Document Detail


High efficiency gene transfer to airways of mice using influenza hemagglutinin pseudotyped lentiviral vectors.
MedLine Citation:
PMID:  23319179     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: A limitation to efficient lentivirus-mediated airway gene transfer is the lack of receptors to commonly used viral envelopes on the luminal surface of airway epithelia. The use of viral envelopes with natural tropism to the airway could be useful for overcoming this limitation. METHODS: We investigated influenza hemagglutinin (HA) pseudotyped EIAV-derived lentiviral vector-mediated gene transfer to the airway epithelium of adult and newborn mice. For these studies high-titer vectors were delivered by intranasal administration. In addition, we tested the feasibility of vector re-dosing to the nasal airway. RESULTS: Delivery of high-titer HA pseudotyped lentiviral vectors by nasal administration to newborn mouse pups or adult mice results in efficient transduction of airway epithelial cells in the nose, trachea, and lungs. In the nose vector expression was predominant in the respiratory epithelium and was not observed in the olfactory epithelium. In the trachea and large airways of the lung approximately 46% and 40%, respectively, of surface epithelial cells could be transduced. The efficiency of re-dosing to the nasal airway of mice was found to be dependent upon the age of the animal when the first dose is administered and the length of time between doses. CONCLUSIONS: A single intranasal dose of concentrated influenza HA-pseudotyped lentiviral vector is sufficient for efficient gene transfer to the airways of mice. This is a promising result that could lead to the development of effective gene transfer reagents for the treatment of cystic fibrosis and other human lung diseases. Copyright © 2013 John Wiley & Sons, Ltd.
Authors:
Manij Patel; Angela M Giddings; John Sechelski; John C Olsen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-14
Journal Detail:
Title:  The journal of gene medicine     Volume:  -     ISSN:  1521-2254     ISO Abbreviation:  J Gene Med     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 John Wiley & Sons, Ltd.
Affiliation:
Cystic Fibrosis/Pulmonary Research and Treatment Center, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
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