ArticleMolecular therapy. Methods & clinical development2021
Mechanistic model for production of recombinant adeno-associated virus via triple transfection of HEK293 cells.
Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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.
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Who cites it
47 citing papers in PubMed, 97 citations in OpenAlex.
- AAV vector production in suspension cells using PEI transfection and sodium butyrate with orthogonal assessment of function and quality.Molecular therapy. Advances · 2026Article
- Mechanistic model for HEK293 viral vector processes and its application in a digital shadow framework.Bioprocess and biosystems engineering · 2026Article
- Rational engineering of an antifreeze-based biomaterial with dual-enhanced ice-binding and delivery for high-efficiency cryopreservation.Journal of advanced research · 2026Article
- Combined Plasmid Redesign and Transfection Optimization Significantly Increases Upstream AAV Titers While Maintaining Vector Quality and In Vivo Potency.Microorganisms · 2026Article
- Anion-Exchange Membrane Chromatography for the Separation of Empty and Full Adeno-Associated Viral Capsids.Biotechnology journal · 2026Article
- Backbone-Minimised Nanoplasmid DNA Systems Enable High-Titre AAV Production in Suspension HEK293 Platforms.Pharmaceutics · 2026Article
- Enhanced AAV production via rational design of a novel pHelper vector integrated with HSV-1 helper genes.Synthetic and systems biotechnology · 2026Article
- AAV Assembled Capsids Are Produced in Cells Blocked From Cell Cycle Progression.Biotechnology and bioengineering · 2026Article
- Imaged Capillary Isoelectric Focusing (icIEF) Platform for Characterization of Charge Variants of Adeno-Associated Virus (AAV) Capsids and Impact on their Transduction Efficiency.Current gene therapy · 2026Article
- Directed evolution of liver-detargeted AAV vectors for systemic gene delivery to skeletal muscle and heart.Molecular therapy. Methods & clinical development · 2025Article
- Chronologically distributed transfection improves AAV2 and AAV2/8 capsid filling and reveals assembly schedule divergence.Molecular therapy. Methods & clinical development · 2025Article
- Mammalian synthetic gene circuits for biopharmaceutical development & manufacture.NPJ systems biology and applications · 2025Review
- Heterogeneity in an adeno-associated virus transfection-based production process limits the production efficiency.Scientific reports · 2025Article
- A clinician's guide to AAV production - How manufacturing platforms shape vector properties.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Development of an HEK293 Suspension Cell Culture Medium, Transient Transfection Optimization Workflow, and Analytics for Batch rAAV Manufacturing.Biotechnology and bioengineering · 2025Article
- Self-silencing adenovirus enables precise infectious titration of recombinant adeno-associated viral vectors.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
- AAVone: A cost-effective, single-plasmid solution for efficient AAV production with reduced DNA impurities.Molecular therapy. Nucleic acids · 2025Article
- An Integrated Experimental and Modeling Approach for Crystallization of Complex Biotherapeutics.Crystal growth & design · 2025Article
- Perfusion-Based Production of rAAV via an Intensified Transient Transfection Process.Biotechnology and bioengineering · 2025Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Manufacturing of recombinant adeno-associated virus (rAAV) viral vectors remains challenging, with low yields and low full:empty capsid ratios in the harvest. To elucidate the dynamics of recombinant viral production, we develop a mechanistic model for the synthesis of rAAV viral vectors by triple plasmid transfection based on the underlying biological processes derived from wild-type AAV. The model covers major steps starting from exogenous DNA delivery to the reaction cascade that forms viral proteins and DNA, which subsequently result in filled capsids, and the complex functions of the Rep protein as a regulator of the packaging plasmid gene expression and a catalyst for viral DNA packaging. We estimate kinetic parameters using dynamic data from literature and in-house triple transient transfection experiments. Model predictions of productivity changes as a result of the varied input plasmid ratio are benchmarked against transfection data from the literature. Sensitivity analysis suggests that (1) the poorly coordinated timeline of capsid synthesis and viral DNA replication results in a low ratio of full virions in harvest, and (2) repressive function of the Rep protein could be impeding capsid production at a later phase. The analyses from the mathematical model provide testable hypotheses for evaluation and reveal potential process bottlenecks that can be investigated.
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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 Socratic graph.