Figure 5
From: Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human Factor VIII
Time course of targeted human BDD-F8 transgene expression and FVIII activity. F8KO mice were injected without (Veh) or with AAV8-SaCas9-sg1 plus AAV8-BDD-F8 vectors, at a 1:5 ratio and a total AAV dose of 6 × 1011 vg/kg. Liver tissue was harvested and plasma collected from mice at the indicated time points after injection. (A,B) Viral infectivity in the liver, as indicated by AAV8-SaCas9-sg1 (A) and AAV8-BDD-F8 (B) viral genome copies, measured by real-time quantitative PCR. (C,D) Relative mRNA levels of SaCas9 (C) and hybrid Alb/BDD-F8 (D) in liver cells, measured by real-time RT-PCR. Plasma FVIII protein level (D) and activity (E), assessed by FVIII ELISA and Chromogenix activity assay, respectively. Data are means ± SE; n = 3–5 mice in all groups except for the Vehicle group, which had n = 12. In this control group, data were pooled from all time points (0.5–7 months) in all vehicle-injected F8KO mice.
