Monopolar Gene Electrotransfer Enhances Plasmid DNA Delivery to Skin

Authors

Anna Bulysheva, Old Dominion UniversityFollow
Loree Heller
Michael Francis
Frency Varghese
Carly Boye
Richard Heller

Document Type

Article

Publication Date

2021

DOI

10.1016/j.bioelechem.2021.107814

Publication Title

Bioelectrochemistry

Volume

140

Pages

107814-107819

Abstract

A novel monopolar electroporation system and methodologies were developed for in vivo electroporation intended for potential clinical applications such as gene therapy. We hypothesized that an asymmetric anode/cathode electrode applicator geometry could produce favorable electric fields for electroporation, without the typical drawback associated with traditional needle and parallel plate geometries. Three monopolar electrode applicator prototypes were built and tested for gene delivery of reporter genes to the skin in a guinea pig model. Gene expression was evaluated in terms of kinetics over time and expression distribution within the treatment site. Different pulsing parameters, including pulse amplitude, pulse duration, and pulse number were evaluated. Monopolar gene electrotransfer significantly enhanced gene expression compared to controls over the course of 21 days. Gene expression distribution was observed throughout the full thickness of the epidermis, as well as notable expression in the deeper layers of the skin, including the dermis, and the underlying striated muscle without any damage at the treatment site, which is a substantial improvement over previously reported expression confined to the epidermis only. Expression distribution observed is consistent with the electric field distribution model, indicating that our novel electrode geometry results in targeted electroporation and gene transfer. This is important, as it may facilitate translation of many electroporation-based clinical therapies including gene therapies, IRE, and ECT.

Comments

© 2021 The Authors

Published under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

Original Publication Citation

Bulysheva, A., Heller, L., Francis, M., Varghese, F., Boye, C., & Heller, R. (2021). Monopolar gene electrotransfer enhances plasmid DNA delivery to skin. Bioelectrochemistry, 140, 107814-107819, Article 107814. https://doi.org/10.1016/j.bioelechem.2021.107814

Repository Citation

Bulysheva, Anna; Heller, Loree; Francis, Michael; Varghese, Frency; Boye, Carly; and Heller, Richard, "Monopolar Gene Electrotransfer Enhances Plasmid DNA Delivery to Skin" (2021). Electrical & Computer Engineering Faculty Publications. 278.
https://digitalcommons.odu.edu/ece_fac_pubs/278