In particular, a single injection of a GOF murine PCSK9 mutant plasmid (pAAV/D377Y-mPCSK9) into C57 mice to effectively knockdown LDLR resulted in significant hypercholesterolemia and subsequent atherosclerosis development within 3 months without the need of germline knockout of ApoE or LDLR [88]. Here, PCSK9 is linked to atherosclerosis.