Nonviral skin gene therapy.
Nonviral skin gene therapy is an effective method to directly deliver and transiently express genes in the skin. Several different nonviral delivery methods have been successfully used and are analyzed here for their efficiency and efficacy in achieving specific therapeutic applications. For one important and frequently used application of nonviral skin gene therapy, genetic immunization, the types of resulting immune responses (Th1 versus Th2) will depend on which delivery method is used. In addition, we discuss the contributions of DNA as an immunostimulatory adjuvant in genetic immunization and how activation of skin dendritic cells and induction of IL-12 expression are mechanistically important in this process. Nonviral skin gene therapy has also been successfully used to enhance tumor regression in animal models, frequently by inducing a specific immune response against the tumor. In the future, nonviral skin gene therapy may be successfully used for the treatment of additional skin diseases if genes can be selectively delivered and expressed in specific skin cells, and if increased level and duration of gene expression can be achieved.
Vogel
J C
JC
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. jonvogel@box-j-nih.gov
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D004247:DNA