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Gene delivery targeted to oligodendrocytes using a lentiviral vector.

Abstract
Most leukodystrophies result from mutations in genes expressed in oligodendrocytes that may cause autonomous loss of function of cell structural proteins. Therefore, effective gene delivery to oligodendrocytes is necessary to develop future treatments.

To achieve this, we cloned a lentiviral vector in which the enhanced green fluorescent protein (EGFP) expression was driven by the oligodendrocyte specific 2,3-cyclic nucleotide 3-phosphodiesterase promoter. The vector was inserted into C57BL/6 neonatal mouse brain by combined intraventricular and parenchymal injections.
Assessment of EGFP expression revealed a widespread distribution, specifically in cells of the oligodendrocyte linage, starting from postnatal day 6 (P6) in the subventricular zone and spreading through migrating oligodendrocyte precursors. By P30, it was detectable throughout the brain and persisted for at least 3 months, showing an increase both in the number of expressing cells and in intensity over time. EGFP expression was restricted to oligodendrocyte linage cells. On average, 20.3 ± 2.56% of all oligodendrocytes in different central nervous system areas were EGFP-positive, with regional variations.