medicine |
construction of lentiviral vectors containing the human purine-nucleoside phosphorylase gene and transduction of lymphocytes from a purine nucelotide phosphorylase-deficient patient as well as lymphocytes, fibroblasts and bone marrow from purine nucelotide phosphorylase-deficient mice. Transduction significantly increases purine nucelotide phosphorylase expression in purine nucelotide phosphorylase-deficient human lymphocytes, murine lymphocytes, fibroblasts and bone marrow cells. Lenti-purine nucelotide phosphorylase transduction also significantly improves the proliferation of PNP-/- murine lymphocyte and survival of irradiated purine nucelotide phosphorylase-/- fibroblasts. Transduced purine nucelotide phosphorylase-/- bone marrow cells transplanted into purine nucelotide phosphorylase-/- mice express purine nucelotide phosphorylase in vivo, partially restore urinary uric acid secretion, show improved thymocytes maturation, increased weight gain and extended survival of the mice. 12 weeks after transplant, the benefit of lenti-purine nucelotide phosphorylase transduced cells and normal bone marrow diminishes and the percentage of engrafted donor cells decrease |
Homo sapiens |