ArticlePloS one2011
Common gene therapy viral vectors do not efficiently penetrate sputum from cystic fibrosis patients.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
42 citing papers in PubMed, 73 citations in OpenAlex.
- Chronic lung infection does not impair lentiviral vector gene transfer in a cystic fibrosis rat model.Gene therapy · 2026Article
- Micro/nanoscale bubble-mediated mucolytic conditioning of the lung model of cystic fibrosis enhances nanoparticle transport through the mucus.Biomaterials · 2026Article
- Inhalable gene and RNA therapy for cystic fibrosis: perspectives and progress in clinical development.Nanomedicine (London, England) · 2026Review
- Recent strategies for enhanced delivery of mRNA to the lungs.Nanomedicine (London, England) · 2025Review
- Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.Current gene therapy · 2025Review
- A noval noninvasive targeted therapy for osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated SPIO/TP53/PLGA nanobubble.Frontiers in bioengineering and biotechnology · 2024Article
- Effective viral-mediated lung gene therapy: is airway surface preparation necessary?Gene therapy · 2023Review
- Biomaterials for intranasal and inhaled vaccine delivery.Nature reviews bioengineering · 2023Article
- Physiology and pathophysiology of human airway mucus.Physiological reviews · 2022Review
- Article
- Mucus-targeting therapies of defective mucus clearance for cystic fibrosis: A short review.Current opinion in pharmacology · 2022Review
- Improved in-vivo airway gene transfer via magnetic-guidance, with protocol development informed by synchrotron imaging.Scientific reports · 2022Article
- Tissue and cell-type-specific transduction using rAAV vectors in lung diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Inhaled aerosols: Their role in COVID-19 transmission, including biophysical interactions in the lungs.Current opinion in colloid & interface science · 2021Review
- Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy.Cell & bioscience · 2021Review
- Avoiding a Sticky Situation: Bypassing the Mucus Barrier for Improved Local Drug Delivery.Trends in molecular medicine · 2021Review
- Strategy to enhance dendritic cell-mediated DNA vaccination in the lung.Advanced therapeutics · 2021Article
- Optimizations of In Vitro Mucus and Cell Culture Models to Better Predict In Vivo Gene Transfer in Pathological Lung Respiratory Airways: Cystic Fibrosis as an Example.Pharmaceutics · 2020Review
- New Directions in Pulmonary Gene Therapy.Human gene therapy · 2020Review
- The Cystic Fibrosis-Like Airway Surface Layer Is not a Significant Barrier for Delivery of Eluforsen to Airway Epithelial Cells.Journal of aerosol medicine and pulmonary drug delivery · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Norwalk virus and human papilloma virus, two viruses that infect humans at mucosal surfaces, have been found capable of rapidly penetrating human mucus secretions. Viral vectors for gene therapy of Cystic Fibrosis (CF) must similarly penetrate purulent lung airway mucus (sputum) to deliver DNA to airway epithelial cells. However, surprisingly little is known about the rates at which gene delivery vehicles penetrate sputum, including viral vectors used in clinical trials for CF gene therapy. We find that sputum spontaneously expectorated by CF patients efficiently traps two viral vectors commonly used in CF gene therapy trials, adenovirus (d∼80 nm) and adeno-associated virus (AAV serotype 5; d∼20 nm), leading to average effective diffusivities that are ∼3,000-fold and 12,000-fold slower than their theoretical speeds in water, respectively. Both viral vectors are slowed by adhesion, as engineered muco-inert nanoparticles with diameters as large as 200 nm penetrate the same sputum samples at rates only ∼40-fold reduced compared to in pure water. A limited fraction of AAV exhibit sufficiently fast mobility to penetrate physiologically thick sputum layers, likely because of the lower viscous drag and smaller surface area for adhesion to sputum constituents. Nevertheless, poor penetration of CF sputum is likely a major contributor to the ineffectiveness of viral vector based gene therapy in the lungs of CF patients observed to date.
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What OpenQuestion holds
Registered trials
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.