Differential characteristics of HIV-based versus SIV-based lentiviral vector systems: Gene delivery to neurons and axonal transport of expressed gene
Differential characteristics of HIV-based versus SIV-based lentiviral vector systems: Gene delivery to neurons and axonal transport of expressed gene
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DOI：
10.1016/j.neures.2006.12.016
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发表时间：
2007-04-01
影响因子：
2.9
通讯作者：
Shimada, Takashi
中科院分区：
文献类型：
--
作者：
Kitagawa, Ryo;Miyachi, Shigehiro;Shimada, Takashi
在大鼠和猴中研究了基于人类和猿免疫缺陷病毒（HIV和SIV）的慢病毒载体的差异特征。将每个载体注射到纹状体中，并分析基底神经节中标记基因绿色荧光蛋白（GFP）的表达模式。关于基因递送到神经细胞的能力，基于HIV的载体对纹状体中的神经元比对星形胶质细胞表现出更高的向性，并且基于SIV的载体反之亦然。在本研究中还检查了纹状体表达的GFP的轴突运输的优先方向。基于HIV的载体允许通过striatopallidal和striatonigral途径的顺行运输和通过nigrostriatal途径的逆行运输。无论动物种属如何，轴突终末通过顺行运输的GFP标记都是明显的，而神经元细胞体通过逆行运输的GFP标记在猴子中比在大鼠中更为突出。另一方面，对于SIV载体，在猴子中获得的顺行转运证据比在大鼠中明显得多，并且在猴子或大鼠中仅发生微弱或没有逆行转运。我们的研究结果表明，艾滋病毒为基础的，但不是SIV为基础的，慢病毒载体具有高度的向性神经元，并允许逆行运输的表达基因，特别是在灵长类动物。后一种性质可能在帕金森病的基因治疗中具有潜在的益处，因为载体的立体定位注射可以在空间上大于黑质的纹状体中进行，具有更大的确定性。(c)2007 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
The differential characteristics of lentiviral vectors based on human and simian immunodeficiency viruses (HIV and SIV) were investigated in rats and monkeys. Each vector was injected into the striatum, and the expression patterns of the marker gene green fluorescent protein (GFP) were analyzed in the basal ganglia. With respect to the capability of gene delivery to neural cells, the HIV-based vector exhibited a higher tropism to neurons than to astroglias in the striatum, and vice versa for the SIV-based vector. The preferential direction of axonal transport of striatally expressed GFP was also examined in the present study. The HIV-based vector allowed for both anterograde transport via the striatopallidal and striatonigral pathways and retrograde transport via the nigrostriatal pathway. The GFP labeling of axon terminals through anterograde transport was apparent regardless of the animal species, while that of neuronal cell bodies through retrograde transport was much more prominent in monkeys than in rats. As for the SIV-based vector, on the other hand, evidence for anterograde transport was obtained much more markedly in monkeys than in rats, and only weak or no retrograde transport occurred in either monkeys or rats. Our results indicate that HIV-based, but not SIV-based, lentiviral vectors possess the high tropism to neurons and permit retrograde transport of an expressed gene, especially in primates. The latter property might carry a potential benefit in gene therapy for Parkinson's disease, as stereotaxic injections of the vectors could be performed into the striatum, spatially larger than the substantia nigra, with greater certainty. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.