Trophic activity of Rabies G protein-pseudotyped equine infectious anemia viral vector mediated IGF-I motor neuron gene transfer in vitro.
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.
Teng
Qingshan
Q
Department of Neuroscience and Center for Neurological Restoration, Lerner Research Institute, Cleveland Clinic Foundation, NB2-126, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Garrity-Moses
Mary
M
Federici
Thais
T
Tanase
Diana
D
Liu
James K
JK
Mazarakis
Nicholas D
ND
Azzouz
Mimoun
M
Walmsley
Lucy E
LE
Carlton
Erin
E
Boulis
Nicholas M
NM
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D020439:Growth Cones / Q000378:metabolism / Q000821:virology; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009046:Motor Neurons / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism / Q000821:virology; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000235:genetics
D009414:Nerve Growth Factors; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C073777:glycoprotein G (29-41), rabies virus; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1