title: Changing electrode orientation, but not pulse polarity, increases the efficacy of gene electrotransfer to tumors in vivo.
abstract: Gene electrotransfer is an established method for plasmid delivery into different tissues. Contrary to extensive in vitro studies demonstrating increased gene electrotransfer by changing the electric field direction during the pulse delivery, little is known about the efficiency of both polarities pulses in vivo. Therefore the aim of our study was to evaluate the effect of pulse polarity and orientation on the efficacy of gene electrotransfer in the murine fibrosarcoma tumor model by using the luciferase and GFP reporter gene expression plasmids. Our results demonstrated no significant difference in luciferase activity, GFP transfected area or fluorescence intensity between different sets of electric pulses. Inversion of the pulse polarity did not result in the increase of gene transfer, but non-significant enhancement up to 7-fold was detected by changing the electric field orientation in perpendicular direction. Also, transfection of surrounding skin tissue was observed, meaning that intratumoral gene electrotransfer could also result in a systemic effect. Our data indicate that tested modifications of electric pulses are not significantly affecting the efficiency of gene electrotransfer to LPB tumors. Biological factors, like tissue composition, might be of greater importance and should therefore also be taken into account when selecting the electric pulse parameters for specific tissues.
authors.affiliation: Institute of Oncology Ljubljana, Zaloska cesta 2, 1000 Ljubljana, Slovenia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Todorovic
authors.affiliation: Institute of Oncology Ljubljana, Zaloska cesta 2, 1000 Ljubljana, Slovenia.
authors.forename: Urska
authors.initials: U
authors.lastname: Kamensek
authors.affiliation: Institute of Oncology Ljubljana, Zaloska cesta 2, 1000 Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
authors.affiliation: Institute of Oncology Ljubljana, Zaloska cesta 2, 1000 Ljubljana, Slovenia; University of Primorska, Faculty of Health Sciences, Polje 42, 6310 Izola, Slovenia. Electronic address: mcemazar@onko-i.si.
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004566:Electrodes; D018274:Electroporation / Q000295:instrumentation / Q000379:methods*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D014162:Transfection / Q000295:instrumentation / Q000379:methods*
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008156:Luciferases
keywords: Electroporation; Gene electrotransfer; Murine fibrosarcoma; Pulse polarity; Skin