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Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV)-mediated gene transfer was more efficient in the nasal airways...

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Autores principales: Oakland, Mayumi, Maury, Wendy, McCray, Paul B, Sinn, Patrick L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564419/
https://www.ncbi.nlm.nih.gov/pubmed/23360952
http://dx.doi.org/10.1038/mtna.2012.60
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author Oakland, Mayumi
Maury, Wendy
McCray, Paul B
Sinn, Patrick L
author_facet Oakland, Mayumi
Maury, Wendy
McCray, Paul B
Sinn, Patrick L
author_sort Oakland, Mayumi
collection PubMed
description Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV)-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN) responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV) in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.
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spelling pubmed-35644192013-02-05 Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors Oakland, Mayumi Maury, Wendy McCray, Paul B Sinn, Patrick L Mol Ther Nucleic Acids Methods - Original Article Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV)-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN) responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV) in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction. Nature Publishing Group 2013-01 2013-01-29 /pmc/articles/PMC3564419/ /pubmed/23360952 http://dx.doi.org/10.1038/mtna.2012.60 Text en Copyright © 2013 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/3.0/ Molecular Therapy-Nucleic Acids is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Methods - Original Article
Oakland, Mayumi
Maury, Wendy
McCray, Paul B
Sinn, Patrick L
Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors
title Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors
title_full Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors
title_fullStr Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors
title_full_unstemmed Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors
title_short Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors
title_sort intrapulmonary versus nasal transduction of murine airways with gp64-pseudotyped viral vectors
topic Methods - Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564419/
https://www.ncbi.nlm.nih.gov/pubmed/23360952
http://dx.doi.org/10.1038/mtna.2012.60
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