The use of silencing RNA (siRNA) represents not only a potentially powerful experimental approach to allow us to better understand the evolving pathology of ALI, but may possibly represent a novel therapeutic approach to the treatment of this condition. The history of siRNA, its discovery, development, the mechanisms involved, as well as its successful initial uses in mammals in vivo are described elsewhere (153) (154) (155) (156) . With respect to its application in vivo, the lung appears to be a good candidate, as it can be accessed straightforwardly intranasally (i.n.) or intratracheally (i.t.). Nevertheless, nucleic acid transfer efficiency can be diminished substantially by phospholipids and proteins, which are major components of the airway surface liquid (157) . Interestingly, unlike systemically, delivery of naked siRNA into the lungs has proven very efficient (152, 158, 159) , thus potentially complex and costly approaches using vector systems or chemical siRNA modifications may not be necessary. In this regard, the delivery of siRNA inhibitors of SARS coronavirus in 5% glucose was superior, even in reducing the severity of the disease, than when given in modified calf pulmonary surface active material (160) . As early as 2004, the feasibility of a surfactantbased or naked siRNA approach in the mouse lung targeting glyceraldehyde-3phosphate dehydrogenase (GAPDH) or heme oxygenase-1 during ischemiareperfusion, respectively, has been demonstrated (161, 162) . Phase I/II trials for Respiratory Syncytial Virus have been conducted and are now on their way to evaluate the safety, tolerability, and antiviral activity of siRNA treatment in human lungs (155, 158, 163) .