Use of Electroporation for Efficacious Gene Delivery to the Lungs

We are interested in developing gene therapy treatments for pulmonary diseases, including acute lung injury. We have demonstrated that electroporation efficiently delivers genes to the lung in vivo with no apparent damage and yields high level gene expression. The method is simple, fast, and safe: DNA is delivered to the airways and electrodes placed externally on the chest are used to deliver the field. In mouse and rat studies we have demonstrated that transfer of genes for the Na+,K+-ATPase and/or the Epithelial Sodium Channel protects from subsequent endotoxin-induced lung injury. We have also shown that this approach can be used in lungs with established lung injury to treat the disease and lessen the severity of the injury. To move this toward clinical use, we have evaluated these techniques in a pig model that closely resembles the human situation. The approach is safe and effective, paving the way to clinical use.