Adenoviral Gene Transfer Corrects the Ion Transport Defect in the Sinus Epithelia of a Porcine CF Model

Andrea E Potash; Tanner J Wallen; Philip H Karp; Sarah Ernst; Thomas O Moninger; Nicholas D Gansemer; David A Stoltz; Joseph Zabner; Eugene H Chang

doi:10.1038/mt.2013.49

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Adenoviral Gene Transfer Corrects the Ion Transport Defect in the Sinus Epithelia of a Porcine CF Model

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Adenoviral Gene Transfer Corrects the Ion Transport Defect in the Sinus Epithelia of a Porcine CF Model

Andrea E Potash, Tanner J Wallen, Philip H Karp, Sarah Ernst, Thomas O Moninger, Nicholas D Gansemer, David A Stoltz, Joseph Zabner and Eugene H Chang

Molecular therapy, Vol.21(5), pp.947-953

05/2013

DOI: 10.1038/mt.2013.49

PMCID: PMC3666638

PMID: 23511247

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Abstract

Cystic fibrosis (CF) pigs spontaneously develop sinus and lung disease resembling human CF. The CF pig presents a unique opportunity to use gene transfer to test hypotheses to further understand the pathogenesis of CF sinus disease. In this study, we investigated the ion transport defect in the CF sinus and found that CF porcine sinus epithelia lack cyclic AMP (cAMP)-stimulated anion transport. We asked whether we could restore CF transmembrane conductance regulator gene ( CFTR ) current in the porcine CF sinus epithelia by gene transfer. We quantified CFTR transduction using an adenovirus expressing CFTR and green fluorescent protein (GFP). We found that as little as 7% of transduced cells restored 6% of CFTR current with 17–28% of transduced cells increasing CFTR current to 50% of non-CF levels. We also found that we could overcorrect cAMP-mediated current in non-CF epithelia. Our findings indicate that CF porcine sinus epithelia lack anion transport, and a relatively small number of cells expressing CFTR are required to rescue the ion transport phenotype. These studies support the use of the CF pig as a preclinical model for future gene therapy trials in CF sinusitis.

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Title: Subtitle: Adenoviral Gene Transfer Corrects the Ion Transport Defect in the Sinus Epithelia of a Porcine CF Model
Creators: Andrea E Potash - , Iowa City, Iowa
Tanner J Wallen - , Iowa City, Iowa
Philip H Karp - , Iowa City, Iowa
Sarah Ernst - , Iowa City, Iowa
Thomas O Moninger - , Iowa City, Iowa
Nicholas D Gansemer - , Iowa City, Iowa
David A Stoltz - , Iowa City, Iowa
Joseph Zabner - , Iowa City, Iowa
Eugene H Chang - , Iowa City, Iowa
Resource Type: Journal article
Publication Details: Molecular therapy, Vol.21(5), pp.947-953
DOI: 10.1038/mt.2013.49
PMID: 23511247
PMCID: PMC3666638
NLM abbreviation: Mol Ther
ISSN: 1525-0016
eISSN: 1525-0024
Publisher: Nature Publishing Group
Language: English
Date published: 05/2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984025413402771

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