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• W2020819071 abstract "X-linked adrenoleukodystrophy (ALD), an inherited demyelinating disorder of the central nervous system, can be corrected by allogeneic bone marrow transplantation, likely due to the turnover of brain macrophages that are bone marrow derived. ALD is characterized by an accumulation of very long chain fatty acids (VLCFA) due to the deficiency of an ATP binding cassette transporter that imports these fatty acids in peroxisomes. Murine retroviral transduction results in metabolic correction of ALD CD34+ cells in vitro but reinfusion of these cells into ALD patients would not provide clinical benefit owing to the absence of selective advantage conferred by transgene expression. High-efficiency transduction of ALD CD34+ peripheral blood mobilized cells was achieved using an HIV-based vector driving ALD gene expression under the elongation factor 1α promoter and a protocol without prestimulation of CD34+ cells with cytokines prior to transduction to preserve their stem cell properties. Efficient expression of the ALD gene was demonstrated in monocytes/macrophages derived from cultures of transduced ALD CD34+ cells and in long-term culture initiating cells. VLCFA metabolism was corrected in transduced CD34+, CFU-derived, and LTC-derived cells, indicating that the vector-encoded ALD protein was fully functional. Transplantation of transduced ALD CD34+ cells into NOD/SCID mice resulted in long-term expression of ALD protein in monocytes/macrophages derived from engrafted stem cells." @default.
• W2020819071 created "2016-06-24" @default.
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• W2020819071 date "2003-03-01" @default.
• W2020819071 modified "2023-10-02" @default.
• W2020819071 title "Transduced CD34+ cells from adrenoleukodystrophy patients with HIV-derived vector mediate long-term engraftment of NOD/SCID mice" @default.
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• W2020819071 doi "https://doi.org/10.1016/s1525-0016(03)00002-9" @default.
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