期刊
GENE THERAPY
卷 7, 期 7, 页码 568-574出版社
STOCKTON PRESS
DOI: 10.1038/sj.gt.3301138
关键词
in vivo; airway epithelium; gene transfer; lentiviral vectors; HIV vectors
类别
资金
- NHLBI NIH HHS [HL58342] Funding Source: Medline
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 (70%, n = 4) than when vector was delivered on the day after SO2 exposure (1.7%, n = 4).
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