Topical Gene Electrotransfer to the Epidermis of Hairless Guinea Pig by Non-invasive Multielectrode Array

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 geneelectrotransfer with the MEA, although a significant increase of Factor IX was obtained in the skin of animals. These results suggest geneelectrotransfer 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

Topical gene electrotransfer to the epidermis of hairless guinea pig by non-invasive multielectrode array.

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

Body weight increase of HLGP after i.d. DNA injection and non-invasive GET.

<p>Delivery group, IO: 50 µL DNA without pulse delivery; GET: 50 µL DNA with 1 pulse delivery on the injection site; 4GET: 4 injections with 50 µL DNA and each pulse delivery on the injection site. Bars represent mean ± SD. 4 animals were analyzed for each delivery group. * p<0.05 for 4GET or GET vs IO by One Way RM-ANOVA.</p

Gross observation and histology of HLGP skin after i.d. DNA injection and non-invasive GET.

<p><b>A</b>, Skin observation after delivery. Pictures were taken at post-delivery day 1, day 5 and day 8. One representative picture of 4 to 6 sites was shown here. Delivery group, IO: 50 µL DNA without pulse delivery; GET: 50 µL DNA with pulse delivery. <b>B</b>, H&E stained skin samples. One representative of 3 treated sites was presented here for post-delivery day 2 or day 7 (magnification  = 200, scale bar = 100 µm).</p