Restoration of normal lysosomal function in mucopolysaccharidosis type VII cells by retroviral vector-mediated gene transfer

J. H. Wolfe, E. H. Schuchman, L. E. Stramm, E. A. Concaugh, M. E. Haskins, G. D. Aguirre, D. F. Patterson, R. J. Desnick, E. Gilboa

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58 Scopus citations


Retroviral vectors were constructed containing a rat β-glucuronidase cDNA driven by heterologous promoters. Vector-mediated gene transfer into human and canine β-glucuronidase-deficient mucopolysaccharidosis type VII fibroblasts completely corrected the deficiency in β-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, β-glucuronidase was expressed at high levels in transduced cells. Thus, the vector-encoded β-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.

Original languageEnglish (US)
Pages (from-to)2877-2881
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Jan 1 1990



  • β-glucuronidase
  • Animal models
  • Gene therapy
  • Lysosomal storage diseases
  • Substrate degradation

ASJC Scopus subject areas

  • Genetics
  • General

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