title: Lentiviral vectors: a powerful tool to target astrocytes in vivo.
abstract: 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.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Delzor
authors.affiliation: Centre Hospitalier Universitaire Vaudois (CHUV), Département des Neurosciences Cliniques (DNC), Laboratoire de Neurothérapies Cellulaires et Moléculaires (LNCM), Avenue de Beaumont, Pavillon 3, 1011 Lausanne, Switzerland. nicole.deglon@chuv.ch.
authors.forename: Delzor
authors.initials: D
authors.lastname: Aurélie
authors.forename: Carole
authors.initials: C
authors.lastname: Escartin
authors.forename: Escartin
authors.initials: E
authors.lastname: Carole
authors.forename: Nicole
authors.initials: N
authors.lastname: Déglon
authors.forename: Déglon
authors.initials: D
authors.lastname: Nicole
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000503:physiopathology / Q000628:therapy; D005786:Gene Expression Regulation; D018390:Gene Targeting / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D014161:Transduction, Genetic; D019076:Transgenes; D056189:Viral Tropism; D053586:Virus Internalization
chemical_list: D035683:MicroRNAs