Molecular Therapy
Volume 2, Issue 3, September 2000, Pages 256-261
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Article
Prolonged Correction of Hyperlipidemia in Mice with Familial Hypercholesterolemia Using an Adeno-Associated Viral Vector Expressing Very-Low-Density Lipoprotein Receptor

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Adeno-associated viral vectors were used to deliver the gene for very-low-density lipoprotein (VLDL) receptor (VLDLR) to liver of a murine model of familial 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 VLDL and low-density lipoprotein. Expression of transgene-derived VLDLR was confirmed in livers of recipient animals by Western blot analysis and immunohistochemistry; vector DNA was present at 1 copy/cell. Vector-treated animals had significantly less lipid accumulation in liver and reduced atherosclerosis in the aorta.

Key Words

gene therapy
liver
cellular immunity

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Abbreviations used: FH, familial hypercholesterolemia; AAV, adeno-associated virus; VLDL, very low-density lipoproteins; LDL, low-density lipoproteins: IDL, intermediate density lipoproteins.