Targeted transgene expression in rat brain using lentiviral vectors
Targeted transgene expression in rat brain using lentiviral vectors
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DOI：
10.1002/jnr.10719
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发表时间：
2003-09-15
影响因子：
4.2
通讯作者：
Lundberg, C
中科院分区：
文献类型：
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作者：
Jakobsson, J;Ericson, C;Lundberg, C
直接基因转移到成人大脑依赖于转导非分裂细胞的载体，如慢病毒载体。大脑基因治疗发展的另一个方面是需要细胞特异性的转基因表达。据报道，水疱性口炎病毒g蛋白（VSV-G）假型慢病毒载体在大脑中的表达主要是神经元特异性的。我们使用神经元特异性烯醇化酶（rNSE）或胶质纤维酸性蛋白（hGFAP）启动子构建细胞特异性慢病毒载体，并将它们与普遍存在的人巨细胞病毒启动子（hCMV）、CMV/ β -肌动蛋白混合启动子（CAG）和人延伸因子1 α启动子（ef1 α）进行比较。我们的结果显示，hGFAP启动子仅在神经胶质细胞中表达，而rNSE则纯粹是神经元特异性的，这表明VSV-G在大鼠纹状体中是泛性的。我们得出结论，VSV-G允许神经胶质细胞和神经元细胞的转导，启动子决定了转基因将在哪种细胞类型中表达。仅在星形胶质细胞中表达转基因将允许局部递送分泌的转基因产物，如胶质细胞系衍生的神经营养因子（GDNF），避免可能引起不良副作用的顺行运输。(C) 2003 Wiley-Liss, Inc。
Direct gene transfer to the adult brain is dependent on vectors that transduce non-dividing cells, such as lentiviral vectors. Another aspect of the development of gene therapy to the brain is the need for cell-specific transgene expression. Expression from vesicular stomatitis virus G-protein (VSV-G) pseudotyped lentiviral vectors has been reported to be mainly neuron specific in the brain. We constructed cell-specific lentiviral vectors using the neuron-specific enolase (rNSE) or the glial fibrillary acidic protein (hGFAP) promoters and compared them to the ubiquitous human cytomegalovirus promoter (hCMV), a hybrid CMV/beta-actin promoter (CAG) and the promoter for human elongation factor 1alpha (EF1alpha). Our results showed that the hGFAP promoter was expressed only in glial cells, whereas rNSE was purely neuron specific, showing that VSV-G is pantropic in the rat striatum. We conclude that the VSV-G allows transduction of both glial and neuronal cells and the promoter dictates in what cell type the transgene will be expressed. The expression of transgenes exclusively in astrocytes would allow for local delivery of secreted transgene products, such as glial cell line-derived neurotrophic factor (GDNF), circumventing the anterograde transport that may induce unwanted side effects. (C) 2003 Wiley-Liss, Inc.