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Type: Journal article
Title: Single-dose lentiviral gene transfer for lifetime airway gene expression
Author: Stocker, A.
Kremer, K.
Koldej, R.
Miller, D.
Anson, D.
Parsons, D.
Citation: Journal of Gene Medicine, 2009; 11(10):861-867
Publisher: John Wiley & Sons Ltd
Issue Date: 2009
ISSN: 1099-498X
Statement of
Alice G. Stocker, Karlea L. Kremer, Rachel Koldej, Darren S. Miller, Donald S. Anson and David W. Parsons
Abstract: <h4>Background</h4>Cystic fibrosis (CF) is caused by a defect in cystic fibrosis transmembrane conductance regulator (CFTR) activity, often resulting in an incurable airway disease. Gene therapy into the conducting airway epithelium is a potential cure for CF; however, most gene vectors do not result in long-lived expression, and require re-dosing. Perversely, intrinsic host immune responses can then block renewed gene transfer.<h4>Methods</h4>To investigate whether persistent gene expression could be achieved after a single dosing event, thus avoiding the issue of blocking host responses, we used a gene transfer protocol that combined an airway pretreatment using lysophosphatidylcholine with a human immunodeficiency virus type-1 (vesicular stomatitis virus G pseudotype) derived lentiviral vector to test whether an integrating vector could produce gene expression able to last for a substantial part of the lifetime of the laboratory mouse.<h4>Results</h4>We found that a single dose of LV-LacZ produced immediate as well as lifetime mouse airway expression, confirming our hypothesis that use of an integrating vector extends transgene expression. Importantly, LV-CFTR dosing achieved at least 12 months of CFTR expression, representing partial functional correction of the CFTR defect in CF-null mice.<h4>Conclusions</h4>These findings validate the potential of this methodology for developing a gene transfer treatment for CF airway disease.
Keywords: cystic fibrosis; gene therapy; lentivirus; persistence; potential difference; reporter gene
Description: Copyright © 2010 John Wiley & Sons, Ltd.
RMID: 0020093077
DOI: 10.1002/jgm.1368
Appears in Collections:Molecular and Biomedical Science publications

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