Abstract: Skin cells are genetically altered to express a gene product encoded by an introduced polynucleotide. Specifically, the invention involves introduction of a nucleotide of interest into a skin cell by topical application of a polynucleotide that is substantially free of liposomes or charged lipids, where the skin can be either treated or untreated prior to application. Similarly, the invention involves introduction of a nucleotide of interest into a skin cell by topical application of a polynucleotide formulation comprising a liposome or charged lipid, wherein the skin is not treated by removal of hair prior to application. The method of the invention serves as a platform for delivering polynucleotides to skin cells for expression therein for any of a variety uses including, but not limited to genetic immunization.