Delivery of DNA to Skin by Electroporation

The easy accessibility and the large area of the skin make it a potential target for gene therapy (1 ) while its immune activity makes it an efficient site of DNA vaccination (2 ). Despite these potential advantages for the delivery of DNA into the skin, a significant physical barrier impedes the transfer of large molecules, including DNA, into the epidermal cells. First, transdermal transport of molecules is limited by the low permeability of the stratum corneum, the outermost layer of the skin. Only potent lipophilic low molecular-weight (<500) drugs can be delivered by passive diffusion at therapeutic rates. Hence, the transdermal penetration of hydrophilic and/or high molecular-weight molecules, including DNA, requires the use of methods to enhance skin permeability and/or to provide a driving force acting on the permeant. Both chemical (e.g., penetration enhancer) and physical (e.g., iontophoresis, electroporation, or sonophoresis) methods have been used but their efficacy remains low for the transport of macromolecules through the stratum corneum. Besides the stratum corneum, a second barrier to the penetration of DNA in the target cells of the skin is the cell membrane.