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Evaluation of delivery conditions for cutaneous plasmid electrotransfer using a multielectrode array

Abstract

Electroporation (EP) is a simple in vivo method to deliver normally impermeable molecules, such as plasmid DNA, to a variety of tissues. Delivery of plasmid DNA by EP to a large surface area is not practical because the distance between the electrode pairs, and therefore the applied voltage, must be increased to effectively permeabilize the cell membrane. The design of the multielectrode array (MEA) incorporates multiple electrode pairs at a fixed distance to allow for delivery of plasmid DNA to the skin, potentially reducing the sensation associated with in vivo EP. In this report, we evaluate the effects of field strength and pulse width on transgene expression and duration using a plasmid encoding the luciferase reporter gene delivered by intradermal injection in a guinea pig model followed by EP with the MEA. As expected, the level of luciferase expression increased with the magnitude and duration of the voltage applied. In addition to adjusting transgene expression levels by altering fielding strength, levels could also be controlled by adjusting the plasmid dose. Our results indicate that the design of the MEA is a viable option for cutaneous plasmid DNA delivery by in vivo EP to a large surface area.

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Acknowledgements

This research was supported in part by a research grant from the National Institutes of Health R01 EB005441 and by the Frank Reidy Research Center for Bioelectrics at Old Dominion University. We thank Dr Mark Jaroszeski (University of South Florida) for construction of the multielectrode array.

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Correspondence to R Heller.

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With respect to duality of interest and financial disclosures, Dr R Heller is an inventor on patents, which cover the technology that was used in the work reported in this paper. One or more of the patents have been licensed to Inovio Pharmaceutical Corp. In addition, Dr R Heller owns stock and stock options in Inovio and has an ownership interest in RMR Technologies.

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Ferraro, B., Heller, L., Cruz, Y. et al. Evaluation of delivery conditions for cutaneous plasmid electrotransfer using a multielectrode array. Gene Ther 18, 496–500 (2011). https://doi.org/10.1038/gt.2010.171

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