EXPRESSION OF NAKED DNA IN HUMAN, PIG, AND MOUSE SKIN

The insertion and expression of genes in the epidermis may have a vari ety of therapeutic uses, including the treatment of skin diseases. Her e we show that when both human skin organ cultures and human skin graf ts on immunocompromised mice are injected with naked DNA, the DNA is t aken-up and genes are expressed in the epidermis in a manner similar t o both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in th e epidermis, but also in the dermis and underlying fat and muscle tiss ue, and is expressed at lower levels, These findings suggest that gene s can be expressed in human skin, after injection of naked DNA, and in dicate that pig skin is an appropriate model for the study of DNA upta ke and gene expression in human skin, The organ cultures of human and pig skin may be useful in understanding how naked DNA is internalized and expressed after in vivo injections. Additionally, skin obtained fr om patients with skin disease maybe studied as skin grafts and organ c ultures to help optimize genetic approaches for the treatment of skin diseases prior to clinical trials, by determining if the injected gene can provide a therapeutic benefit.