We previously evaluated an adeno-associated virus (AAV) vector-delivered, liver-directed meganuclease for in vivo gene editing of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) gene.19–21 PCSK9 is an antagonist of the low-density lipoprotein (LDL) receptor, meaning that a loss of function of PCSK9 reduces LDL levels; therefore, this approach could be useful in the treatment of hypercholesterolemia. Here, PCSK9 is linked to familial hypercholesterolemia.