The lung endothelium has been studied as one of the most important sites for systemic DNA delivery using nonviral vectors. This is because not only does the lung play a critical role in maintaining the O2 /CO2 concentration in blood, but it also has the largest capillary bed and an extensive cell surface area to allow DNA to bind to and enter the endothelial cells. An additional advantage of the lung endothelium for DNA delivery is that the entire blood volume circulates through the lung and thus, the intravenously injected DNA molecules have full excess to the lung endothelium. Furthermore, blood flow through the pulmonary capillaries is slow and discontinuous. On inspiration, as the alveoli fill with air, blood flow slows and stops. On expiration, blood flow resumes. Slower blood flow in the lung favors DNA binding to the endothelial cells.