Mobilization and transduction of peripheral blood progenitor cells in patients with mucopolysaccharidosis I

Mucopolysaccharidosis type I (MPS I) results from a deficiency of alpha-L-i duronidase enzyme (IDUA), an enzyme responsible for the catabolism of glyco saminoglycans, Genetically modified progenitor cells may permit a therapeut ic effect similar to that obtained from allogeneic BMT without the associat ed risks. To that end, CD34+ peripheral blood hematopoietic progenitor cell s from patients with MPS I were mobilized using G-CSF, collected by apheres is, and enriched using avidin-biotin separation techniques. These cells wer e cultured in a hollow fiber bioreactor and transduced with a retroviral ve ctor (LP1CD) containing the cDNA for human IDUA and a murine dihydrofolate reductase (DHFR) enzyme. Approximately 4%-16% of the colonies expressed met hotrexate drug resistance. Expression of the IDUA enzyme in the progenitor cells was initially high and declined after approximately 10 days of cultur e. These results indicate that PBPC from patients with MPS I can be mobiliz ed, isolated, enriched, and transduced with a therapeutic gene.