Pseudotyped human lentiviral vector-mediated gene transfer to airway epithelia in vivo

We used a replication defective human lentiviral (HIV) vector encoding the lacZ cDNA and pseudotyped with the vesicular stomatitis virus (VSV) glycopr otein (G) to evaluate the utility of this vector system in airway epithelia . In initial studies, apical application of vector to polarized well differ entiated human airway epithelial cell cultures produced minimal levels of t ransgene expression whereas basolateral application of vector enhanced leve ls of transduction approximately 30-fold. Direct in vivo delivery of HIV ve ctors to the nasal epithelium and tracheas of mice failed to mediate gene t ransfer, but injury with sulfur dioxide (SO2) before vector delivery enhanc ed gene transfer efficiency to the nasal epithelium of both mice and rats. SO2 injury also enhanced HIV vector-mediated gene transfer to the tracheas of rodents. These data suggest that SO2 injury increases access of vector t o basal cells and/or the basolateral membrane of airway surface epithelial cells. Quantification of gene transfer efficiency in murine tracheas demons trated that transduction was more efficient when vector was delivered on th e day of exposure (70%, n = 4) than when vector was delivered on the day af ter SO2 exposure (1.7%, n = 4).