This application proposes to explore a novel DNA delivery platform for skin that utilizes topical electrical charge as a mediator of DNA uptake by living cells. This new physical DNA delivery technology differs from other methods in that it does not utilize chemical or biological agents. It differs from other physical DNA delivery methods in that DNA is driven into the skin and delivered to living cells of the skin without the need for an injection, invasive procedures, or skin contact with any device. Preliminary studies indicate that the proposed study will be successful. The overall goal of this R21 study is to characterize and ultimately maximize the effects of topical charge mediated DNA delivery to cells within the skin and to determine if it is feasible to obtain responses that are biologically/clinically relevant. The study aims are designed to: investigate the translocation of plasmid DNA through the skin;determine the effects of charge dose and DNA dose on expression;identify the location of expressing cells and any adverse histological effects in the skin;determine the feasibility of using this technology for vaccination with DNA, and evaluate the potential of this delivery method for inducing therapeutic protein secretion. PUBLIC HEALTH RELEVANCE: This study is relevant to public health as the results may lead to successful DNA based treatments for many types of diseases that require the secretion of a therapeutic protein into the blood. In addition, it may lead to a better means of applying DNA vaccines against infectious diseases.