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Developement of a realistic mathematical model for prediction of efficient and safe clinical gene electrotransfer

STSM by Selma Čorović, Early-Stage Researcher

Period of mission: from 19/01/2014 to 30/01/2014

Home institution: Laboratory of Biocybernetics, University of Ljubjana, Faculty of Electrical Engineering, Ljubljana, Slovenia

Host institution: Department of Oncology, Center for Experimental Drug and Gene Electrotransfer, Copenhagen University Hospital Herlev, Herlev, Denmark

During the STSM at the Copenhagen University Hospital Herlev in Denmark we developed a realistic mathematical model that would help in prediction of efficient and safe clinical gene electrotransfer to muscle tissue. The primary objective of the work was to validate the model with clinical data obtained during the phase I clinical study of gene therapy for patients with advanced solid tumors. In addition, we validated the calculated electric field distribution with the spatial distribution of transgenic protein expressed in porcine muscle. We found the perpendicular orientation of electric field with respect to the muscle fibers to be optimal for efficient and safe gene electrotransfer. Due to the anisotropy of muscle tissue other orientations of electric field with respect to the muscle fibers resulted in a higher electric current, larger volume of irreversibly electroporated muscle and lower volume of reversibly electroporatad muscle. These results provide a clearer understanding of the influence of muscle anisotropy on delineation of successfully electroporated muscle area, and subsequently on the efficacy of gene electrotransfer. The precise location of the transfected muscle area is also important for the post-transfection interventions in case of adverse events when the gene expression in the located area needs to be terminated. In addition to gene therapy performed by gene electrotransfer to muscle tissue, our results can be important also in DNA vaccination and local intramuscular gene transfection.


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