Engineered lentiviral vector targeting astrocytes in vivo.

Détails

ID Serval
serval:BIB_97E9CEF8E732
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Engineered lentiviral vector targeting astrocytes in vivo.
Périodique
Glia
Auteur⸱e⸱s
Colin A., Faideau M., Dufour N., Auregan G., Hassig R., Andrieu T., Brouillet E., Hantraye P., Bonvento G., Déglon N.
ISSN
1098-1136 (Electronic)
ISSN-L
0894-1491
Statut éditorial
Publié
Date de publication
2009
Volume
57
Numéro
6
Pages
667-679
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Astrocytes are involved in key physiological brain processes, such as glutamatergic transmission and energy metabolism, often altered in neurodegenerative diseases. Targeted gene expression in astrocytes is needed to assess the contribution of these cells to physiological processes and for the development of new therapeutic strategies. However, most of the viral vectors currently used for gene transfer in the central nervous system (CNS) are highly neurotropic. We used mokola pseudotyping to shift the tropism of lentiviral vectors toward astrocytes and a detargeting strategy with miRNA to eliminate residual expression in neuronal cells. In primary cultures, we showed that incorporating target sequences for the neuron-specific miR124 effectively abolished transgene expression in neurons post-transcriptionally. Targeted expression of the LacZ reporter gene in astrocytes was achieved in the hippocampus, striatum, and cerebellum of the adult mouse in vivo. As a proof-of-principle, this new lentiviral vector was used to either overexpress or downregulate (RNA interference) the glial glutamate transporter GLAST into striatal astrocytes in vivo. These vectors provide new opportunities for cell type-specific gene transfer in the CNS.
Mots-clé
Amino Acid Transport System X-AG/genetics, Amino Acid Transport System X-AG/metabolism, Animals, Astrocytes/physiology, Cells, Cultured, Cerebellum/physiology, Corpus Striatum/physiology, Gene Expression, Gene Targeting, Gene Transfer Techniques, Genetic Vectors, Hippocampus/physiology, Lac Operon, Lentivirus/genetics, Male, Mice, Mice, Inbred C57BL, MicroRNAs/metabolism, Neurons/physiology, RNA Interference
Pubmed
Web of science
Création de la notice
13/12/2011 16:16
Dernière modification de la notice
20/08/2019 14:59
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