CORRECTION OF LYSOSOMAL STORAGE IN THE LIVER AND SPLEEN OF MPS-VII MICE BY IMPLANTATION OF GENETICALLY-MODIFIED SKIN FIBROBLASTS

Genetic defects of lysosomal hydrolases result in severe storage disea ses 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 aut ologous implants of genetically-modified skin fibroblasts for the cont inuous in vivo production of the enzyme. The human beta-glucuronidase cDNA was introduced with a retroviral vector into mutant mice skin fib roblasts grown in primary culture. Fourteen mutant mice were implanted intraperitoneally with these modified cells embedded into collagen la ttices. All animals expressed beta-glucuronidase from the vascularized neo-organs that developed after implantation and accumulated the enzy me in their tissues. A complete disappearance of the lysosomal storage lesions was observed in their liver and spleen.