20.500.12556/DiRROS-25285 Between defence and delivery the DNA sensing response to gene electrotransfer Gene therapy has emerged as a transformative biomedical approach, offering new therapeutic possibilities from many so far uncurable diseases through the introduction of recombinant nucleic acids into target cells. Among non-viral delivery techniques, gene electrotransfer (GET) has become one of the frequently applied methods in clinical trials. It is based on the application of short, high-intensity electric pulses that transiently permeabilize cell membranes and enable the efficient transfer of plasmid DNA or other types of recombinant nucleic acids into various cell types. Beyond its role in gene delivery, GET can trigger complex cellular responses, as the introduced DNA interacts with intracellular DNA sensing pathways involved in innate immunity and inflammation. These responses can influence the therapeutic outcome – either by enhancing antitumour and vaccine-related immune activation or by reducing transfection efficiency when excessive inflammation or cell death occur. Our experimental findings in tumour, muscle, and skin models have shown that even non-coding plasmid DNA delivered by GET can induce local immune stimulation and tissue-specific inflammatory signaling, suggesting that the delivered DNA itself contributes to therapeutic efficacy. Conclusions The dual nature of cellular responses following plasmid DNA GET represents both an opportunity and a challenge. Controlled activation of innate immunity can be harnessed to amplify antitumour or vaccine efficacy, while excessive responses may hinder applications requiring cell survival and sustained expression. Understanding these mechanisms enables the rational optimization of GET parameters and plasmid vector design to fully exploit the adjuvant effect or reduce the off-target effect of DNA sensing after GET, based on the desired application. gene electrotransfer DNA sensors gene therapy genski elektroprenos zaznavanje DNK gensko zdravljenje true false true Association of Radiology and Oncology Ljubljana Angleški jezik Slovenski jezik by Authors Neznano 2026-01-15 03:47:54 2026-01-16 14:45:27 2026-01-17 04:06:01 0000-00-00 00:00:00 2025 0 Ljubljana 0 str. 467-476 no. 4 Vol. 59 Dec. 2025 0000-00-00 Zaloznikova Objavljeno apc 2025-11-10 2025-11-17 2025-12-01 602.6/.7 1318-2099 10.2478/raon-2025-0063 262914819 RAZ_Jesenko_Tanja_2025.pdf RAZ_Jesenko_Tanja_2025.pdf 1 E7AFF5632694D2B918062935492A7759 04a8af350fc9d3daa9f1110647238b0019a6dfad9a5eddbeaffca9c6bf8b4135 c94734b2-f2e1-11f0-a15d-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=38362 Onkološki inštitut Ljubljana 0 0 0