Efficient expression of naked plasmid DNA in mucosal epithelium: prospective for the treatment of skin lesions.

Mucocutaneous gene therapy offers exciting new treatment modalities for skin lesions. Transient expression of naked plasmid DNA could be used 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 papilloma lesions. Upon direct injection of naked plasmid DNA (20 microg) into oral mucosa, expression occurred at high local concentrations, up to 35-fold higher than in comparable injections into the epidermis. Due to the accelerated turnover of mucosal epithelium beta-galactosidase positive epithelial cells were detected in the basal and suprabasal layers as early as 3 h after injection, whereas only the most superficial mucosal layers demonstrated beta-galactosidase staining at 24 h post-injection. These biologic characteristics need to be taken into consideration when clinical applications of expressing naked plasmid DNA in epithelial tissues are considered.