Curr Drug Targets. 2013 Oct;14(11):1336-46. doi: 10.2174/13894501113146660213.
The morphological and functional diversity of astrocytes, and their essential contribution in physiological and pathological conditions, are starting to emerge. However, experimental systems to investigate neuron-glia interactions and develop innovative approaches for the treatment of central nervous system (CNS) disorders are still very limited. Fluorescent reporter genes have been used to visualize populations of astrocytes and produce an atlas of gene expression in the brain. Knock-down or knock-out of astrocytic proteins using transgenesis have also been developed, but these techniques remain complex and time-consuming. Viral vectors have been developed to overexpress or silence genes of interest as they can be used for both in vitro and in vivo studies in adult mammalian species. In most cases, high transduction efficiency and long-term transgene expression are observed in neurons but there is limited expression in astrocytes. Several strategies have been developed to shift the tropism of lentiviral vectors (LV) and allow local and controlled gene expression in glial cells. In this review, we describe how modifications of the interaction between the LV envelope glycoprotein and the surface receptor molecules on target cells, or the integration of cell-specific promoters and miRNA post-transcriptional regulatory elements have been used to selectively express transgenes in astrocytes.
星形胶质细胞的形态和功能多样性，以及它们在生理和病理条件下的重要贡献，正开始显现出来。然而，用于研究神经元-胶质细胞相互作用和开发中枢神经系统 (CNS) 疾病治疗创新方法的实验系统仍然非常有限。荧光报告基因已被用于可视化星形胶质细胞群体，并绘制大脑中基因表达图谱。使用转基因技术敲低或敲除星形胶质细胞蛋白的方法也已经开发出来，但这些技术仍然很复杂且耗时。病毒载体已被开发用于过表达或沉默感兴趣的基因，因为它们可用于成年哺乳动物物种的体外和体内研究。在大多数情况下，在神经元中观察到高转导效率和长期转基因表达，但在星形胶质细胞中的表达有限。已经开发了几种策略来改变慢病毒载体 (LV) 的嗜性，并允许在神经胶质细胞中进行局部和受控的基因表达。在这篇综述中，我们描述了如何修饰 LV 包膜糖蛋白与靶细胞表面受体分子之间的相互作用，或整合细胞特异性启动子和 miRNA 转录后调控元件，以选择性地在星形胶质细胞中表达转基因。
