ArticleMolecular therapy. Methods & clinical development2023
Production of rAAV by plasmid transfection induces antiviral and inflammatory responses in suspension HEK293 cells.
Article in Molecular therapy. Methods & clinical development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
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Who cites it
25 citing papers in PubMed, 41 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
- Comparative Transcriptomic Profiling Reveals Differences in Initiation of Antiviral Response in Low rAAV Producing HEK293 Suspension Cells.Biotechnology journal · 2026Article
- Comparative Analysis of rAAV Production from Plasmid-Encoded Versus Chromosomally Integrated rAAV Transgene in HEK293 Cells.International journal of molecular sciences · 2026Article
- AAV Assembled Capsids Are Produced in Cells Blocked From Cell Cycle Progression.Biotechnology and bioengineering · 2026Article
- Chronologically distributed transfection improves AAV2 and AAV2/8 capsid filling and reveals assembly schedule divergence.Molecular therapy. Methods & clinical development · 2025Article
- Heterogeneity in an adeno-associated virus transfection-based production process limits the production efficiency.Scientific reports · 2025Article
- Unveiling Small Non-Coding RNA Dynamics During Recombinant Adeno-Associated Virus Production.Biotechnology journal · 2025Article
- Optimization of YF17D-Vectored Zika Vaccine Production by Employing Small-Molecule Viral Sensitizers to Enhance Yields.Vaccines · 2025Article
- Development of an HEK293 Suspension Cell Culture Medium, Transient Transfection Optimization Workflow, and Analytics for Batch rAAV Manufacturing.Biotechnology and bioengineering · 2025Article
- Nuclear Fraction Proteome Analyses During rAAV Production of AAV2-Plasmid-Transfected HEK-293 Cells.International journal of molecular sciences · 2025Article
- AAVone: A cost-effective, single-plasmid solution for efficient AAV production with reduced DNA impurities.Molecular therapy. Nucleic acids · 2025Article
- CRISPR screen reveals modifiers of rAAV production including known rAAV infection genes playing an unexpected role in vector production.Molecular therapy. Methods & clinical development · 2025Article
- Polo-like kinase inhibitors increase AAV production by halting cell cycle progression.Molecular therapy. Methods & clinical development · 2025Article
- Unlocking the Puzzle of Mammalian Transfection: The Role of the RNA-sensing-Mediated Interferon Response in the Cellular Defense Against Foreign DNA Intrusion.International journal of biological sciences · 2025Article
- Transcriptomics-informed pharmacology identifies epigenetic and cell cycle regulators that enhance AAV production.Molecular therapy. Methods & clinical development · 2024Article
- E2A, VA RNA I, and L4-22k adenoviral helper genes are sufficient for AAV production in HEK293 cells.Molecular therapy. Methods & clinical development · 2024Article
- CRISPR screen for rAAV production implicates genes associated with infection.bioRxiv : the preprint server for biology · 2024Article
- Production of recombinant adeno-associated virus 5 using a novel self-attenuating adenovirus production platform.Molecular therapy. Methods & clinical development · 2024Article
- Temporal insights into molecular and cellular responses during rAAV production in HEK293T cells.Molecular therapy. Methods & clinical development · 2024Article
- Enhanced ER protein processing gene expression increases rAAV yield and full capsid ratio in HEK293 cells.Applied microbiology and biotechnology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant adeno-associated virus (rAAV) is a clinically proven viral vector for delivery of therapeutic genes to treat rare diseases. Improving rAAV manufacturing productivity and vector quality is necessary to meet clinical and commercial demand. These goals will require an improved understanding of the cellular response to rAAV production, which is poorly defined. We interrogated the kinetic transcriptional response of HEK293 cells to rAAV production following transient plasmid transfection, under manufacturing-relevant conditions, using RNA-seq. Time-series analyses identified a robust cellular response to transfection and rAAV production, with 1,850 transcripts differentially expressed. Gene Ontology analysis determined upregulated pathways, including inflammatory and antiviral responses, with several interferon-stimulated cytokines and chemokines being upregulated at the protein level. Literature-based pathway prediction implicated multiple pathogen pattern sensors and signal transducers in up-regulation of inflammatory and antiviral responses in response to transfection and rAAV replication. Systematic analysis of the cellular transcriptional response to rAAV production indicates that host cells actively sense vector manufacture as an infectious insult. This dataset may therefore illuminate genes and pathways that influence rAAV production, thereby enabling the rational design of next-generation manufacturing platforms to support safe, effective, and affordable AAV-based gene therapies.
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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.