Journal article
Lentiviral-mediated phenotypic correction of cystic fibrosis pigs
JCI insight, Vol.1(14), e88730
09/08/2016
DOI: 10.1172/jci.insight.88730
PMCID: PMC5027966
PMID: 27656681
Abstract
Cystic Fibrosis (CF) is an autosomal recessive disease caused by mutations in CF transmembrane conductance regulator (CFTR), resulting in defective anion transport. Regardless of the disease-causing mutation, gene therapy is a strategy to restore anion transport to airway epithelia. Indeed, viral vector–delivered CFTR can complement the anion channel defect. In this proof-of-principle study, functional in vivo CFTR channel activity was restored in the airways of CF pigs using a feline immunodeficiency virus–based (FIV-based) lentiviral vector pseudotyped with the GP64 envelope. Three newborn CF pigs received aerosolized FIV-CFTR to the nose and lung. Two weeks after viral vector delivery, epithelial tissues were analyzed for functional correction. In freshly excised tracheal and bronchus tissues and cultured ethmoid sinus cells, we observed a significant increase in transepithelial cAMP-stimulated current, evidence of functional CFTR. In addition, we observed increases in tracheal airway surface liquid pH and bacterial killing in CFTR vector–treated animals. Together, these data provide the first evidence to our knowledge that lentiviral delivery of CFTR can partially correct the anion channel defect in a large-animal CF model and validate a translational strategy to treat or prevent CF lung disease.
Details
- Title: Subtitle
- Lentiviral-mediated phenotypic correction of cystic fibrosis pigs
- Creators
- Ashley L Cooney - Departments of MicrobiologyMahmoud H Abou Alaiwa - Internal MedicineViral S Shah - Molecular Physiology and BiophysicsDrake C Bouzek - Internal MedicineMallory R Stroik - Internal MedicineLinda S Powers - Internal MedicineNick D Gansemer - Internal MedicineDavid K Meyerholz - PathologyMichael J Welsh - Molecular Physiology and BiophysicsDavid A Stoltz - Internal MedicinePatrick L Sinn - Pediatrics, The University of Iowa, Iowa City, Iowa, USAPaul B McCray Jr - Pediatrics, The University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.1(14), e88730
- Publisher
- United States
- DOI
- 10.1172/jci.insight.88730
- PMID
- 27656681
- PMCID
- PMC5027966
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Grant note
- P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS R01 HL105821 / NHLBI NIH HHS T32 GM007337 / NIGMS NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS T32 AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 09/08/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020787902771
Metrics
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