Increases in efficiency have made naked DNA gene transfer a viable method for gene therapy. Intravascular delivery results in effective gene delivery to liver and muscle, and provides in vivo transfection methods for basic and applied gene therapy and antisense strategies with oligonucleotides and small interfering RNA (siRNA). Delivery via the tail vein in rodents provides an especially simple and effective means for in vivo gene transfer. Electroporation methods significantly enhance direct injection of naked DNA for genetic immunization. The availability of plasmid DNA expression vectors that enable sustained high level expression, allows for the development of gene therapies based on the delivery of naked plasmid DNA.