ArticleProceedings of the National Academy of Sciences of the United States of America1998
Efficient expression of CFTR function with adeno-associated virus vectors that carry shortened CFTR genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 74 citations in OpenAlex.
- Theoretical Models and Simulations of Gene Delivery with Polyurethane: The Importance of Polyurethane as a Vector in Personalized Therapy.Biomedicines · 2025Article
- The predawn dilemma in adeno-associated virus-based gene therapies for hereditary deafness.American journal of stem cells · 2025Review
- Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.bioRxiv : the preprint server for biology · 2024Article
- Current landscape of cystic fibrosis gene therapy.Frontiers in pharmacology · 2024Review
- Gene therapy for cystic fibrosis: Challenges and prospects.Frontiers in pharmacology · 2022Review
- Viral Vectors, Animal Models, and Cellular Targets for Gene Therapy of Cystic Fibrosis Lung Disease.Human gene therapy · 2020Review
- CRISPR/Cas Applications in Myotonic Dystrophy: Expanding Opportunities.International journal of molecular sciences · 2019Review
- Review
- Human Bocavirus Type-1 Capsid Facilitates the Transduction of Ferret Airways by Adeno-Associated Virus Genomes.Human gene therapy · 2017Article
- Optimization of Recombinant Adeno-Associated Virus-Mediated Expression for Large Transgenes, Using a Synthetic Promoter and Tandem Array Enhancers.Human gene therapy · 2015Article
- Ferret and pig models of cystic fibrosis: prospects and promise for gene therapy.Human gene therapy. Clinical development · 2015Review
- A novel chimeric adenoassociated virus 2/human bocavirus 1 parvovirus vector efficiently transduces human airway epithelia.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Gene therapy for the treatment of cystic fibrosis.The application of clinical genetics · 2012Article
- Cystic fibrosis transmembrane conductance regulator with a shortened R domain rescues the intestinal phenotype of CFTR-/- mice.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Cystic fibrosis: exploiting its genetic basis in the hunt for new therapies.Pharmacology & therapeutics · 2010Review
- Generation of novel AAV variants by directed evolution for improved CFTR delivery to human ciliated airway epithelium.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Functional cystic fibrosis transmembrane conductance regulator expression in cystic fibrosis airway epithelial cells by AAV6.2-mediated segmental trans-splicing.Human gene therapy · 2009Article
- Protein trans-splicing as a means for viral vector-mediated in vivo gene therapy.Human gene therapy · 2008Article
- Packaging capacity of adeno-associated virus serotypes: impact of larger genomes on infectivity and postentry steps.Journal of virology · 2005Article
- Novel molecular approaches to cystic fibrosis gene therapy.The Biochemical journal · 2005Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Adeno-associated virus (AAV)-based vectors have been shown to be effective in transferring the cystic fibrosis gene (CFTR) into airway epithelial cells in animal models and in patients. However, the level of CFTR gene expression has been low because the vector cannot accommodate the CFTR gene together with a promoter. In this study, we described a strategy to reduce the size of the CFTR cDNA to allow the incorporation of an effective promoter with the CFTR gene into AAV vectors. We engineered and tested 20 CFTR mini-genes containing deletions that were targeted to regions that may contain nonessential sequences. Functional analyses showed that four of the shortened CFTRs (one with combined deletions) retained the function and the characteristics of a wild-type CFTR, as measured by open probability, time voltage dependence, and regulation by cAMP. By using an AAV vector with a P5 promoter, we transduced these short forms of CFTR genes into target cells and demonstrated high levels of CFTR expression. We also demonstrated that smaller AAV/CFTR vectors with a P5 promoter expressed the CFTR gene more efficiently than larger vectors or a vector in which CFTR gene was expressed from the AAV inverted terminal repeat sequence. The CFTR mini-gene with combined deletions was packaged into AAV virions more efficiently, generated higher titers of transducing virions, and more effectively transferred CFTR function into target cells. These new vectors should circumvent the limitations of AAV vector for CFTR expression. Our strategy also may be applicable to other genes, the sizes of which exceed the packaging limit of an AAV vector.
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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.