Treatment of lysosomal storage disease in MPS VII mice using a recombinantadeno-associated virus

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease cau sed by a genetic deficiency of beta-glucuronidase. We used a recombinant ad eno-associated virus vector (AAV-GUS) to deliver GUS cDNA to MPS VII mice. The route of vector administration had a dramatic effect on the extent and distribution of GUS activity. Intramuscular injection of AA V-GUS resulted in high, localized production of GUS, while intravenous administration prod uced low GUS activity in several tissues. This latter treatment of MPS VII mice reduced glycosaminoglycan levels in the liver to normal and reduced st orage granules dramatically. We show that a single administration of AAV-GU S can provide sustained expression of GUS in a variety of cell types and is sufficient to reverse the disease phenotype at least in the liver.