Safety and pharmacokinetics of naked plasmid DNA in the skin: Studies on dissemination and ectopic expression

Gene therapy using naked DNA injected into muscle and skin is increasingly being used for vaccination and treatment purposes. Favorably, naked plasmid DNA does not exhibit the various limitations inherent to viral vectors, su ch as the elicitation of adverse immune responses and the risk of insertion al mutagenesis. In order to assess the distribution and safety of naked pla smid DNA in a relevant animal model, we analyzed if intracutaneously inject ed plasmid DNA was transported to other organs and if ectopic expression oc curred. When a "superdose" of a marker plasmid was injected intradermally, most organs were found transiently to contain the plasmid DNA for several d ays, whereas integration into the host genome was not detected. With the ex ception of ovary, however, mRNA expression only occurred in the skin, regio nal lymph nodes, and muscular tissues. From a safety standpoint, skin gene therapy with naked plasmid DNA can be considered safe due to the rapid biod egradation of plasmid DNA and the exclusive and transient expression of for eign genes in tissues known to take up DNA.