Gene transfer engineering for astrocyte-specific silencing in the CNS.

Détails

Ressource 1Télécharger: 5_26109254_LPostprint.pdf (3196.13 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_FDB9E827C4A3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Gene transfer engineering for astrocyte-specific silencing in the CNS.
Périodique
Gene Therapy
Auteur(s)
Merienne N., Delzor A., Viret A., Dufour N., Rey M., Hantraye P., Déglon N.
ISSN
1476-5462 (Electronic)
ISSN-L
0969-7128
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
22
Numéro
10
Pages
830-839
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Cell-type-specific gene silencing is critical to understand cell functions in normal and pathological conditions, in particular in the brain where strong cellular heterogeneity exists. Molecular engineering of lentiviral vectors has been widely used to express genes of interest specifically in neurons or astrocytes. However, we show that these strategies are not suitable for astrocyte-specific gene silencing due to the processing of small hairpin RNA (shRNA) in a cell. Here we develop an indirect method based on a tetracycline-regulated system to fully restrict shRNA expression to astrocytes. The combination of Mokola-G envelope pseudotyping, glutamine synthetase promoter and two distinct microRNA target sequences provides a powerful tool for efficient and cell-type-specific gene silencing in the central nervous system. We anticipate our vector will be a potent and versatile system to improve the targeting of cell populations for fundamental as well as therapeutic applications.
Mots-clé
Animals, Astrocytes/physiology, Central Nervous System/cytology, Central Nervous System/physiology, Gene Expression Regulation, Gene Silencing, Gene Transfer Techniques, Genetic Vectors, Lentivirus, Mice, Mice, Transgenic, RNA, Small Interfering, Tetracycline
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/10/2015 10:35
Dernière modification de la notice
20/08/2019 16:28
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