The long-range goal of this research program is the development of efficient in vivo gene delivery systems. The goal of this project is the development of an improved electroporation system for the delivery of plasmid DNA to the skin. Critical elements for such a system are reproducibility, portability and the ability to perform multiple applications to the same subject. In vivo electroporation has been shown to be an effective way of enhancing delivery of plasmid DNA. The skin is an attractive target for gene therapy protocols for cutaneous diseases, vaccines and several metabolic disorders because it is easily accessible for both delivery and monitoring. A critical consideration for successful delivery of electrically mediated delivery to the skin is the applicator used to apply the electric pulses. The applicator should treat a sufficient area and be flexible to assure good contact with the tissue. This study is designed to develop and to demonstrate that a tissue conformable electroporation applicator can be used to efficiently deliver plasmid DNA. To accomplish this goal the following three specific aims will be performed: i. to evaluate a new conformable electrode array designed for delivery of plasmid DNA to the skin, to establish delivery parameters for maximal expression and to determine the relationship between the total area treated and the level of expression; ii. to configure and test a conformable skin applicator containing microneedles for plasmid DNA delivery based on the electrical parameters established in Specific Aim i; and iii. to determine if the system established in the first two Specific Aims can deliver plasmids coding for proteins applicable for therapeutic purposes, to determine the duration of maximal expression levels and to determine if this time can be increased by performing multiple delivery procedures. The work will be performed in hairless guinea pigs. Initially, the optimal electroporation conditions to maximize DNA delivery and expression will be determined. This work will also establish the relationship between the size of the treated area and expression levels. This information will help establish an effective way to deliver naked DNA to the skin. The investigators have pioneered the use of electroporation for in vivo delivery so are well suited to successfully complete the study. ? ? ?

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Henderson, Lori
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University of South Florida
Schools of Medicine
United States
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Donate, Amy; Heller, Richard (2013) Assessment of delivery parameters with the multi-electrode array for development of a DNA vaccine against Bacillus anthracis. Bioelectrochemistry 94:1-6
Guo, Siqi; Israel, Annelise L; Basu, Gaurav et al. (2013) Topical gene electrotransfer to the epidermis of hairless guinea pig by non-invasive multielectrode array. PLoS One 8:e73423
Guo, Siqi; Donate, Amy; Basu, Gaurav et al. (2011) Electro-gene transfer to skin using a noninvasive multielectrode array. J Control Release 151:256-62
Heller, Richard; Shirley, Shawna; Guo, Siqi et al. (2011) Electroporation based gene therapy--from the bench to the bedside. Conf Proc IEEE Eng Med Biol Soc 2011:736-8
Donate, Amy; Coppola, Domenico; Cruz, Yolmari et al. (2011) Evaluation of a novel non-penetrating electrode for use in DNA vaccination. PLoS One 6:e19181
Ferraro, B; Heller, L C; Cruz, Y L et al. (2011) Evaluation of delivery conditions for cutaneous plasmid electrotransfer using a multielectrode array. Gene Ther 18:496-500
Ferraro, B; Cruz, Y L; Baldwin, M et al. (2010) Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation. Gene Ther 17:763-9
Heller, Richard; Cruz, Yolmari; Heller, Loree C et al. (2010) Electrically mediated delivery of plasmid DNA to the skin, using a multielectrode array. Hum Gene Ther 21:357-62
Ferraro, Bernadette; Cruz, Yolmari L; Coppola, Domenico et al. (2009) Intradermal delivery of plasmid VEGF(165) by electroporation promotes wound healing. Mol Ther 17:651-7
Heller, Loree C; Jaroszeski, Mark J; Coppola, Domenico et al. (2008) Comparison of electrically mediated and liposome-complexed plasmid DNA delivery to the skin. Genet Vaccines Ther 6:16

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