title: Inhibition of Sox2 Expression in the Adult Neural Stem Cell Niche In Vivo by Monocationic-based siRNA Delivery.
abstract: RNA interference (RNAi) is a major tool for basic and applied investigations. However, obtaining RNAi data that have physiological significance requires investigation of regulations and therapeutic strategies in appropriate in vivo settings. To examine in vivo gene regulation and protein function in the adult neural stem cell (NSC) niche, we optimized a new non-viral vector for delivery of siRNA into the subventricular zone (SVZ). This brain region contains the neural stem and progenitor cells populations that express the stem cell marker, SOX2. Temporally and spatially controlled Sox2 knockdown was achieved using the monocationic lipid vector, IC10. siRNA/IC10 complexes were stable over time and smaller (<40 nm) than jetSi complexes (≈400 nm). Immunocytochemistry showed that siRNA/IC10 complexes efficiently target both the progenitor and stem cell populations in the adult SVZ. Injection of the complexes into the lateral brain ventricle resulted in specific knockdown of Sox2 in the SVZ. Furthermore, IC10-mediated transient in vivo knockdown of Sox2-modulated expression of several genes implicated in NSC maintenance. Taken together, these data show that IC10 cationic lipid formulation can efficiently vectorize siRNA in a specific area of the adult mouse brain, achieving spatially and temporally defined loss of function.Molecular Therapy-Nucleic Acids (2013) 2, e89; doi:10.1038/mtna.2013.8; published online 23 April 2013.
authors.affiliation: Laboratoire d'Evolution des Régulations Endocriniennes, MNHN, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Remaud
authors.forename: Silvia Alejandra
authors.initials: SA
authors.lastname: López-Juárez
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bolcato-Bellemin
authors.forename: Patrick
authors.initials: P
authors.lastname: Neuberg
authors.forename: Fabrice
authors.initials: F
authors.lastname: Stock
authors.forename: Marie-Elise
authors.initials: ME
authors.lastname: Bonnet
authors.forename: Rym
authors.initials: R
authors.lastname: Ghaddab
authors.forename: Marie Stéphanie
authors.initials: MS
authors.lastname: Clerget-Froidevaux
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Pierre-Simons
authors.forename: Patrick
authors.initials: P
authors.lastname: Erbacher
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Demeneix
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Morvan-Dubois