Abstract
With the first demonstration in the early 1990s that plasmid DNA could be taken up by somatic cells in vivo, resulting in expression of genes encoded by the plasmid and controlled by mammalian promoters, the stage was set for the investigation of the range of compelling applications for endogenous expression of proteins in animals and humans [1]. The finding that simple injection of purified plasmid DNA into a target tissue could induce sustained endogenous production of proteins from the recipient’s own cells precipitated a flurry of research that was hoped would quickly lead to therapies for genetic, metabolic, and infectious diseases, as well as cancer. Unfortunately, while the past two decades have seen substantial progress in understanding the advantages and limitations of nucleic acid-based interventions for human disease as well as licensure of multiple veterinary products, there are currently no DNA-based products approved for human use. With well over 100 human clinical studies of DNA-based product candidates conducted to date, the overarching conclusion from these studies is that, for the vast majority of applications, conventional injection of plasmid DNA into tissues at clinically feasible dose levels is unable to produce consistent, biologically meaningful responses, especially when scaled up from rodent models into larger animal species (including humans) [2]. One key factor contributing to these results is the relatively low efficiency with which DNA crosses the cell membrane to reach its intracellular site of action [3]. To address this issue, many approaches for improving the intracellular uptake of DNA have been evaluated, with electroporation-mediated DNA delivery being one of the most promising. This chapter will discuss the utility of DNA vaccines, and the promise that electroporation delivery systems bring to the use of nucleic acid-based vaccine strategies, as well as the potential impact of electroporation on the field of vaccines in general.
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References
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Evans, C.F., Hannaman, D. (2013). Current Status of Electroporation Technologies for Vaccine Delivery. In: Singh, M. (eds) Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-5380-2_9
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