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Gene delivery to airway epithetiat cells in vivo: a direct comparison of apicat and basotateral transduction strategies using pseudotyped, lentivirus vectors

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dc.contributor.authorKremer, K.
dc.contributor.authorDunning, K.
dc.contributor.authorParsons, D.
dc.contributor.authorAnson, D.
dc.date.issued2007
dc.descriptionPublished in Journal of Gene Medicine, 2007; 9 (5):362-368 at www.interscience.wiley.com
dc.description.abstractLentivirus vectors are being investigated as gene delivery vehicles for cystic fibrosis airway gene therapy. Vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped vectors transduce airway epithelia via receptors that are located predominantly on the basolateral surface of the airway epithelium. Effective transduction with VSV-G-pseudotyped vectors requires the use of a pre-treatment that disrupts epithelial tight junctions, allowing access to these basolateral receptors. In contrast, it has been reported that apically targeted lentiviral vectors allow efficient gene transfer in the absence of any pre-treatment. In a direct comparison of transduction by a VSV-G-pseudotyped vector, in combination with a pre-treatment with lysophosphatidylcholine (LPC), and the same vector pseudotyped with the apically targeted baculovirus GP64 envelope (without any pre-treatment), the GP64 vector was found to be significantly less efficient. However, when a pre-treatment with LPC was used the level of transduction with the GP64-pseudotyped lentiviral vector was not significantly different to that resulting from the VSV-G-pseudotyped vector. The cell types transduced with each vector were essentially the same, with the majority of cells transduced being respiratory (ciliated cells). However, unlike the VSV-G-pseudotyped vector, which results in persisting gene expression, transduction with the GP64-pseudotyped vector resulted in gene expression that declined to undetectable levels over six months, whether or not an LPC pre-treatment was used.
dc.description.statementofresponsibilityKarlea L. Kremer, Kylie R. Dunning, David W. Parsons, Donald S. Anson
dc.identifier.citationJournal of Gene Medicine, 2007; 9(5):362-368
dc.identifier.doi10.1002/jgm.1025
dc.identifier.issn1099-498X
dc.identifier.issn1521-2254
dc.identifier.orcidDunning, K. [0000-0002-0462-6479]
dc.identifier.orcidParsons, D. [0000-0002-8775-3501] [0000-0003-1746-3290]
dc.identifier.urihttp://hdl.handle.net/2440/44027
dc.language.isoen
dc.publisherJohn Wiley & Sons Ltd
dc.rightsCopyright status unknown
dc.source.urihttp://www3.interscience.wiley.com/journal/114191590/abstract
dc.subjectlentiviral vector
dc.subjectpseudotype
dc.subjectairway
dc.subjecttransduction
dc.subjectapical
dc.subjectbasolateral
dc.titleGene delivery to airway epithetiat cells in vivo: a direct comparison of apicat and basotateral transduction strategies using pseudotyped, lentivirus vectors
dc.typeJournal article
pubs.publication-statusPublished

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