Figure 6. ARO-AAT treatment reduced Z-AAT protein and mRNA in young PiZ mice.

Five-week-old male PiZ mice given 4 subcutaneous injections (Q2W) of 4 mg/kg ARO-AAT, saline, or RNAi-Control and were euthanized 2 weeks after the final injection (n = 9–16). Untreated baseline mice euthanized at 5 weeks of age (n = 15). (A) Plasma was collected at the indicated times and Z-AAT protein measured, shown as the group mean ± SEM relative to pretreatment. (B) Amounts of Z-AAT mRNA in homogenized liver tissue were quantified relative to the geometric mean of the baseline group. (C and D) The amounts of monomeric and polymeric Z-AAT protein in liver lysates of mice at baseline (5 weeks old) or after receiving 4 Q2W injections and then euthanized (13 weeks old) were measured by semiquantitative Western blotting, shown relative to the baseline group as the mean ± SEM. (E) Representative PAS-D–stained liver sections from mice at baseline or injected Q2W with saline, RNAi-Control, or ARO-AAT. Globule number, globule size, and the area of the liver containing globules were measured by a densitometric method (F, G, and H). Comparisons between groups in panels B–D and F–H were performed using nonparametric Wilcoxon’s rank sum test.