Low-cost, handheld, multi-pulse electroporators for simplified nucleic acid delivery in skin

Electroporation-mediated delivery offers a promising alternative to carrier-based nucleic acid delivery methods for vaccination and therapeutic applications. Carrier-based systems like lipid nanoparticles and viral vectors often suffer from poor in vivo stability, immunogenicity, toxicity, and off-target effects. To overcome the high cost, bulkiness, lack of portability, and painful administration of traditional electroporators, we developed the RotoPatch family of small, low-cost, hand-held piezoelectric electroporators that use microneedle electrodes for intradermal delivery of nucleic acids. Notably, these RotoPatch devices use a single rotary motion to administer multiple electroporation pulses through microneedle electrodes, that localize the electric field to the upper layers of the skin. In animals, RotoPatch facilitated greater intracellular uptake of firefly luciferase-encoded mRNA in mice and green fluorescent protein-encoded plasmid DNA in rats, as confirmed by bioluminescence and fluorescence imaging, respectively. RotoPatch produced similar in vivo expression as electroporation using a manually actuated, multi-pulse piezoelectric electroporator (ePatch) and a battery-powered, multi-pulse electroporator (eIgniter). These findings highlight the potential of multi-pulse piezoelectric microneedle electroporation for intradermal nucleic acid delivery as a platform for gene therapy and vaccination.