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.
Keywords: Astrocytes, detargeting, gene transfer, lentiviral vector, miRNA, targeting.
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Published on: 10 September, 2013
Page: [1336 - 1346]