Fig. 3.

Base editor-mediated in vivo knock-out of human PCSK9 and mouse Pcsk9 in hPCSK9-KI mice. a Targeted regions at human PCSK9 and mouse Pcsk9 loci. The gMH guide RNA has perfect complementarity to the mouse Pcsk9 locus and a single nucleotide mismatch to the human gene (A vs G in position 11 of the protospacer). The nucleotides substituted by base editing are shown in red. b Experimental design: 10-week-old hPCSK9-KI mice were transduced with adenoviral vectors (AdV) encoding BE3 alone (control) or BE3 together with gMH. Blood was collected 3 days before injection (baseline); the blood and liver were collected 3 weeks after injection. c, d Plasma concentrations of human and mouse PCSK9 proteins 3 weeks after BE3 treatment (normalized to plasma concentrations at baseline; n = 8 per group). e Plasma concentrations of total cholesterol (CHO) 3 weeks after BE3 treatment (normalized to plasma concentrations at baseline; n = 8 per group). Data were pooled from two independent experiments and analyzed with one-way ANOVA and Dunnett’s correction for multiple testing. Values are presented as group means ± SEM. *p < 0.05; **p < 0.001