Use of Electroporation for Efficacious Gene Delivery to the Lungs

Abstract

We are interested in developing gene therapy treatments for pulmonary diseases, including acute lung injury. Recent research from our laboratory and others has demonstrated that electroporation can be used to efficiently deliver 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 either side of the chest are used to deliver the field. In studies in mice and rats, 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, but more importantly, we have also shown that this approach can be used in lungs with established lung injury and pulmonary edema to treat the disease and lessen the severity of the injury. To move this toward clinical use, we have evaluated these techniques in a large animal pig model that closely resembles the human situation. The approach is safe and effective, paving the way to clinical use.