title: Correction of lysosomal storage in the liver and spleen of MPS VII mice by implantation of genetically modified skin fibroblasts.
abstract: Genetic defects of lysosomal hydrolases result in severe storage diseases and treatments based on enzyme replacement have been proposed. In mice lacking beta-glucuronidase, which develop a disease homologous to human mucopolysaccharidosis type VII (Sly syndrome), we have used autologous implants of genetically-modified skin fibroblasts for the continuous in vivo production of the enzyme. The human beta-glucuronidase cDNA was introduced with a retroviral vector into mutant mice skin fibroblasts grown in primary culture. Fourteen mutant mice were implanted intraperitoneally with these modified cells embedded into collagen lattices. All animals expressed beta-glucuronidase from the vascularized neo-organs that developed after implantation and accumulated the enzyme in their tissues. A complete disappearance of the lysosomal storage lesions was observed in their liver and spleen.
authors.affiliation: Laboratoire Rétrovirus et Transfert Génétique, Institut Pasteur, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Moullier
authors.forename: D
authors.initials: D
authors.lastname: Bohl
authors.forename: J M
authors.initials: JM
authors.lastname: Heard
authors.forename: O
authors.initials: O
authors.lastname: Danos
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000201:enzymology / Q000637:transplantation*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005966:Glucuronidase / Q000008:administration & dosage / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use; D006025:Glycosaminoglycans / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D016538:Mucopolysaccharidosis VII / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009928:Organ Specificity; D010529:Peritoneal Cavity; D010641:Phenotype; D019736:Prostheses and Implants; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000201:enzymology* / Q000473:pathology; D014162:Transfection
chemical_list: D006025:Glycosaminoglycans; D011993:Recombinant Fusion Proteins; D005966:Glucuronidase