Recombinant human foamy virus, a novel vector for neurological disorders gene therapy, drives production of GAD in cultured astrocytes.
Human foamy virus (HFV), with its nonpathogenic nature and several unique features for gene transfer, is a promising vector system for neurological disorders gene therapy. The question of whether HFV vectors can be developed for the expression of therapeutic genes in primary astrocytes of the brain may be of interest. First, efficient expression for foreign genes, which is critical for the potentials of HFV-derived vector in gene therapy, was successfully demonstrated in rat-cultured astrocytes by the enhanced green fluorescent protein (EGFP) transduction through an HFV vector bearing an EGFP expression cassette. Second, HFV vectors containing human glutamic acid decarboxylase (GAD) complementary DNA, which encodes an inhibitory neurotransmitter gamma-aminobutyric acid (GABA)-producing enzyme, were used to examine the function of GAD on GABA synthesis in cultured astrocytes. We found that the transduction of GAD vector resulted in isoform-specific expression of GAD, synthesis of a significant amount of GABA and tonical GABA release, and behavioral recovery in rat Parkinson's disease (PD) models. These results suggested that HFV vector had the ability to transduce astrocytes and HFV vector-derived GAD expression in astrocytes provided a potential strategy for the treatment of neurological disorders associated with hyperexcitable or diminished inhibitory activity.
Liu
Wanhong
W
School of Medicine, Wuhan University, Wuhan, P.R. China.
Liu
Zhongchun
Z
Cao
Xiongbin
X
Cao
Zhijian
Z
Xue
Lu
L
Zhu
Fan
F
He
Xiaohua
X
Li
Wenxin
W
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D001522:Behavior, Animal; D002460:Cell Line; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D015316:Genetic Therapy; D005822:Genetic Vectors; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D009422:Nervous System Diseases / Q000201:enzymology / Q000378:metabolism / Q000628:therapy*; D011995:Recombination, Genetic; D016092:Spumavirus / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase