20.500.12556/DiRROS-18738 Safety and efficacy of IL-12 plasmid DNA transfection into pig skin supportive data for human clinical trials on gene therapy and vaccination Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment of various types of tumors in human oncology and as an adjuvant in DNA vaccines. In recent years, we have developed a plasmid encoding human IL-12 (phIL12) that is currently in a phase I clinical study. The aim was to confirm the results of a non-clinical study in mice on pharmacokinetic characteristics and safety in a porcine model that better resembled human skin. The GET of phIL12 in the skin was performed on nine pigs using different concentrations of plasmid phIL12 and invasive (needle) or noninvasive (plate) types of electrodes. The results of our study demonstrate that the GET of phIL-12 with needle electrodes induced the highest expression of IL-12 at the protein level on day 7 after the procedure. The plasmid was distributed to all tested organs; however, its amount decreased over time and was at a minimum 28 days after GET. Based on plasmid copy number and expression results, together with blood analysis, we showed that IL-12 GET is safe in a porcine animal model. Furthermore, we demonstrated that pigs are a valuable model for human gene therapy safety studies. interleukin 12 gene electrotransfer immunotherapy interlevkin 12 elektroprenos genov imunoterapija true false true MDPI Basel, Switzerland Angleški jezik Slovenski jezik by Authors Neznano 2024-04-18 14:01:54 2024-04-18 14:01:54 2024-05-14 12:46:00 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 9. 4. 2024; str. 3151-1-3151-12 no. 6 Vol. 25 2024 0000-00-00 Zaloznikova Objavljeno apc 2023-11-27 2024-03-06 2024-03-09 602 1422-0067 10.3390/ijms25063151 191795459 https://www.mdpi.com/1422-0067/25/6/3151 1 b0b8e382-fd6a-11ee-ae20-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=25641 RAZ_Lampreht_Tratar_Ursa_2024.pdf RAZ_Lampreht_Tratar_Ursa_2024.pdf 1 F61407EF65A3DEE02520CB25A3B9E701 e71d8a686439bf30bd5bde347da9eaa6297e56e14fd91cbc2a412d4ddfb2a385 3a18a825-fd6d-11ee-ae20-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=25642 Onkološki inštitut Ljubljana 0 0 0