Trophic activity of Rabies G protein-pseudotyped equine infectious anemia viral vector mediated IGF-I motor neuron gene transfer in vitro |
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Authors: | Teng Qingshan Garrity-Moses Mary Federici Thais Tanase Diana Liu James K Mazarakis Nicholas D Azzouz Mimoun Walmsley Lucy E Carlton Erin Boulis Nicholas M |
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Affiliation: | Department of Neuroscience and Center for Neurological Restoration, Lerner Research Institute, Cleveland Clinic Foundation, NB2-126, 9500 Euclid Avenue, Cleveland, OH 44195, USA. |
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Abstract: | The present study examines gene delivery to cultured motor neurons (MNs) with the Rabies G protein (RabG)-pseudotyped lentiviral equine infectious anemia virus (RabG.EIAV) vector. RabG.EIAV-mediated beta-galactosidase (RabG.EIAV-LacZ) gene expression in cultured MNs plateaus 120 h after infection. The rate and percent of gene expression observed are titer-dependent (P < 0.001). The rat IGF-I cDNA sequence was then cloned into a RabG.EIAV vector (RabG.EIAV-IGF-I) and was shown to induce IGF-I expression in HEK 293 cells. MNs infected with RabG.EIAV-IGF-I demonstrate enhanced survival compared to MNs infected with RabG.EIAV-LacZ virus (P < 0.01). In addition, IGF-I expression in cultured MNs induced profound MN axonal elongation compared to control virus (P < 0.01). The enhanced motor neuron tropism of RabG.EIAV previously demonstrated in vivo, together with the trophic effects of RabG.EIAV-IGF-I MN gene expression may lend this vector to therapeutic application in motor neuron disease. |
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Keywords: | Amyotrophic lateral sclerosis Lentiviral vector Gene therapy Pseudotyping Neurotrophic factor Insulin-like growth factor Retrograde axonal transport |
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