Efficient gene transfer and expression of biologically active glial cell line-derived neurotrophic factor in rat motoneurons transduced with lentiviral vectors

Several studies have shown the ability of human immunodeficiency virus type 1 (HIV1)-based lentiviral vectors to infect nondividing brain and retinal neurons with high efficiency and long-term expression of the transduced gen e. We show that purified embryonic motoneurons can be efficiently (>95%) tr ansduced in culture using an HIV1-based lentiviral vector encoding LacZ. Ex pression of beta-galactosidase was observed for at least 9 days in these co nditions. Furthermore, motoneurons transduced with a lentiviral vector expr essing glial cell line-derived neurotrophic factor survived in the absence of additional trophic support, showing that the overexpressed protein was b iologically active. Our results demonstrate the potential of lentiviral vec tors in studying the biological effects of proteins expressed in motoneuron s and in the development of future gene therapy for motoneuron diseases.