Essential hypertension, defined as high blood pressure with no identifiable cause, affecting 95% of hypertensive patients. It is considered to be the consequence of an interaction between environmental and genetic factors. Hitherto, many candidate genes in the renin-angiotensin-aldosterone system, the sympathetic nervous system, and water-sodium balance system have been widely studied. Among all these genes which play important roles in the etiology of hypertension, those encoding the main components of the RAAS are deemed the most possible candidate genes since the RAAS plays a fundamental role in the maintenance of blood pressure and cardiovascular homeostasis. Epidermal gene transfer is suggested as a new therapeutic strategy for a variety of skin diseases, vaccination and systemic disorders. Long-term or persistent gene delivery to the epidermis has promise for inherited skin diseases and potentially systemic disorders. Topical application of plasmid DNA results in low levels and short duration of gene expression in epidermal skin. Cutaneous gene electrotransfer following intradermal DNA injection has been widely studied. The level and duration of gene expression is quite different, depending on which type of electrodes and which species of animals was utilized. However, definitive epidermal expression by GET in guinea pig or human skin xenograft mouse model has been demonstrated by only a few groups of researchers. The human skin xenograft mouse model may be the best choice for preclinical skin research. However, sources of human skin are very limited. A second option is hairless guinea 
pig skin, whose skin is very similar to human skin anatomically and histologically as opposed to the skin of normal rodents. Previously, we demonstrated that GET to the skin resulted in efficient expression in rat and the Hartley guinea pig. In this study, we further characterize several important aspects associated with potential clinical applications, such as the level and duration of gene expression, distribution of gene expression within the tissue and side effects in this model. We also investigated if a therapeutic protein, human factor IX, could be expressed in the skin following delivery using the non-invasive MEA and whether it could reach the blood circulation. The xenograft human skin-SCID chimera has been reported as a valuable model for pathological research of several skin disorders including psoriasis, cutaneous lupus, pemphigus, vitiligo and androgenetic alopecia. However, the immune deficiency of the xenograft model limits its application for immunomodulation, including vaccination and immune therapy for skin cancer. A few skin electrotransfer studies have been performed in rabbit or pig skin, while most studies of skin GET have been performed in mouse or rat skin, which is significantly different from human skin.