1. ¹Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, 98105, USA
2. ²Evanston Northwestern Healthcare, Evanston, Illinois, 60201, USA
3. ³Northwestern University Medical School, Chicago, Illinois, 60611, USA

Correspondence: Daniel J. Weiss, Fax: (802) 656-8926. E-mail: daniel.weiss@vtmednet.org

Received 21 July 2001; Accepted 7 May 2002.

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 410⁹ 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-l aliquots of virus suspended in a 50% surfactant (Survanta) vehicle over a 15-minute period. PFC rats received virus in 100 l 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 -galactosidase (-gal) expression and indices of inflammation. Both PFC liquid and surfactant-based vehicles produced widespread -gal expression and increased total -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. FC-75 was also associated with increased BALF IL1. In conclusion, surfactant and FC-75 are similarly effective vehicles for adenovirus-mediated gene transfer to the lung.