DNA Delivery with Electroporation

The potential for DNA vaccines in the treatment and prevention of cancer has gained great momentum since initial findings almost 2 decades ago that revealed that genetically engineered DNA can elicit an immune response. The combination of adjuvants and an effective delivery method such as electroporation is overcoming past setbacks for naked plasmid DNA (pDNA) as a potential preventive or therapeutic approach to cancer in large animals and humans.

How Does EP Work
To date, numerous delivery methods have been investigated to boost efficacy of non-viral gene therapies such as lipid-mediated entry into cells, jet injection, gene gun delivery, and sonoporation. Although the exact mechanism of cellular macromolecule entry is still under discussion, entry of small molecules such as anticancer therapeutics seems to occur by simple diffusion after the pulse, and larger molecules such as pDNA are thought to enter through a multistep mechanism involving the interaction of the DNA molecule with the destabilized membrane during the pulse and then its passage across the membrane. The cell membrane then reseals and the cellular machinery uses the DNA code to produce the desired antigen. Antigen-presenting cells then engulf the produced antigen and transport them to the lymph nodes where the antibodies or T cells are produced to eliminate the cancerous cells.

The Effectiveness of EP as A Delivery Method for DNA Vaccines
Numerous preclinical studies have examined the effectiveness of EP as a delivery method for DNA vaccines. EP appears to have a great impact on immunogenicity and efficacy by increasing antigen delivery up to a 1000-fold over naked DNA delivery alone. The effectiveness of the delivery method of EP has been shown to improve antitumor immune responses when used in a prime/boost strategy. Different procedures of DNA vaccine delivery, namely intradermal injection, gene gun delivery, and intramuscular injection alone or with EP, were compared in a murine transgenic model of mammary carcinoma overexpressing HER2/neu. In this study, intramuscular delivery followed by EP elicited better protection against HER2/neu spontaneous tumor development and induced an immune response.

Overall, EP has been shown to be an efficient method for enhancing the uptake and expression of DNA vaccine candidates, enabling the use of a lower dose of vaccine with similar or higher efficacy. Optimization of EP will also increase its acceptability as a delivery method by potentially reducing the associated pain with the procedure. The current of intradermal vaccination by EP impacts antigen expression, inflammation, and the induction of both humoral and cellular immunity. In general, the delivery of DNA vaccines via either intramuscular, intratumoral, or intradermal EP has been proven to enhance antigen-specific antibody and cellular immunity compared to delivery to tissue alone.