Fig. 3.

AAV-delivery of NmeCas9 for in vivo genome editing. a Experimental outline of AAV8-sgRNA-hNmeCas9 vector tail-vein injections to target Pcsk9 (sgPcsk9) and Rosa26 (sgRosa26) in C57Bl/6 mice. Mice were sacrificed at 14 (n = 1) or 50 days (n = 5) post injection and liver tissues were harvested. Blood sera were collected at days 0, 25, and 50 post injection for cholesterol level measurement. b Serum cholesterol levels. p values are calculated by unpaired t test. c Stacked histogram showing the percentage distribution of indels at Pcsk9 or Rosa26 in livers of mice, as measured by targeted deep-sequencing analyses. Data are presented as mean ± SD from five mice per cohort. d A representative anti-PCSK9 western blot using total protein collected from day 50 mouse liver homogenates. A total of 2 ng of recombinant mouse PCSK9 (r-PCSK9) was included as a mobility standard. The asterisk indicates a cross-reacting protein that is larger than the control recombinant protein