Plasmid or gene electrotransfer (GET) has been developed in animal models and validated in clinical trials for several indications, primarily cancer therapies and infectious disease vaccines. A complete understanding of the biological responses to GET is important to expanding these fields. After GET, proinflammatory signaling and cell death are detected in vitro; proinflammatory signaling, transient inflammation, and cell death may be observed in vivo. These biological effects may be due to the detection of exogenous nucleic acids by ubiquitously expressed intracellular DNA-specific pattern recognition receptors or DNA sensors. These sensors are universally expressed in mammalian cells; however, DNA sensing, including more than 20 putative, poorly characterized sensors and their interactions, is incompletely understood. The induced biological effects may contribute to therapeutic or vaccine efficacy or may require mitigation. Therefore, it is essential to understand the mechanism of DNA sensing, its signaling pathways, the extent of the biological effects, and their relationship to GET-based therapies.
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