ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Systematic comparison of rAAV vectors manufactured using large-scale suspension cultures of Sf9 and HEK293 cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
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- Continuous production of recombinant adeno-associated virus in the insect cell/baculovirus expression vector system.Molecular therapy. Advances · 2026Article
- Engineering challenges and translational opportunities in emerging gene delivery platforms.Nature biomedical engineering · 2026Review
- An Improved Method for Determining the Infection Titer of Replication-Competent Adeno-Associated Virus.Biomedicines · 2026Article
- Manufacture of adeno-associated virus vectors by a novel human-derived cell line HAT and comprehensive evaluation of the vectors.Molecular therapy. Advances · 2026Article
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Species barriers in AAV tropism: mechanisms, models, and emerging solutions for clinical translation.Acta biochimica Polonica · 2026Review
- A novel gene therapy platform for the treatment of type 2 diabetes and obesity.Molecular therapy. Nucleic acids · 2025Article
- Advances in Serum-Free Suspension Culture Technology for Animal Cells and Their Applications.Vaccines · 2025Review
- Insect cell expression system: advances in applications, engineering strategies, and bioprocess development.Journal of biological engineering · 2025Review
- AAV-Based Gene Therapy: Opportunities, Risks, and Scale-Up Strategies.International journal of molecular sciences · 2025Review
- Insights into Adeno-Associated Virus Capsid Charge Heterogeneity.Analytical chemistry · 2025Article
- A clinician's guide to AAV production - How manufacturing platforms shape vector properties.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Perfusion-Based Production of rAAV via an Intensified Transient Transfection Process.Biotechnology and bioengineering · 2025Article
- Combination of hydrophilic interaction liquid chromatography and top-down mass spectrometry for characterisation of adeno-associated virus capsid proteins.Analytical and bioanalytical chemistry · 2025Article
- Preclinical evaluation of AAV9-coSMN1 gene therapy for spinal muscular atrophy: efficacy and safety in mouse models and non-human primates.Molecular medicine (Cambridge, Mass.) · 2025Article
- Construction and Expression of Fc-FGF21 by Different Expression Systems and Comparison of Their Similarity and Difference with Efruxifermin by In Vitro and In Vivo Studies.Applied biochemistry and biotechnology · 2025Article
- Impact of multiplicity of infection and baculovirus co-infection ratio on recombinant adeno-associated virus vector production in insect cells.Frontiers in bioengineering and biotechnology · 2025Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant adeno-associated virus (rAAV) vectors could be manufactured by plasmid transfection into human embryonic kidney 293 (HEK293) cells or baculovirus infection of Spodoptera frugiperda (Sf9) insect cells. However, systematic comparisons between these systems using large-scale, high-quality AAV vectors are lacking. rAAV from Sf9 cells (Sf9-rAAV) at 2-50 L and HEK293 cells (HEK-rAAV) at 2-200 L scales were characterized. HEK-rAAV had ∼40-fold lower yields but ∼10-fold more host cell DNA measured by droplet digital PCR and next-generation sequencing, respectively. The electron microscope observed a lower full/empty capsid ratio in HEK-rAAV (70.8%) than Sf9-rAAV (93.2%), while dynamic light scattering and high-performance liquid chromatography analysis showed that HEK-rAAV had more aggregation. Liquid chromatography tandem mass spectrometry identified different post-translational modification profiles between Sf9-rAAV and HEK-rAAV. Furthermore, Sf9-rAAV had a higher tissue culture infectious dose/viral genome than HEK-rAAV, indicating better infectivity. Additionally, Sf9-rAAV achieved higher in vitro transgene expression, as measured by ELISA. Finally, after intravitreal dosing into a mouse laser choroidal neovascularization model, Sf9-rAAV and HEK-rAAV achieved similar efficacy. Overall, this study detected notable differences in the physiochemical characteristics of HEK-rAAV and Sf9-rAAV. However, the in vitro and in vivo biological functions of the rAAV from these systems were highly comparable. Sf9-rAAV may be preferred over HEK293-rAAV for advantages in yields, full/empty ratio, scalability, and cost.
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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.