title: Electrotransfer parameters as a tool for controlled and targeted gene expression in skin.
abstract: Skin is an attractive target for gene electrotransfer. It consists of different cell types that can be transfected, leading to various responses to gene electrotransfer. We demonstrate that these responses could be controlled by selecting the appropriate electrotransfer parameters. Specifically, the application of low or high electric pulses, applied by multi-electrode array, provided the possibility to control the depth of the transfection in the skin, the duration and the level of gene expression, as well as the local or systemic distribution of the transgene. The influence of electric pulse type was first studied using a plasmid encoding a reporter gene (DsRed). Then, plasmids encoding therapeutic genes (IL-12, shRNA against endoglin, shRNA against melanoma cell adhesion molecule) were used, and their effects on wound healing and cutaneous B16F10 melanoma tumors were investigated. The high-voltage pulses resulted in gene expression that was restricted to superficial skin layers and induced a local response. In contrast, the low-voltage electric pulses promoted transfection into the deeper skin layers, resulting in prolonged gene expression and higher transgene production, possibly with systemic distribution. Therefore, in the translation into the clinics, it will be of the utmost importance to adjust the electrotransfer parameters for different therapeutic approaches and specific mode of action of the therapeutic gene.
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Spela
authors: S
authors: Kos
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Tanja
authors: T
authors: Blagus
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.|University of Primorska, Faculty of Health Sciences, Izola, Slovenia.
authors: Maja
authors: M
authors: Cemazar
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Ursa
authors: U
authors: Lampreht Tratar
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Monika
authors: M
authors: Stimac
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Lara
authors: L
authors: Prosen
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Tanja
authors: T
authors: Dolinsek
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Urska
authors: U
authors: Kamensek
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Simona
authors: S
authors: Kranjc
authors: Department of Plastic Surgery, Burn Center, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors: Lars
authors: L
authors: Steinstraesser
authors: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
authors: Gaëlle
authors: G
authors: Vandermeulen
authors: Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
authors: Véronique
authors: V
authors: Préat
authors: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors: Gregor
authors: G
authors: Sersa