Opening the Floodgates: Clinically Applicable Hydrodynamic Delivery of Plasmid DNA to Skeletal Muscle

Abstract

viruses compared to other tissues such as liver. However, the efficiency of naked plasmid gene transfer is very low following simple intramuscular injection. Fortunately, developments over the last several years have dramatically improved the efficiency of plasmid-based gene delivery. These developments are all physical, providing a motive force to drive the plasmid into close association with the muscle fiber membrane and/or transiently increasing membrane permeability. These methods include in vivo electroporation and hydrodynamic (pressure-mediated) vascular delivery. Electroporation dramatically increases the efficiency of plasmid gene transfer by several orders of magnitude, but the effect is limited to the region between the electrodes and thus multiple injections would still be required for each muscle. In contrast, using a combination of large volumes and rapid injection into the iliac artery, Jon Wolff’s group demonstrated delivery to multiple muscles of