Prolonged correction of hyperlipidemia in mice with familial hypercholesterolemia using an adeno-associated viral vector expressing very-low-density lipoprotein receptor

Adeno-associated viral vectors were used to deliver the gene for very-low-d ensity lipoprotein (VLDL) receptor (VLDLR) to river of a murine model of fa milial hypercholesterolemia (FH). Infusion of adeno-associated virus-VLDLR into the portal circulation of FH mice resulted in a 40% reduction in serum cholesterol and triglyceride that was stable for the duration of the study (30 weeks). Fractionation of serum lipids revealed a reduction of both VLD L and low-density lipoprotein. Expression of transgene-derived VLDLR was co nfirmed in livers of recipient animals by Western blot analysis and immunoh istochemistry; vector DNA was present at 1 copy/cell. Vector-treated animal s had significantly less lipid accumulation in liver and reduced atheroscle rosis in the aorta.