Plasmids used in DNA Vaccines produce proteins that produce an immune response. Some of the earliest experiments conducted in the late 1980’s and early 1990’s demonstrated DNA uptake and gene expression by cells in regenerating muscle tissue of rodents.These experiments allowed for the term “naked DNA” to be coined by Vical in San Diego, Ca. Naked DNA refers to DNA delivered free from agents which promote transfection. Delivered in vivo, DNA vaccine plasmids continue to prove to be immunogenic in humans and animals. There are several advantages of using plasmid DNA encoding proteins in DNA vaccines such as: 1. The effective intracellular translation of these proteins to the processing pathways that generate the fragments needed to induce cellular immune responses, specifically T-cell responses. 2. The ease of DNA plasmid manufacturing using E. coli versus the manufacturing of vaccines in eggs. 3. The stability of a DNA plasmid. 4. The lack of pre-existing immunity in vaccine recipients which might limit DNA uptake. There were initial concerns with the possibility that vaccine DNA could be integrated into the recipient’s genome, and potentially cause cancer. These concerns were shown to be untrue through a series of experiments completed in the mid-to-late 1990s, which has since cleared the path for clinical testing. More recently the use of polymers and cationic lipid-based materials to increase the transfection efficiency into cells has also received significant attention from researchers. At this time two of the most advanced transfection-enhancing materials are being developed by Vical. Phase I and II clinical testing of their products have been completed and yielded promising results in terms of safety and immunogenicity. In terms of DNA vaccine delivery, the use of three devices to increase plasmid uptake or to target either the skin or muscle cells are becoming increasingly popular. 1. A technology known as the gene gun owned by Pfizer, delivers the vaccine adsorbed by microscopic gold particles to the skin. 2. Using gas pressure, a needle-free injection device by Bioject Inc. delivers the vaccine to either the skin or muscle. 3. In vivo electroporation devices being developed by Inovio Pharmaceuticals and Ichor Medical Systems deliver the vaccines to either the skin or muscle. The DNA vacine industry with the use of new technology for delivery holds promising cures for our future.