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. 2016 Jan 15;4(1):e00207. doi: 10.1002/prp2.207

Figure 6.

Figure 6

Effects of increasing doses of the fX and fIX lipid nanoparticle (LNP) on mRNA expression, measurement of activated partial thromboplastin time (aPTT) and prothrombin time (PT), clot weight, and bleeding. (A) mRNA expression was calculated relative to vehicle control. Individual animals and group means ± SEM are shown. Animals were dosed with a single dose and sacrificed at day 7 (post efficacy/bleeding study) for determination of hepatic fX and fIX mRNA levels. (B) fX siRNA‐dependent increase in aPTT and PT (top panel). fIX siRNA dose‐dependently increased aPTT but did not affect PT. (C) Effects of fX siRNA (upper panel) and fIX siRNA (lower panel), on CW and CBT showing that intermediate doses of fIX siRNA exist that provide significant inhibition of thrombosis at no cost on bleeding. (D) Separation of efficacy curve for fX and fIX siRNA for similar prolongation of CBT. *P < 0.05, **P < 0.01, ***P < 0.0001 versus 0 (control). FIX–0.003, fIX siRNA‐51797 dosed at 0.003 mg/kg. FIX–0.01, fIX siRNA‐51797 dosed at 0.01 mg/kg. FIX–0.03, fIX siRNA‐51797 dosed at 0.03 mg/kg. FIX–0.1, fIX siRNA‐51797 dosed at 0.1 mg/kg. FIX–0.3, fIX siRNA‐51797 dosed at 0.3 mg/kg. FIX–0.6, fIX siRNA‐51797 dosed at 0.6 mg/kg. FX–0.01, fX siRNA‐53334 dosed at 0.01 mg/kg. FX–0.03, fX siRNA‐53334 dosed at 0.03 mg/kg. FX–0.1, fX siRNA‐53334 dosed at 0.1 mg/kg. FX–0.3, fX siRNA‐53334 dosed at 0.3 mg/kg. FX–1, fX siRNA‐53334 dosed at 1 mg/kg. nt, nontargeting.