Historically, Wolff and colleagues [4] first demonstrated that long-term gene expression in mouse skeletal muscle could be achieved with direct intramuscular injection of 2 Journal of Biomedicine and Biotechnology plasmid DNA. This and other early studies, demonstrating the feasibility of direct intramuscular gene transfer for DNA vaccination purpose, propelled the first vaccination studies utilizing plasmid DNA in protection scenarios involving influenza [5] and HIV-1 [6] . Cellular and humoral immune responses have been demonstrated after the injection of naked plasmid DNA vaccines into the dermis or muscle tissue of mice [5, 7] . Such responses have induced protection in preclinical models of infectious disease and malignancies (for review, see Donnelly et al. [8] ).