Metabolic correction and cross-correction of mucopolysaccharidosis type II (Hunter syndrome) by retroviral-mediated gene transfer and expression of human iduronate-2-sulfatase

Stephen E. Braun, Elena L. Aronovich, Rose Ann Anderson, Paul L. Crotty, R. Scott McIvor, Chester B. Whitley

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

To explore the possibility of using gene transfer to provide iduronate-2-sulfatase (IDS; EC 3.1.6.13) enzyme activity for treatment of Hunter syndrome, an amphotropic retroviral vector, L2SN, containing the human IDS coding sequence was constructed and studied for gene expression in vitro. Lymphoblastoid cell lines (LCLs) from patients with Hunter syndrome were transduced with L2SN and expressed high levels of IDS enzyme activity, 10- to 70-fold higher than normal human peripheral blood leukocytes or LCLs. Such L2SN-transduced LCLs failed to show accumulation of 35SO4 into glycosaminoglycan (35SO4-GAG), indicating that recombinant IDS enzyme participated in GAG metabolism. Coculture of L2SN-transduced LCLs with fibroblasts from patients with Hunter syndrome reduced the accumulation of 35SO4-GAG. These results demonstrated retroviral-mediated IDS gene transfer into lymphoid cells and the ability of such cells to provide recombinant enzyme for intercellular metabolic cross-correction.

Original languageEnglish (US)
Pages (from-to)11830-11834
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number24
DOIs
StatePublished - Dec 15 1993

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