reflect the SD. *P < .05 compared with control ASO.