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|Title:||Single-dose lentiviral gene transfer for lifetime airway gene expression|
|Citation:||Journal of Gene Medicine, 2009; 11(10):861-867|
|Publisher:||John Wiley & Sons Ltd|
|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.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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