Polyelectrolyte multilayer-mediated gene delivery for semaphorin signaling pathway control.
Fiche publication
Date publication
novembre 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAGNARD Dominique, Dr VOEGEL Jean-Claude, Pr SCHAAF Pierre
Tous les auteurs :
Richard D, Nguyen I, Affolter C, Meyer F, Schaaf P, Voegel JC, Bagnard D, Ogier J
Lien Pubmed
Résumé
The capability of multilayered polyelectrolyte films (MPFs) to control the sequential expression of two genes encoding cell receptors involved in a common cell signalling activity is shown, while achieving a fully functional signal transduction. As a functional model system representative of a cell signalling process that proceeds in a top-down manner, cell collapse induced by semaphorin 3A (Sema3A) was chosen as the target. Polyelectrolyte multilayers were sequentially functionalized with two plasmids encoding Neuropilin-1 (NRP-1) and Plexin-A1 (Plx-A1), respectively, acting as co-receptors for Sema3A. By using hyaluronan and chitosan as structural components for the incorporation of plasmid DNA layers onto precursor films made of poly-allylamine hydrochloride and poly-sodium-4-styrenesulfonate, the polyelectrolyte system is established; this systems is capable of delivering both plasmids to Cos-1 cells in a manner that permits control over the timing and the respective order in which the two plasmid DNA constructs are expressed. Importantly, it was observed that, following Sema3A stimulation, COS-1 cells co-expressing Plx-A1 and NRP-1 display a collapse phenotype, which is determined by the multilayer build-up scheme, and that the expression products of both transgenes embedded in MPFs are temporally functional over several days while acting their role of co-receptors for Sema3A.
Référence
Small. 2010 Nov 5;6(21):2405-11.