Nonviral skin gene therapy is an effective method to directly deliver and t
ransiently express genes in the skin. Several different nonviral delivery m
ethods have been successfully used and are analyzed here for their efficien
cy and efficacy in achieving specific therapeutic applications. For one imp
ortant and frequently used application of nonviral skin gene therapy, genet
ic immunization, the types of resulting immune responses (Th1 versus Th2) w
ill depend on which delivery method is used. In addition, we discuss the co
ntributions of DNA as an immunostimulatory adjuvant in genetic immunization
and how activation of skin dendritic cells and induction of IL-12 expressi
on are mechanistically important in this process. Nonviral skin gene therap
y has also been successfully used to enhance tumor regression in animal mod
els, frequently by inducing a specific immune response against the tumor. I
n the future, nonviral skin gene therapy may be successfully used for the t
reatment of additional skin diseases if genes can be selectively delivered
and expressed in specific skin cells, and if increased level and duration o
f gene expression can be achieved.