Cyclin B1 knockdown mediated by clinically approved pulsed electric fields siRNA delivery induces tumor regression in...

RNA interference (RNAi) represents a promising therapy for the specific inhibition of gene expression in targeted tissues including tumors. To realize the therapeutic potential of RNAi drugs, non-immunogenic, efficient, and tissue-specific delivery technologies must be developed. We have previously shown that pulsed electric field (PEF) can deliver siRNAs into tumor cells thanks to long electrophoretic drift occurring during the use of millisecond duration pulses. Here, optical fluorescence imaging is used at first to evaluate the efficiency of microsecond-duration pulses for siRNA delivery. These pulsed electric fields (PEF) parameters, which are already used in clinics for electrochemotherapy (ECT) were compared to previous parameters optimized for electrogenotherapy (EGT) that use microsecond-duration pulses. Secondly, these PEF protocols were evaluated for the delivery of specific siRNAs targeting the cyclin B1 in subcutaneous tumors in mice. When a single treatment was performed, millisecond duration pulses led to a better efficiency. However, when multiple treatments were performed, both protocols were equally efficient and potentially silenced cyclin B1 endogenous gene, leading to a tumor growth reduction. Our findings provide insights into pulsed electric field-siRNA delivery that could benefit from existing clinical protocols for siRNA delivery to tumors.