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https://hdl.handle.net/2440/56892
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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 1521-2254 |
Statement of Responsibility: | 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. |
DOI: | 10.1002/jgm.1368 |
Grant ID: | NHMRC |
Published version: | http://dx.doi.org/10.1002/jgm.1368 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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