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Skin-targeted gene transfer using in vivo electroporation

Gene Therapy volume 8, pages 1808–1812 (2001)Cite this article

Abstract

The skin is an important target for gene transfer because of its easy accessibility. Using plasmid DNA expressing rat erythropoietin (pCAGGS-Epo) as the vector, we previously demonstrated long-term Epo delivery in rats by muscle-targeted gene transfer using in vivo electroporation. Here we examined whether this electroporation approach could be applied to gene delivery in rat skin. To optimize gene transfer, we tested the efficiency of skin-targeted Epo gene transfer with three types of electrodes at three different electrode voltages. Each rat was injected intradermally with a total of 800 μg of pCAGGS-Epo, in the abdominal area. Plate-and-fork-type electrodes were effective for Epo delivery by skin-targeted gene transfer at low voltages (12~24 V). The vector-derived Epo mRNA was expressed only at the DNA injection site. The Epo gene was expressed in a dose-dependent manner, the expression persisted for 7 weeks, and hematocrit levels were increased for 11 weeks. Skin injection with pCAGGS-lacZ showed lacZ gene expression in the epidermis on day 1 after injection and in the subcutaneous muscle layer on day 7. Slight skin damage due to the gene transfer procedure was evident on day 1, but absent by day 7. These results demonstrate that skin-targeted pCAGGS-Epo transfer by in vivo electroporation at low voltage is a useful procedure for the short-term delivery of Epo.

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Acknowledgements

This work was supported in part by a grant to H Maruyama from the Renal Anemia Foundation (Tokyo). The authors are grateful to K Yamagiwa and N Imai of the Department of Medicine (II), Niigata University School of Medicine, Y Hayakawa of the TR-TECH Co. Ltd, and Y Imada of the Unique Medical Imada Co. Ltd, for technical assistance.

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Authors and Affiliations

  1. Department of Medicine (II), Niigata University School of Medicine, Niigata, Japan

    H Maruyama, K Ataka, N Higuchi & F Gejyo

  2. Department of Dermatology, Niigata University School of Medicine, Niigata, Japan

    F Sakamoto

  3. Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Suita, Japan

    J Miyazaki

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  1. H Maruyama
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  2. K Ataka
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  3. N Higuchi
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  4. F Sakamoto
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  5. F Gejyo
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  6. J Miyazaki
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Maruyama, H., Ataka, K., Higuchi, N. et al. Skin-targeted gene transfer using in vivo electroporation. Gene Ther 8, 1808–1812 (2001). https://doi.org/10.1038/sj.gt.3301604

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  • DOI: https://doi.org/10.1038/sj.gt.3301604

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