PCSK9 and cardiovascular disorder: Two sites in the mouse genome were selected initially to test the nuclease activity of NmeCas9 in vivo: the Rosa26 “safe-harbor” gene (targeted by sgRosa26); and the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene (targeted by sgPcsk9), a common therapeutic target for lowering circulating cholesterol and reducing the risk of cardiovascular disease (Fig. 1b).