Transducing the acutely injured lung may be diffi cult, due to the presence of pulmonary edema, consolidated or collapsed alveoli, and additional extracellular barriers such as mucus. Gene-based therapies targeted at the pulmonary epithelium may be less eff ective where there is extensive denudation of the pulmonary epithelium, as may occur in primary ARDS. Encouragingly, there is some evidence to suggest that ALI may not substantially impair viral gene transfer to the alveolar epithelium [47] .