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Electroporation-mediated gene transfer directly to the swine heart

Gene Therapy volume 20, pages 151–157 (2013)Cite this article

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Abstract

In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease. In the current study, we investigated the use of in vivo electroporation for gene transfer using three different penetrating electrodes and one non-penetrating electrode. The hearts of adult male swine were exposed through a sternotomy. Eight electric pulses synchronized to the rising phase of the R wave of the electrocardiogram were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein. Four sites on the anterior wall of the left ventricle were treated. Animals were killed 48 h after injection and electroporation and gene expression was determined. Results were compared with sites in the heart that received plasmid injection but no electric pulses or were not treated. Gene expression was higher in all electroporated sites when compared with injection only sites demonstrating the robustness of this approach. Our results provide evidence that in vivo electroporation can be a safe and effective non-viral method for delivering genes to the heart, in vivo.

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Acknowledgements

This research was supported in part by a research grant from the National Institutes of Health R21 HL005441 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 electrode arrays.

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Authors and Affiliations

  1. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA

    B Hargrave, H Downey, C Lundberg, A Israel, Y-J Chen & R Heller

  2. College of Sciences, Old Dominion University, Norfolk, VA, USA

    B Hargrave

  3. Naval Medical Center Portsmouth, Portsmouth, VA, USA

    R Strange Jr & C Cinnamond

  4. Sobran, Fairfax, VA, USA

    L Murray

  5. College of Medicine, University of South Florida, Tampa, FL, USA

    W Marshall Jr

  6. College of Health Sciences, Old Dominion University, Norfolk, VA, USA

    R Heller

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  1. B Hargrave
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  7. A Israel
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Correspondence to R Heller.

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Competing interests

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. In addition, Dr R Heller owns stock and stock options in Inovio Pharmaceutical Corp.

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Some of the authors of in this paper are employees of the United States Government and the United States Navy. The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense or the United States Government.

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Hargrave, B., Downey, H., Strange, R. et al. Electroporation-mediated gene transfer directly to the swine heart. Gene Ther 20, 151–157 (2013). https://doi.org/10.1038/gt.2012.15

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