Noninvasive gene delivery to the liver by mechanical massage

With the recent completion of the human genome project and the tremendous growth of biotechnology, the desire to extract information concerning gene expression, protein level, subcellular localization, and functionality in the liver will demand the development of efficient gene transfer to this organ with minimal toxicity. In this report, we show that significant gene expression in the liver could be achieved by simple mechanical massage after intravenous injection of naked plasmid DNA into mice. This method is simple, highly reproducible, repeatable, and, more importantly, free of toxicity. Hepatic gene transfer with hepatocyte growth factor (HGF) plasmid DNA prevented endotoxin-induced lethal fulminant hepatic failure, leading to dramatically enhanced survival in mice.