Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung

We compared lung delivery methods of recombinant adenovirus (rAd): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined us...

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Main Authors: Jeffrey A. Kazzaz, Marlene S. Strayer, Jichuan Wu, Daniel J. Malone, Hshi-chi Koo, Thomas H. Shaffer, Jonathan M. Davis, David S. Strayer, Marla R. Wolfson
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Pulmonary Medicine
Online Access:http://dx.doi.org/10.1155/2011/918036
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author Jeffrey A. Kazzaz
Marlene S. Strayer
Jichuan Wu
Daniel J. Malone
Hshi-chi Koo
Thomas H. Shaffer
Jonathan M. Davis
David S. Strayer
Marla R. Wolfson
author_facet Jeffrey A. Kazzaz
Marlene S. Strayer
Jichuan Wu
Daniel J. Malone
Hshi-chi Koo
Thomas H. Shaffer
Jonathan M. Davis
David S. Strayer
Marla R. Wolfson
author_sort Jeffrey A. Kazzaz
collection DOAJ
description We compared lung delivery methods of recombinant adenovirus (rAd): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2–4 h. rAd transgene expression was improved in alveolar epithelial cells, and the level and distribution of luciferase expression when delivered in PFC-rAd suspensions consistently peaked at 24 h. These results demonstrate that PFC-rAd suspensions improve distribution and enhance rAd-mediated gene expression which has important implications in improving lung function by gene therapy.
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language English
publishDate 2011-01-01
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series Pulmonary Medicine
spelling doaj-art-4f3fc23b5ca449889e77e4a27e8126e12025-08-20T03:20:17ZengWileyPulmonary Medicine2090-18362090-18442011-01-01201110.1155/2011/918036918036Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal LungJeffrey A. Kazzaz0Marlene S. Strayer1Jichuan Wu2Daniel J. Malone3Hshi-chi Koo4Thomas H. Shaffer5Jonathan M. Davis6David S. Strayer7Marla R. Wolfson8The Cardiopulmonary Research Institute and Departments of Medicine and Pediatrics, SUNY Stony Brook School of Medicine, Winthrop University Hospital, Mineola, NY 11507, USADepartment of Pathology, Thomas Jefferson University Medical Center, Philadelphia, PA 19107, USADepartments of Physiology and Pediatrics, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USADepartments of Physiology and Pediatrics, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USAThe Cardiopulmonary Research Institute and Departments of Medicine and Pediatrics, SUNY Stony Brook School of Medicine, Winthrop University Hospital, Mineola, NY 11507, USADepartments of Physiology and Pediatrics, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USAThe Cardiopulmonary Research Institute and Departments of Medicine and Pediatrics, SUNY Stony Brook School of Medicine, Winthrop University Hospital, Mineola, NY 11507, USADepartment of Pathology, Thomas Jefferson University Medical Center, Philadelphia, PA 19107, USADepartments of Physiology and Pediatrics, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USAWe compared lung delivery methods of recombinant adenovirus (rAd): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2–4 h. rAd transgene expression was improved in alveolar epithelial cells, and the level and distribution of luciferase expression when delivered in PFC-rAd suspensions consistently peaked at 24 h. These results demonstrate that PFC-rAd suspensions improve distribution and enhance rAd-mediated gene expression which has important implications in improving lung function by gene therapy.http://dx.doi.org/10.1155/2011/918036
spellingShingle Jeffrey A. Kazzaz
Marlene S. Strayer
Jichuan Wu
Daniel J. Malone
Hshi-chi Koo
Thomas H. Shaffer
Jonathan M. Davis
David S. Strayer
Marla R. Wolfson
Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
Pulmonary Medicine
title Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
title_full Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
title_fullStr Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
title_full_unstemmed Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
title_short Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
title_sort perfluorochemical liquid adenovirus suspensions enhance gene delivery to the distal lung
url http://dx.doi.org/10.1155/2011/918036
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