Widespread airway distribution and short-term phenotypic correction of cystic fibrosis pigs following aerosol delivery of piggyBac/adenovirus

Nucleic Acids Research
Ashley L CooneyPatrick L Sinn

Abstract

Cystic fibrosis (CF) is a common genetic disease caused by mutations in the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR). Although CF affects multiple organ systems, chronic bacterial infections and inflammation in the lung are the leading causes of morbidity and mortality in people with CF. Complementation with a functional CFTR gene repairs this defect, regardless of the disease-causing mutation. In this study, we used a gene delivery system termed piggyBac/adenovirus (Ad), which combines the delivery efficiency of an adenoviral-based vector with the persistent expression of a DNA transposon-based vector. We aerosolized piggyBac/Ad to the airways of pigs and observed widespread pulmonary distribution of vector. We quantified the regional distribution in the airways and observed transduction of large and small airway epithelial cells of non-CF pigs, with ∼30-50% of surface epithelial cells positive for GFP. We transduced multiple cell types including ciliated, non-ciliated, basal, and submucosal gland cells. In addition, we phenotypically corrected CF pigs following delivery of piggyBac/Ad expressing CFTR as measured by anion channel activity, airway surface liquid pH, and bacterial killing abilit...Continue Reading

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Citations

Nov 9, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Leah R ReznikovKevin Vogt
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Aug 31, 2021·Molecular Therapy. Nucleic Acids·Ashley L CooneyPatrick L Sinn

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Methods Mentioned

BETA
electron microscopy
confocal microscopy
bronchoalveolar lavage
PCR
ELISAs

Software Mentioned

GraphPad
ImageJ
Graphpad Prism

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