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pubmed-article:9195213pubmed:abstractTextDisorders in which there is toxic buildup of circulating substrate may be treated by furnishing an enzyme reservoir capable of metabolically processing the excess substrate. The epidermal keratinocyte is a potential site for such a reservoir. In this study, we explore the capacity of genetically modified keratinocytes to metabolize extracellular substrate in a culture model that resembles in vivo epidermal architecture. Keratinocytes from adenosine deaminase (ADA)-deficient patients were transduced with a retroviral vector encoding the human ADA gene and the capacity of this tissue to deaminate deoxyadenosine (dAdo) in vitro was measured. The results show that at a substrate concentration of 10 microM, ADA-corrected keratinocytes deaminate dAdo at a rate of 0.38 nmol/min.10(6) cells. These results indicate that keratinocytes process extracellular substrate at rates that suggest complete substrate conversion in a single pass. This study provides a strong indication that the epidermis, the largest and most accessible tissue of the body, is a valuable site for designing clinically relevant gene therapies.lld:pubmed
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pubmed-article:9195213pubmed:authorpubmed-author:BlaeseR MRMlld:pubmed
pubmed-article:9195213pubmed:authorpubmed-author:SchwartzP MPMlld:pubmed
pubmed-article:9195213pubmed:authorpubmed-author:TaichmanL BLBlld:pubmed
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pubmed-article:9195213pubmed:pagination911-7lld:pubmed
pubmed-article:9195213pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:9195213pubmed:year1997lld:pubmed
pubmed-article:9195213pubmed:articleTitleKeratinocyte gene therapy for adenosine deaminase deficiency: a model approach for inherited metabolic disorders.lld:pubmed
pubmed-article:9195213pubmed:affiliationDepartment of Oral Biology and Pathology, State University of New York at Stony Brook 11794, USA.lld:pubmed
pubmed-article:9195213pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:9195213pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:9195213pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
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