J-FD was an investigator in the PROWESS study and is a consultant for Eli Lilly and Company. Y-EC declares that he has no competing interests.  Simian virus 40 vectors for pulmonary gene therapy BACKGROUND: Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy. METHODS: Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/luc) were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector. RESULTS: Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response. CONCLUSION: In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool. Sepsis is the leading cause of death in critically ill patients [1] . Despite advances in treating the sepsis syndrome, the incidence and mortality of sepsis remains high (35-45%) [2] . Lung is the organ most often involved, with lung injury taking the form of Acute Respiratory Distress Syndrome (ARDS) [3] [4] [5] , carrying 40% mortality [6] . The pathological hallmark of ARDS is airspace flooding with proteinaceous fluid, basement membrane disruption, hyaline membrane deposition, surfactant depletion, interstitial swelling, and interstitial neutrophilic infiltration [7] . Histological sections of the lungs from patients dying of ARDS and from animal models of the disease reveal: interstitial edema, followed by extensive necrosis of alveolar epithelial cells [8] .