ArticleNature communications2022
Self-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contamination.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Integrated Continuous Biomanufacturing of Recombinant Adeno-Associated Virus.bioRxiv : the preprint server for biology · 2026Article
- Viral gene replication enhances AAV vector quality and reduces manufacturing costs.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- B Lymphocyte Protein Factories produced by Hematopoietic Stem Cell Gene Editing.bioRxiv : the preprint server for biology · 2026Article
- Characterization and quantitation of baculoviral DNA in rAAV vectors produced in Sf9 cells.Molecular therapy. Methods & clinical development · 2025Article
- A two-pass anion-exchange chromatography strategy for enrichment of full capsids in manufacturing of adeno-associated viral vectors.Molecular therapy. Methods & clinical development · 2025Article
- Self-silencing adenovirus enables precise infectious titration of recombinant adeno-associated viral vectors.Molecular therapy. Methods & clinical development · 2025Article
- AAVone: A cost-effective, single-plasmid solution for efficient AAV production with reduced DNA impurities.Molecular therapy. Nucleic acids · 2025Article
- Polo-like kinase inhibitors increase AAV production by halting cell cycle progression.Molecular therapy. Methods & clinical development · 2025Article
- Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases.International journal of molecular sciences · 2025Review
- Improved Recombinant Adeno-Associated Viral Vector Production via Molecular Evolution of the Viral Rep Protein.International journal of molecular sciences · 2025Article
- Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.Current gene therapy · 2025Review
- Production of recombinant adeno-associated virus 5 using a novel self-attenuating adenovirus production platform.Molecular therapy. Methods & clinical development · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- Advanced gene therapy system for the treatment of solid tumour: A review.Materials today. Bio · 2024Review
- Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.Molecular therapy. Methods & clinical development · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Development of Stable Packaging and Producer Cell Lines for the Production of AAV Vectors.Microorganisms · 2024Review
- A Novel Role for the Adenovirus L4 Region 22K and 33K Proteins in Adeno-Associated Virus Production.Human gene therapy · 2024Article
- PCR-based analytics of gene therapies using adeno-associated virus vectors: Considerations for cGMP method development.Molecular therapy. Methods & clinical development · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) shows great promise for gene therapy, however scalability, yield and quality remain significant issues. Here we describe an rAAV manufacturing strategy using a 'helper' adenovirus that self-inhibits its major late promoter (MLP) to truncate its own replication. Inserting a tetracycline repressor (TetR) binding site into the MLP and encoding the TetR under its transcriptional control allowed normal adenovirus replication in the presence of doxycycline but only genome amplification and early gene expression (the 'helper' functions) in its absence. Using this self-inhibiting adenovirus we demonstrate delivery of adenoviral helper functions, AAV rep and cap genes, and the rAAV genome to yield up to 30-fold more rAAV vectors compared to the helper-free plasmid approach and significant improvements in particle infectivity for a range of serotypes. This system allows significant improvements in the production of serotypes rAAV2, rAAV6, rAAV8 and rAAV9, and enables propagation of existing rAAV without transfection, a process that improves batch quality by depleting reverse packaged DNA contaminants. We propose this as a high-yielding, contaminant-free system suitable for scalable rAAV manufacture.
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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.