期刊
JOURNAL OF CONTROLLED RELEASE
卷 151, 期 3, 页码 256-262出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.01.014
关键词
Electroporation; Gene delivery; Guinea pig; Skin; Multielectrode array
资金
- National Institutes of Health [R01 EB005441]
- Frank Reidy Research Center for Bioelectrics at Old Dominion University
Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications. (C) 2011 Elsevier B.V. All rights reserved.
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