ArticlePLoS biology2009
CFTR delivery to 25% of surface epithelial cells restores normal rates of mucus transport to human cystic fibrosis airway epithelium.
Article in PLoS biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
115 citing papers in PubMed, 2 syntheses or guidelines pooled it, 188 citations in OpenAlex.
- CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Pooled it
- Nebuliser systems for drug delivery in cystic fibrosis.The Cochrane database of systematic reviews · 2023Pooled it
- RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction.The Journal of clinical investigation · 2014Trial
- Trial
- Article
- Review
- Extracellular vesicle-based delivery to airway basal cells for durable gene therapy in cystic fibrosis.Frontiers in bioengineering and biotechnology · 2026Review
- Exploring the deletion landscape ofbioRxiv : the preprint server for biology · 2025Article
- Novel Cystic Fibrosis Ferret Model Enables Visualization of CFTR Expression Cells and Genetic CFTR Reactivation.Human gene therapy · 2025Article
- ACE-tRNAs are a platform technology for suppressing nonsense mutations that cause cystic fibrosis.Nucleic acids research · 2025Article
- Pharmacological and pre-clinical safety profile of rSIV.F/HN, a hybrid lentiviral vector for cystic fibrosis gene therapy.The European respiratory journal · 2025Article
- Mechanism of Genome Editing Tools and Their Application on Genetic Inheritance Disorders.Global medical genetics · 2024Review
- CFTR expression decreases with age in several airway cell types.Scientific reports · 2024Article
- Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein.Scientific reports · 2024Article
- Durable transgene expression and efficient re-administration after rAAV2.5T-mediated fCFTRΔR gene delivery to adult ferret lungs.Molecular therapy. Methods & clinical development · 2024Article
- Synonymous Mutations Can Alter Protein Dimerization Through Localized Interface Misfolding Involving Self-entanglements.Journal of molecular biology · 2024Article
- Viral airway injury promotes cell engraftment in an in vitro model of cystic fibrosis cell therapy.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Current landscape of cystic fibrosis gene therapy.Frontiers in pharmacology · 2024Review
- Molecular and functional correction of a deep intronic splicing mutation inMolecular therapy. Methods & clinical development · 2023Article
- Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Dysfunction of CFTR in cystic fibrosis (CF) airway epithelium perturbs the normal regulation of ion transport, leading to a reduced volume of airway surface liquid (ASL), mucus dehydration, decreased mucus transport, and mucus plugging of the airways. CFTR is normally expressed in ciliated epithelial cells of the surface and submucosal gland ductal epithelium and submucosal gland acinar cells. Critical questions for the development of gene transfer strategies for CF airway disease are what airway regions require CFTR function and how many epithelial cells require CFTR expression to restore normal ASL volume regulation and mucus transport to CF airway epithelium? An in vitro model of human CF ciliated surface airway epithelium (CF HAE) was used to test whether a human parainfluenza virus (PIV) vector engineered to express CFTR (PIVCFTR) could deliver sufficient CFTR to CF HAE to restore mucus transport, thus correcting the CF phenotype. PIVCFTR delivered CFTR to >60% of airway surface epithelial cells and expressed CFTR protein in CF HAE approximately 100-fold over endogenous levels in non-CF HAE. This efficiency of CFTR delivery fully corrected the basic bioelectric defects of Cl(-) and Na(+) epithelial ion transport and restored ASL volume regulation and mucus transport to levels approaching those of non-CF HAE. To determine the numbers of CF HAE surface epithelial cells required to express CFTR for restoration of mucus transport to normal levels, different amounts of PIVCFTR were used to express CFTR in 3%-65% of the surface epithelial cells of CF HAE and correlated to increasing ASL volumes and mucus transport rates. These data demonstrate for the first time, to our knowledge, that restoration of normal mucus transport rates in CF HAE was achieved after CFTR delivery to 25% of surface epithelial cells. In vivo experimentation in appropriate models will be required to determine what level of mucus transport will afford clinical benefit to CF patients, but we predict that a future goal for corrective gene transfer to the CF human airways in vivo would attempt to target at least 25% of surface epithelial cells to achieve mucus transport rates comparable to those in non-CF airways.
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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.