Figure 6.

In Vivo Expression and Kinetics of HdaPCSK9

(A and B) Quantitative ELISA analysis for MdaPCSK9 following single intramuscular injection of DMAb plasmids in (A) B6.Cg-foxn1nu/J nude mice and (B) C57BL/6J wild-type mice. Quantitative ELISAs were performed for anti-hPCSK9 DMAb at the indicated time points. Plates were coated with anti-human Fc antibody, followed by incubation with anti-human IgG-HRP antibody for the detection of HdaPCSK9. Values represent mean expression in each group (n = 5) ± SEM. (C) Binding western blot analysis of HdaPCSK9 from mouse sera. Anti-PCSK9 DMAbs obtained from mouse sera at 5 days post-treatment were evaluated for binding against recombinant mouse and human PCSK9 proteins. (D) Histology and immunohistochemistry of HdaPCSK9 in mouse muscle (magnification, 20×; scale bars, 100 μm). Immunohistochemistry of PCSK9 using anti-human IgG-HRP for mouse muscle sections at day 5 in C57BL/6J wild-type is shown. Insets show 30% magnification of the images. Prominent browning is detected in HdaPCSK9-treated muscle. H&E-stained sections of treated muscle show no observable tissue damage. The images were taken from the muscle mid-section, away from the needle tract area.