ArticleProceedings of the National Academy of Sciences of the United States of America2005
A shortened adeno-associated virus expression cassette for CFTR gene transfer to cystic fibrosis airway epithelia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Double-stranded DNA donors and CRISPR-Cas9 for universal correction of mutations causing cystic fibrosis in human airway cells.Molecular therapy. Nucleic acids · 2026Article
- Optimized AAV capsids robustly transduce airway epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- Recombinant Adeno-Associated Virus Vector Mediated Gene Editing in Proliferating and Polarized Cultures of Human Airway Epithelial Cells.Human gene therapy · 2025Article
- Optimized gene transduction in human lung organoids: A high-efficiency method for advanced research applications.Communications biology · 2025Article
- The predawn dilemma in adeno-associated virus-based gene therapies for hereditary deafness.American journal of stem cells · 2025Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
- Critical role of TPRN rings in the stereocilia for hearing.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Current landscape of cystic fibrosis gene therapy.Frontiers in pharmacology · 2024Review
- Identification of host essential factors for recombinant AAV transduction of the polarized human airway epithelium.Journal of virology · 2023Article
- Immunosuppression reduces rAAV2.5T neutralizing antibodies that limit efficacy following repeat dosing to ferret lungs.Molecular therapy. Methods & clinical development · 2023Article
- Reciprocal mutations of lung-tropic AAV capsids lead to improved transduction properties.Frontiers in genome editing · 2023Article
- Co-transduction of dual-adeno-associated virus vectors in the neonatal and adult mouse utricles.Frontiers in molecular neuroscience · 2022Article
- Transduction of Pig Small Airway Epithelial Cells and Distal Lung Progenitor Cells by AAV4.Cells · 2021Article
- Repeat Dosing of AAV2.5T to Ferret Lungs Elicits an Antibody Response That Diminishes Transduction in an Age-Dependent Manner.Molecular therapy. Methods & clinical development · 2020Article
- New Directions in Pulmonary Gene Therapy.Human gene therapy · 2020Review
- Protection against SIV in Rhesus Macaques Using Albumin and CD4-Based Vector-Mediated Gene Transfer.Molecular therapy. Methods & clinical development · 2020Article
- Viral Vectors, Animal Models, and Cellular Targets for Gene Therapy of Cystic Fibrosis Lung Disease.Human gene therapy · 2020Review
- Advances in gene therapy for cystic fibrosis lung disease.Human molecular genetics · 2019Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Adeno-associated viruses (AAVs) such as AAV5 that transduce airway epithelia from the apical surface are attractive vectors for gene transfer in cystic fibrosis (CF). However, their utility in CF has been limited because packaging of the insert becomes inefficient when its length exceeds approximately 4,900-5,000 bp. To partially circumvent this size constraint, we previously developed a CF transmembrane conductance regulator (CFTR) transgene that deleted a portion of the R domain (CFTRDeltaR). In this study, we focused on shortening the other elements in the AAV expression cassette. We found that portions of the CMV immediate/early (CMVie) enhancer/promoter could be deleted without abolishing activity. We also tested various intervening sequences, poly(A) signals, and an intron to develop an expression cassette that meets the size restrictions imposed by AAV. We then packaged these shortened elements with the CFTRDeltaR transgene into AAV5 and applied them to the apical surface of differentiated CF airway epithelia. Two to 4 weeks later, the AAV5 vectors partially corrected the CF Cl(-) transport defect. These results demonstrate that a single AAV vector can complement the CF defect in differentiated airway epithelia and thereby further the development of effective CF gene transfer.
Indexed as
Identifiers
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.