We applied v3em PE3-AAV to install mutations of biomedical interest in mice that are not currently accessible with other in vivo genome editing technologies, including the rare Apolipoprotein E Christchurch (APOE3 R136S) variant that may alter Alzheimer’s disease (AD) risk and the dominant variant of proprotein convertase subtilisin/kexin type 9 (PCSK9) Q152H (mouse Pcsk9 Q155H) that is associated with a reduction in low-density lipoprotein (LDL) cholesterol levels and protection from coronary artery disease. This evidence concerns the gene PCSK9 and Alzheimer disease.