ArticleProceedings of the National Academy of Sciences of the United States of America2002
CFTR with a partially deleted R domain corrects the cystic fibrosis chloride transport defect in human airway epithelia in vitro and in mouse nasal mucosa in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- Optimized AAV capsids robustly transduce airway epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- Inhalable gene and RNA therapy for cystic fibrosis: perspectives and progress in clinical development.Nanomedicine (London, England) · 2026Review
- Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-in-Human Trial.American journal of respiratory and critical care medicine · 2024Review
- In vivo editing of lung stem cells for durable gene correction in mice.Science (New York, N.Y.) · 2024Article
- Current landscape of cystic fibrosis gene therapy.Frontiers in pharmacology · 2024Review
- Progress in Respiratory Gene Therapy.Human gene therapy · 2022Review
- Targeted replacement of full-length CFTR in human airway stem cells by CRISPR-Cas9 for pan-mutation correction in the endogenous locus.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Gene therapy for cystic fibrosis: Challenges and prospects.Frontiers in pharmacology · 2022Review
- Clinical and molecular characterization of the R751L-CFTR mutation.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- New Directions in Pulmonary Gene Therapy.Human gene therapy · 2020Review
- Viral Vectors, Animal Models, and Cellular Targets for Gene Therapy of Cystic Fibrosis Lung Disease.Human gene therapy · 2020Review
- A Novel AAV-mediated Gene Delivery System Corrects CFTR Function in Pigs.American journal of respiratory cell and molecular biology · 2019Article
- Unravelling the Regions of Mutant F508del-CFTR More Susceptible to the Action of Four Cystic Fibrosis Correctors.International journal of molecular sciences · 2019Article
- Review
- Lentiviral-mediated phenotypic correction of cystic fibrosis pigs.JCI insight · 2016Article
- Optimization of Recombinant Adeno-Associated Virus-Mediated Expression for Large Transgenes, Using a Synthetic Promoter and Tandem Array Enhancers.Human gene therapy · 2015Article
- Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.The Journal of biological chemistry · 2015Article
- A novel gene delivery method transduces porcine pancreatic duct epithelial cells.Gene therapy · 2014Article
- Use of kinase inhibitors to correct ΔF508-CFTR function.Molecular & cellular proteomics : MCP · 2012Article
- Bovine AAV transcytosis inhibition by tannic acid results in functional expression of CFTR in vitro and altered biodistribution in vivo.Gene therapy · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
In developing gene therapy for cystic fibrosis (CF) airways disease, a transgene encoding a partially deleted CF transmembrane conductance regulator (CFTR) Cl- channel could be of value for vectors such as adeno-associated virus that have a limited packaging capacity. Earlier studies in heterologous cells indicated that the CFTR R (regulatory) domain is predominantly random coil and that parts of the R domain can be deleted without abolishing channel function. Therefore, we designed a series of CFTR variants with shortened R domains (between residues 708 and 835) and expressed them in well-differentiated cultures of CF airway epithelia. All of the variants showed normal targeting to the apical membrane, and for the constructs we tested, biosynthesis was like wild type. Moreover, all constructs generated transepithelial Cl- current in CF epithelia. Comparison of the Cl- transport suggested that the length of the R domain, the presence of phosphorylation sites, and other factors contribute to channel activity. A variant deleting residues 708-759 complemented CF airway epithelia to the same extent as wild-type CFTR and showed no current in the absence of cAMP stimulation. In addition, expression in nasal mucosa of CF mice corrected the Cl- transport defect. These data provide insight into the structure and function of the R domain and identify regions that can be deleted with retention of function. Thus they suggest a strategy for shortening the transgene used in CF gene therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.