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

• Published in: Gene therapy Vol. 7; no. 7; pp. 568 - 574
• Main Authors: JOHNSON, L. G, OLSEN, J. C, NALDINI, L, BOUCHER, R. C
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.04.2000
• Subjects: Analysis of Variance; Animals; Basal cells; beta-Galactosidase - genetics; Biological and medical sciences; Biotechnology; Cell differentiation; Cell surface; Cells, Cultured; Epithelial cells; Epithelium; Epithelium - metabolism; Evaluation Studies as Topic; Fundamental and applied biological sciences. Psychology; Gene therapy; Gene transfer; Genetic Vectors - administration & dosage; glycoprotein G; Health. Pharmaceutical industry; HIV; Human immunodeficiency virus; human lentivirus; Humans; Industrial applications and implications. Economical aspects; Lentivirus; Lentivirus - genetics; Mice; Rats; Respiratory System - metabolism; Respiratory tract; Stomatitis; Sulfur dioxide; Transfection - methods; Vesicular stomatitis virus; Animal model; Upper respiratory tract; Recombinant virus; Rodentia; Retroviridae; Epithelium; Gene expression; Lentivirus; Sulfur dioxide; Genetic transfer; Virus; Vertebrata; Mammalia; Reporter gene; Human immunodeficiency virus; Gene therapy; Vector
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3301138

We used a replication defective human lentiviral (HIV) vector encoding the lacZ cDNA and pseudotyped with the vesicular stomatitis virus (VSV) glycoprotein (G) to evaluate the utility of this vector system in airway epithelia. In initial studies, apical application of vector to polarized well differentiated human airway epithelial cell cultures produced minimal levels of transgene expression whereas basolateral application of vector enhanced levels of transduction approximately 30-fold. Direct in vivo delivery of HIV vectors to the nasal epithelium and tracheas of mice failed to mediate gene transfer, but injury with sulfur dioxide (SO2) before vector delivery enhanced 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 to basal cells and/or the basolateral membrane of airway surface epithelial cells. Quantification of gene transfer efficiency in murine tracheas demonstrated that transduction was more efficient when vector was delivered on the day of exposure (7.0%, n = 4) than when vector was delivered on the day after SO2 exposure (1.7%, n = 4).