title: Lifetime correction of genetic deficiency in mice with a single injection of helper-dependent adenoviral vector.
abstract: Ideally, somatic gene therapy should result in lifetime reversal of genetic deficiencies. However, to date, phenotypic correction of monogenic hyperlipidemia in mouse models by in vivo gene therapy has been short-lived and associated with substantial toxicity. We have developed a helper-dependent adenoviral vector (HD-Ad) containing the apolipoprotein (apo) E gene. A single i.v. injection of this vector completely and stably corrected the hypercholesterolemia in apoE-deficient mice, an effect that lasted the natural lifespan of the mice. At 2.5 years, control aorta was covered 100% by atherosclerotic lesion, whereas aorta of treated mice was essentially lesion-free. There was negligible toxicity associated with the treatment. We also developed a method for repeated HD-Ad vector administration that could be applied to organisms, e.g., humans, with life spans longer than 2-3 years. These studies indicate that HD-Ad is a promising system for liver-directed gene therapy of metabolic diseases.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: I H
authors.initials: IH
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Józkowicz
authors.forename: P A
authors.initials: PA
authors.lastname: Piedra
authors.forename: K
authors.initials: K
authors.lastname: Oka
authors.forename: L
authors.initials: L
authors.lastname: Chan
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006937:Hypercholesterolemia / Q000235:genetics* / Q000628:therapy*; D007150:Immunohistochemistry; D008017:Life Expectancy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers