Abstract
Topical gene delivery to the epidermis has the potential to be an effective therapy for skin disorders, cutaneous cancers, vaccinations and systemic metabolic diseases. Previously, we reported on a non-invasive multielectrode array (MEA) that efficiently delivered plasmid DNA and enhanced expression to the skin of several animal models by in vivo gene electrotransfer. Here, we characterized plasmid DNA delivery with the MEA in a hairless guinea pig model, which has a similar histology and structure to human skin. Significant elevation of gene expression up to 4 logs was achieved with intradermal DNA administration followed by topical non-invasive skin gene electrotransfer. This delivery produced gene expression in the skin of hairless guinea pig up to 12 to 15 days. Gene expression was observed exclusively in the epidermis. Skin gene electrotransfer with the MEA resulted in only minimal and mild skin changes. A low level of human Factor IX was detected in the plasma of hairless guinea pig after gene electrotransfer with the MEA, although a significant increase of Factor IX was obtained in the skin of animals. These results suggest gene electrotransfer with the MEA can be a safe, efficient, non-invasive skin delivery method for skin disorders, vaccinations and potential systemic diseases where low levels of gene products are sufficient.
Highlights
Epidermal gene transfer is suggested as a new therapeutic strategy for a variety of skin diseases, vaccination and systemic disorders [1,2,3,4,5]
Because electrogene delivery had not been previously performed in hairless guinea pig skin, we first optimized the delivery condition by adopting the parameters from our previous work in Hartley guinea pigs [12], while testing a wider range of electric fields
All delivery groups with above 50 V showed significantly increased gene expression compared to DNA injection only (p,0.05 for all 3 groups vs DNA injection only), the level of gene expression was no longer enhanced when the applied voltage was further increased up to 70 V
Summary
Epidermal gene transfer is suggested as a new therapeutic strategy for a variety of skin diseases, vaccination and systemic disorders [1,2,3,4,5]. Long-term or persistent gene delivery to the epidermis has promise for inherited skin diseases and potentially systemic disorders [3,5]. Short-term epidermal gene delivery is suitable for vaccination, skin wound or ulcer therapies and skin malignancy [2,3,4,5,6]. Topical application of plasmid DNA results in low levels and short duration of gene expression in epidermal skin [7]. Definitive epidermal expression by GET in guinea pig or human skin xenograft mouse model has been demonstrated by only a few groups of researchers [9,12,15,16]
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