Reversal of pathology in murine mucopolysaccharidosis type VII by somatic cell gene transfer

John H. Wolfe, Mark S. Sands, Jane E. Barker, Babette Gwynn, Lucy B. Rowe, Carole A. Vogler, Edward H. Birkenmeier

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


AN inherited deficiency of glucuronidase in humans1, mice 2 and dogs3 causes mucopolysaccharidosis VII (Sly syndrome), a progressive degenerative disease that reduces lifespan (to an average of 5 months in mice2) and results from lysosomal storage of undegraded glycosaminoglycans in the spleen, liver, kidney, cornea, brain and skeletal system1-4. Bone marrow transplantation in mutant mice provides a source of normal enzyme ('cross-correction'5), which substantially improves the clinical condition and extends the average lifespan to 18 months6. Gene therapy by transfer of a glucuronidase gene into mutant haematopoietic stem cells is an alternative approach7,8, but it is not known whether the low expression of vector-transferred genes 9,10 would be sufficiently effective. Here we show that retroviral vector-mediated transfer of the gene to mutant stem cells results in long-term expression of low levels of glucuronidase which partially corrects the disease by reducing lysosomal storage in liver and spleen.

Original languageEnglish
Pages (from-to)749-753
Number of pages5
Issue number6406
StatePublished - Jan 1 1992


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