Puncture-Mediated Gene Transfer to the Skin

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Abstract
Simple and efficient gene transfer to the skin would facilitate many local and systemic gene therapy applications. Here we report a novel approach that allows installation and expression of plasmid DNA without a particulate carrier into the skin for the purposes of gene therapy. A device with a constantly high-frequency oscillating bundle of fine metal needles allows puncturing of the skin and leads to DNA transfer to skin-associated cells and expression of reporter genes in mice. Furthermore, puncture-mediated instillation of an expression vector coding for a single T cell epitope induces specific cellular immune responses. If this approach could be optimized, puncture-mediated gene transfer might be useful for the treatment of large body areas with plasmid DNA for the purpose of somatic gene therapy. Somatic gene therapy with naked DNA is a potentially important approach to skin disorders and for the expression of genes with systemic effects. We report an novel approach related to tattooing that allows DNA to be efficiently introduced into the skin without a particulate carrier. Puncture-mediated gene transfer could allow homogeneous treatment of large body surface areas for gene replacement therapy.