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

L. G. Johnson, J. C. Olsen, L. Naldini, R. C. Boucher

Research output: Contribution to journalArticle

Abstract

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).

Original languageEnglish
Pages (from-to)568-574
Number of pages7
JournalGene Therapy
Volume7
Issue number7
Publication statusPublished - Apr 2000

Keywords

  • Airway epithelium
  • Gene transfer
  • HIV vectors
  • In vivo
  • Lentiviral vectors

ASJC Scopus subject areas

  • Genetics

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    Johnson, L. G., Olsen, J. C., Naldini, L., & Boucher, R. C. (2000). Pseudotyped human lentiviral vector-mediated gene transfer to airway epithelia in vivo. Gene Therapy, 7(7), 568-574.