ABSTRACT: 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 x 10(9) 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-microl aliquots of virus suspended in a 50% surfactant (Survanta) vehicle over a 15-minute period. PFC rats received virus in 100 microl 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 beta-galactosidase (beta-gal) expression and indices of inflammation. Both PFC liquid and surfactant-based vehicles produced widespread beta-gal expression and increased total beta-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 IFN(gamma). FC-75 was also associated with increased BALF IL1beta. In conclusion, surfactant and FC-75 are similarly effective vehicles for adenovirus-mediated gene transfer to the lung.
Molecular Therapy 08/2002; 6(1):43-9. · 6.87 Impact Factor