ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Generation of novel AAV variants by directed evolution for improved CFTR delivery to human ciliated airway epithelium.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 83 citations in OpenAlex.
- Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Trial
- Optimized AAV capsids robustly transduce airway epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- Recent strategies for enhanced delivery of mRNA to the lungs.Nanomedicine (London, England) · 2025Review
- Discovery of peptides for ligand-mediated delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia.Molecular therapy. Nucleic acids · 2024Article
- Enhanced transgene expression from single-stranded AAV vectors in human cellsMolecular therapy. Nucleic acids · 2024Article
- Development of AAV-Mediated Gene Therapy Approaches to Treat Skeletal Diseases.Human gene therapy · 2024Review
- Gene Therapy for Genetic Syndromes: Understanding the Current State to Guide Future Care.Biotech (Basel (Switzerland)) · 2024Review
- Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.Nature protocols · 2023Review
- CRISPR/Cas9 Genome Editing for Tissue-Specific In Vivo Targeting: Nanomaterials and Translational Perspective.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Rationale and strategies for the development of safe and effective optimized AAV vectors for human gene therapy.Molecular therapy. Nucleic acids · 2023Review
- RNA editing: Expanding the potential of RNA therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Recombinant Adeno-Associated Viral Vector-Mediated Gene Transfer ofInternational journal of molecular sciences · 2022Article
- SANA: cross-species prediction of Gene Ontology GO annotations via topological network alignment.NPJ systems biology and applications · 2022Article
- Preventing packaging of translatable P5-associated DNA contaminants in recombinant AAV vector preps.Molecular therapy. Methods & clinical development · 2022Article
- Tissue and cell-type-specific transduction using rAAV vectors in lung diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Transduction of Pig Small Airway Epithelial Cells and Distal Lung Progenitor Cells by AAV4.Cells · 2021Article
- Correction of Airway Stem Cells: Genome Editing Approaches for the Treatment of Cystic Fibrosis.Human gene therapy · 2020Review
- Translating CRISPR-Cas Therapeutics: Approaches and Challenges.The CRISPR journal · 2020Review
- The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses.Frontiers in microbiology · 2020Review
- Recombinant Adeno-Associated Virus Gene Therapy in Light of Luxturna (and Zolgensma and Glybera): Where Are We, and How Did We Get Here?Annual review of virology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (AAV) vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been used to deliver CFTR to the airway epithelium of cystic fibrosis (CF) patients. However, no significant CFTR function has been demonstrated likely due to low transduction efficiencies of the AAV vectors. To improve AAV transduction efficiency for human airway epithelium (HAE), we generated a chimeric AAV library and performed directed evolution of AAV on an in vitro model of human ciliated airway epithelium. Two independent and novel AAV variants were identified that contained capsid components from AAV-1, AAV-6, and/or AAV-9. The transduction efficiencies of the two novel AAV variants for human ciliated airway epithelium were three times higher than that for AAV-6. The novel variants were then used to deliver CFTR to ciliated airway epithelium from CF patients. Here we show that our novel AAV variants, but not the parental, AAV provide sufficient CFTR delivery to correct the chloride ion transport defect to ~25% levels measured in non-CF cells. These results suggest that directed evolution of AAV on relevant in vitro models will enable further improvements in CFTR gene transfer efficiency and the development of an efficacious and safe gene transfer vector for CF lung disease.
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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.