Comparison of surfactant and perfluorochemical liquid enhanced adenovirus-mediated gene transfer in normal rat lung

Both surfactant- and perfluorochemical (PFC)-based vehicles enhance adenovirus-mediated gene transfer in the lung. To compare the relative effects of surfactant and PFC liquid, we infected orotracheally intubated Sprague-Dawley rats with 4 × 10⁹ pfu of an E1a^-/E3^- adenovirus expressing either an Escherichia coli lacZ (AdlacZ) mini-gene or no cDNA Adnull). Surfactant-mediated delivery was achieved via instillation of four, 200-μl aliquots of virus suspended in a 50% surfactant (Survanta) vehicle over a 15-minute period. PFC rats received virus in 100 μl of saline followed by instillation of the PFC liquid FC-75 (10 cc/kg body weight) over a 2- to 3- minute period. Lungs were collected 3 days later for measurement of β-galactosidase (β-gal) expression and indices of inflammation. Both PFC liquid and surfactant-based vehicles produced widespread β-gal expression and increased total β-gal activity over that observed with instillation of vector alone. Both vehicles comparably increased bronchoalveolar lavage fluid (BALF), total cell counts, neutrophils, total protein, and IFNγ. FC-75 was also associated with increased BALF IL1β. In conclusion, surfactant and FC-75 are similarly effective vehicles for adenovirus-mediated gene transfer to the lung.