CENTRO DE SIMULACION COMPUTACIONAL PARA APLICACIONES TECNOLOGICAS
Unidad Ejecutora - UE
Tissue damage modeling in gene electrotransfer: The role of pH
OLAIZ, N.; SIGNORI, E.; MAGLIETTI, F.; SOBA, A.; SUAREZ, C.; TURJANSKI, P.; MICHINSKI, S.; MARSHALL, G.
ELSEVIER SCIENCE SA
Lugar: Amsterdam; Año: 2014 vol. 100 p. 105 - 105
Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efﬁciency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson?Nernst?Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes andthat these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling conﬁrms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efﬁciency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric ﬁeld applied is near 183 V/cm in a GET protocol and 158 V/cm in a hyaluronidase + GET protocol.