ArticleProceedings of the National Academy of Sciences of the United States of America2009
An inducible system for highly efficient production of recombinant adeno-associated virus (rAAV) vectors in insect Sf9 cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Engineering inter-promoter spacing in baculovirus dual-expression systems enhances transcription and reduces rAAV2 empty capsids.Molecular therapy. Advances · 2026Article
- Rational engineering of the P5 TRS-mimic site and REP78/68 start codon yields promoter variants that improve rAAV purity while maintaining high titers.Molecular therapy. Advances · 2026Article
- Characterization and quantitation of baculoviral DNA in rAAV vectors produced in Sf9 cells.Molecular therapy. Methods & clinical development · 2025Article
- Consecutive Affinity and Ion-Exchange Chromatography for AAV9 Vectors Purification.Biomedicines · 2025Article
- Recent Advances in Therapeutics and Manufacturing Processes of Recombinant Adeno-Associated Virus for the Treatment of Lung Diseases.Current gene therapy · 2025Review
- Temporal insights into molecular and cellular responses during rAAV production in HEK293T cells.Molecular therapy. Methods & clinical development · 2024Article
- A robust and flexible baculovirus-insect cell system for AAV vector production with improved yield, capsid ratios and potency.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
- Systematic comparison of rAAV vectors manufactured using large-scale suspension cultures of Sf9 and HEK293 cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Functional Baculovirus Particle Quantification via Plaque Assay.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Recombinant AAV Production.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Amyloid precursor protein facilitates SARS-CoV-2 virus entry into cells and enhances amyloid-β-associated pathology in APP/PS1 mouse model of Alzheimer's disease.Translational psychiatry · 2023Article
- Stowaways in the cargo: Contaminating nucleic acids in rAAV preparations for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Article
- High-Level rAAV Vector Production by rAdV-Mediated Amplification of Small Amounts of Input Vector.Viruses · 2022Article
- Development of an insect cell-based adeno-associated virus packaging cell line employing advancedMolecular therapy. Methods & clinical development · 2022Article
- Monobac System-A Single Baculovirus for the Production of rAAV.Microorganisms · 2021Article
- Methods Matter: Standard Production Platforms for Recombinant AAV Produce Chemically and Functionally Distinct Vectors.Molecular therapy. Methods & clinical development · 2020Article
- Article
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Authors and funding
3 authors.
Funding
Abstract
Production of clinical-grade gene therapy vectors for human trials remains a major hurdle in advancing cures for a number of otherwise incurable diseases. We describe a system based on a stably transformed insect cell lines harboring helper genes required for vector production. Integrated genes remain silent until the cell is infected with a single baculovirus expression vector (BEV). The induction of expression results from a combination of the amplification of integrated resident genes (up to 1,200 copies per cell) and the enhancement of the expression mediated by the immediate-early trans-regulator 1 (IE-1) encoded by BEV. The integration cassette incorporates an IE-1 binding target sequence from wild-type Autographa californica multiple nuclear polyhedrosis virus, a homologous region 2 (hr2). A feed-forward loop is initiated by one of the induced proteins, Rep78, boosting the amplification of the integrated genes. The system was tested for the coordinated expression of 7 proteins required to package recombinant adeno-associated virus (rAAV)2 and rAAV1. The described arrangement provided high levels of Rep and Cap proteins, thus improving rAAV yield by 10-fold as compared with the previously described baculovirus/rAAV production system.
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