Safety and efficacy of IL-12 plasmid DNA transfection into pig skin : supportive data for human clinical trials on gene therapy and vaccination

Lampreht Tratar, Urša (avtor), Jesenko, Tanja (avtor), Omerzel, Maša (avtor), Seliškar, Alenka (avtor), Stupan, Urban (avtor), Djokić, Mihajlo (avtor), Sredenšek, Jerneja (avtor), Trotovšek, Blaž (avtor), Serša, Gregor (avtor), Čemažar, Maja (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: interleukin 12, gene electrotransfer, immunotherapy, porcine model, oncology
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: VF - Veterinarska fakulteta ; MF - Medicinska fakulteta ; FFA - Fakulteta za farmacijo ; ZF - Zdravstvena fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 12 str.
• Številčenje: Vol. 25, iss. 6, art. 3151
• PID: 20.500.12556/RUL-164966
• UDK: 602
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms25063151
• COBISS.SI-ID: 191795459
• Datum objave v RUL: 19.11.2024

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: interlevkin 12, elektroprenos genov, imunoterapija

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0003
• Naslov: Razvoj in ovrednotenje novih terapij za zdravljenje malignih tumorjev

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P4-0053
• Naslov: Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih