Electrotransfer Parameters As a Tool for Controlled and Targeted Gene Expression in Skin

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2016 Aug 31

PMID 27574782

Citations 16

Authors

Spela Kos

Tanja Blagus

Maja Cemazar

Ursa Lampreht Tratar

Monika Stimac

Lara Prosen

Tanja Dolinsek

Urska Kamensek

Simona Kranjc

Lars Steinstraesser

Gaelle Vandermeulen

Veronique Preat

Gregor Sersa

Affiliations

Soon will be listed here.

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.

Citing Articles

In Vivo Wound Healing Model for Characterization of Gene Electrotransfer Effects in Mouse Skin.

Kos S, Jesenko T, Blagus T Methods Mol Biol. 2024; 2773:87-96.

PMID: 38236539 DOI: 10.1007/978-1-0716-3714-2_9.

What We Learned about the Feasibility of Gene Electrotransfer for Vaccination on a Model of COVID-19 Vaccine.

Kamensek U, Cemazar M, Brezar S, Jesenko T, Kos S, Znidar K Pharmaceutics. 2023; 15(7).

PMID: 37514166 PMC: 10385748. DOI: 10.3390/pharmaceutics15071981.

The effectiveness of calcium electroporation combined with gene electrotransfer of a plasmid encoding IL-12 is tumor type-dependent.

Lisec B, Markelc B, Ursic Valentinuzzi K, Sersa G, Cemazar M Front Immunol. 2023; 14:1189960.

PMID: 37304301 PMC: 10247961. DOI: 10.3389/fimmu.2023.1189960.

Design, Development, and Testing of a Device for Gene Electrotransfer to Skin Cells In Vivo.

Cvetkoska A, Dermol-Cerne J, Miklavcic D, Brezar S, Markelc B, Sersa G Pharmaceutics. 2022; 14(9).

PMID: 36145573 PMC: 9505516. DOI: 10.3390/pharmaceutics14091826.

In vitro and in vivo correlation of skin and cellular responses to nucleic acid delivery.

Bosnjak M, Znidar K, Sales Conniff A, Jesenko T, Markelc B, Semenova N Biomed Pharmacother. 2022; 150:113088.

PMID: 35658241 PMC: 10010056. DOI: 10.1016/j.biopha.2022.113088.

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