Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/112933
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Role of basal cells in producing persistent lentivirus-mediated airway gene expression
Author: Farrow, N.
Donnelley, M.
Cmielewski, P.
Roscioli, E.
Rout-Pitt, N.
McIntyre, C.
Bertoncello, I.
Parsons, D.
Citation: Human Gene Therapy, 2018; 29(6):653-662
Publisher: Mary Ann Liebert
Issue Date: 2018
ISSN: 1043-0342
1557-7422
Statement of
Responsibility: 
Nigel Farrow, Martin Donnelley, Patricia Cmielewski, Eugene Roscioli, Nathan Rout-Pitt, Chantelle McIntyre, Ivan Bertoncello, and David W. Parsons
Abstract: Cystic fibrosis (CF) lung disease is an ideal candidate for a genetic therapy. It has been shown previously that preconditioning with lysophosphatidylcholine (LPC) prior to lentiviral (LV) vector delivery results in long-term in vivo gene expression in the airway epithelium of CF mice. It was hypothesized that this outcome is largely due to transduction of airway basal cells that in turn pass the transgene onto their progeny. The aim of these studies was to confirm if the in vivo delivery of a human immunodeficiency virus type 1 (HIV-1) vesicular stomatitis virus envelope glycoprotein (VSV-G) pseudotyped LV vector following LPC airway conditioning results in transduction of mouse airway basal cells in situ and if the transgene is passed onto their progeny. Additionally, the study sought to determine the efficiency of in vitro transduction of human airway basal cells. First, normal mouse nasal airways were pretreated with LPC prior to delivery of a HIV-1 VSV-G pseudotyped LV vector carrying a LacZ marker gene (LV-LacZ). An epithelial ablation model utilizing polidocanol was then used to demonstrate that clonal outgrowth of linear and spotted clusters of transgene expressing ciliated, basal, and goblet cells occurs following transduction of basal cells. Second, human basal cells were cultured from primary bronchial epithelial cells, with identity confirmed by keratin 5 staining. High levels of transgene expression were found following LV-LacZ transduction. This study demonstrates the ability of the vector delivery protocol to transduce mouse airway basal cells, the LV vector to transduce human basal cells, and the likely role of these cells in maintaining long-term gene expression. These findings support and further develop the potential of LV gene transfer for persistent correction of CF airway disease.
Keywords: cystic fibrosis; lentivirus; airway basal progenitor cell
Rights: © 2018 by Mary Ann Liebert, Inc.
RMID: 0030078555
DOI: 10.1089/hum.2017.059
Grant ID: http://purl.org/au-research/grants/nhmrc/1098127
Appears in Collections:Paediatrics publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.