AAV-PCSK9 D377Y

AAV-PCSK9 D377Y (also known as AAV8-mPCSK9-D377Y) is a recombinant adeno-associated viral (AAV) vector, typically of the AAV8 serotype, used as a preclinical research tool to induce hypercholesterolemia and atherosclerosis in mouse models. It encodes a gain-of-function mutant form of murine Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) with a D377Y substitution, which is the murine equivalent of the human D374Y mutation associated with autosomal-dominant hypercholesterolemia. Upon a single intraperitoneal injection, the vector targets the liver to express and secrete the mutant PCSK9 protein, which subsequently binds to and promotes the degradation of the Low-Density Lipoprotein Receptor (LDLR). This mechanism leads to rapid and sustained increases in plasma LDL cholesterol levels, allowing researchers to study cardiovascular and metabolic phenotypes in wild-type mice (e.g., C57BL/6J) without the need for germline genetic modifications such as Ldlr or ApoE knockouts. It is widely utilized in research supported by institutions like the NIH and is commercially available as a plasmid or viral preparation through Addgene.

Other names

AAV-PCSK9 D377YAAV-PCSK-9 D377YAAV-PCSK 9 D377Y