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

Mol Ther. 2000 Sep;2(3):256-61. doi: 10.1006/mthe.2000.0122.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dependovirus / genetics*
  • Gene Transfer Techniques
  • Genetic Vectors*
  • Hyperlipidemias / therapy*
  • Hyperlipoproteinemia Type II / therapy*
  • Mice
  • Receptors, LDL / genetics*


  • Receptors, LDL
  • VLDL receptor