title: Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer.
abstract: Retroviral vectors were constructed containing a rat beta-glucuronidase cDNA driven by heterologous promoters. Vector-mediated gene transfer into human and canine beta-glucuronidase-deficient mucopolysaccharidosis type VII fibroblasts completely corrected the deficiency in beta-glucuronidase enzymatic activity. In primary cultures of canine mucopolysaccharidosis type VII retinal pigment epithelial cells, which contain large amounts of undegraded glycosaminoglycan substrates, vector correction restored normal processing of specific glycosaminoglycans in the lysosomal compartment. In canine mucopolysaccharidosis type VII bone marrow cells, beta-glucuronidase was expressed at high levels in transduced cells. Thus, the vector-encoded beta-glucuronidase was expressed at therapeutic levels in the appropriate organelle and corrected the metabolic defect in cells exhibiting the characteristic pathology of this lysosomal storage disorder.
authors.affiliation: Laboratory of Pathology, University of Pennsylvania School of Veterinary Medicine, Philadelphia 19104.
authors.forename: J H
authors.initials: JH
authors.lastname: Wolfe
authors.forename: E H
authors.initials: EH
authors.lastname: Schuchman
authors.forename: L E
authors.initials: LE
authors.lastname: Stramm
authors.forename: E A
authors.initials: EA
authors.lastname: Concaugh
authors.forename: M E
authors.initials: ME
authors.lastname: Haskins
authors.forename: G D
authors.initials: GD
authors.lastname: Aguirre
authors.forename: D F
authors.initials: DF
authors.lastname: Patterson
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
authors.forename: E
authors.initials: E
authors.lastname: Gilboa
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000201:enzymology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology; D005822:Genetic Vectors; D005966:Glucuronidase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D009083:Mucopolysaccharidoses / Q000201:enzymology / Q000235:genetics*; D051381:Rats; D013539:Simian virus 40 / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics*; D012867:Skin / Q000201:enzymology; D014162:Transfection
chemical_list: D005966:Glucuronidase