EFFICIENT EXPRESSION OF NAKED PLASMID DNA IN MUCOSAL EPITHELIUM - PROSPECTIVE FOR THE TREATMENT OF SKIN-LESIONS

Mucocutaneous gene therapy offers exciting new treatment modalities fo r skin lesions. Transient expression of naked plasmid DNA could be use d as a local treatment of various skin lesions where the corresponding gene product (protein) has therapeutic or immunization potential. We analyzed the time course, magnitude, and histologic expression of the indicator plasmid DNA (pCMV:beta-Gal) in mucosal epithelium and papill oma lesions. Upon direct injection of naked plasmid DNA (20 mu g) into oral mucosa, expression occurred at high local concentrations, up to 35-fold higher than in comparable injections into the epidermis, Due t o the accelerated turnover of mucosal epithelium beta-galactosidase po sitive epithelial cells were detected in the basal and suprabasal laye rs as early as 3 h after injection, whereas only the most superficial mucosal layers demonstrated beta-galactosidase staining at 24 h post-i njection. These biologic characteristics need to be taken into conside ration when clinical applications of expressing naked plasmid DNA in e pithelial tissues are considered.