Fig. 1.

TNT can be used to deliver nucleic acids to genes in a safe and efficient manner. (a) Schematic diagram of the experimental procedure. The sciatic nerve is first surgically exposed, and the nanochanneled surface of the TNT platform is put in direct contact with the nerve. A negative electrode is immersed into the plasmid reservoir and a positive electrode is inserted into the muscle adjacent to the nerve. A pulsed electric field is then applied across electrodes to nanoporate the tissue surface and electrophoretically drive nucleic acids into the nerve. (b, c) Finite element modeling simulations of the electric field distribution when the poration is mediated by nanochannels. Dashed red line shows the voltage distribution for bulk electroporation. Nanochannel-mediated poration enables focused implementation of the electric field (solid blue line). (d) Fluorescence micrograph of the nerve cross-section following TNT with labeled plasmid DNA (green) at 0 vs. 200 volts. The plasmid DNA accumulates preferentially within the epineurium of the TNT-treated nerve surface. Inset to the right shows higher magnification image of the labeled plasmid within the epineurium. (e) Neuromuscular activity was evaluated via compound muscle action potential (CMAP) measurements in mice that underwent surgery to expose the sciatic nerve (control) vs. mice that underwent the surgery in addition to TNT- or BEP-based poration of the nerve (n = 3). While BEP led to a significant decrease in CMAP amplitude, TNT did not cause any significant changes. Mean ± sem, *p<0.001 vs. control (One Way Anova).