In vivo studies in an AD mouse model revealed that ten or three intravenous injections of Cas9/sgRNA pDNA-loaded nanosystem targeting the Bace1 gene downregulated ~ 20% of the expression of BACE1 in the mice and reduced ~ 50% of the amyloid-β plaque area in the hippocampus of 2xTg-AD mice. Here, BACE1 is linked to Alzheimer disease.