Fig. 4.

Silencing of human PCSK9 mRNA and protein reduction in PCSK9 humanized mice. (A) Transgenic mice (n = 4 per group) expressing the human PCSK9 full-length cDNA under the apoE promoter were dosed with LNP-PCS-A2 and LNP-PCS-C2, and LNP-Crtl or PBS. Both LNP-PCS-C2 and LNP-PCS-A2 significantly lowered the human transcript as measured by quantitative PCR 3 days after dose. Each value is the group mean ± STDEV. (One-way ANOVA, Student's t test, P ≤ 0.001 between PBS- and PCSK9 siRNA-treated groups). (B) Circulating human PCSK9 protein levels were reduced in treated vs. control transgenic mice (n = 4 per group) as measured by ELISA. Each value represents group mean ± STDEV. All time points for the PCSK9 siRNA treated groups are statistically significant compared with PBS (Two-way ANOVA, Bonferroni test, P ≤ 0.01).