Efficient therapeutic gene expression in cultured rat hippocampal neurons mediated by human foamy virus vectors: a potential for the treatment of neurological diseases.
Vectors derived from human foamy virus (HFV), with their nonpathogenic nature and a wide tissue tropism, have been successfully used as retroviral gene transfer vehicles. However, transduction of primary hippocampal neurons (HNs) with HFV vectors has little been studied. To investigate the potential of HFV-derived vector in gene therapy for neurological diseases, efficient foreign gene expression in cultured rat HNs was first demonstrated by successful enhanced green fluorescent protein (EGFP) transduction through a HFV vector bearing an EGFP expression cassette. Furthermore, we tested the effect on HNs that were transduced by a novel HFV vector expressing the human glutamic acid decarboxylase (GAD) cDNA, a therapeutic gene for neurological disorders such as epilepsy and Parkinson's disease. The transduced HNs showed significant increase in isoform-specific expression of GAD, synthesis of gamma-aminobutyric acid (GABA) and stimulation-evoked GABA release. These findings indicated for the first time that cultured rat HNs could be efficiently transduced by HFV vectors, and the GAD-expressing HFV vector has potential therapeutic value in the treatment of neurological diseases.
Liu
Wanhong
W
Key Laboratory of Virology, Ministry of Education, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
He
Xiaohua
X
Cao
Zhijian
Z
Sheng
Jiqun
J
Liu
Hui
H
Li
Zhi
Z
Li
Wenxin
W
D000818:Animals; D002478:Cells, Cultured; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009422:Nervous System Diseases / Q000628:therapy*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016092:Spumavirus / Q000235:genetics*; D014161:Transduction, Genetic; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase