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-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.
Chen
S J
SJ
Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
Rader
D J
DJ
Tazelaar
J
J
Kawashiri
M
M
Gao
G
G
Wilson
J M
JM
D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006949:Hyperlipidemias / Q000628:therapy*; D006938:Hyperlipoproteinemia Type II / Q000628:therapy*; D051379:Mice; D011973:Receptors, LDL / Q000235:genetics*
D011973:Receptors, LDL; C036053:VLDL receptor