ArticleHuman gene therapy2011
Reproducible high yields of recombinant adeno-associated virus produced using invertebrate cells in 0.02- to 200-liter cultures.
Article in Human gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 92 citations in OpenAlex.
- Advances in viral vector-based delivery systems for gene therapy: a comprehensive review.3 Biotech · 2025Review
- Scalable Production of Recombinant Adeno-Associated Virus Vectors Expressing Soluble Viral Receptors for Broad-Spectrum Inhibition of Porcine Reproductive and Respiratory Syndrome Virus Type 2.Veterinary sciences · 2025Article
- Membrane Filtration of Nanoscale Biomaterials: Model System and Membrane Performance Evaluation for AAV2 Viral Vector Clarification and Recovery.Nanomaterials (Basel, Switzerland) · 2025Article
- Pilot-scale process development for recombinant adeno-associated virus (rAAV) production based on high-density Sf9 cell culture.Virology journal · 2024Article
- Diverting organic waste from landfills via insect biomanufacturing using engineered black soldier flies (Hermetia illucens).Communications biology · 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
- Mechanistic modeling explains the production dynamics of recombinant adeno-associated virus with the baculovirus expression vector system.Molecular therapy. Methods & clinical development · 2023Article
- High-Level rAAV Vector Production by rAdV-Mediated Amplification of Small Amounts of Input Vector.Viruses · 2022Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Current Advances in Adeno-Associated Virus-Mediated Gene Therapy to Prevent Acquired Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2022Review
- Cryo-electron Microscopy of Adeno-associated Virus.Chemical reviews · 2022Review
- Human and Insect Cell-Produced Recombinant Adeno-Associated Viruses Show Differences in Genome Heterogeneity.Human gene therapy · 2022Article
- Comparison of highly pure rAAV9 vector stocks produced in suspension by PEI transfection or HSV infection reveals striking quantitative and qualitative differences.Molecular therapy. Methods & clinical development · 2022Article
- Development and Optimization of a Hydrophobic Interaction Chromatography-Based Method of AAV Harvest, Capture, and Recovery.Molecular therapy. Methods & clinical development · 2020Article
- A Simple, Two-Step, Small-Scale Purification of Recombinant Adeno-Associated Viruses.Journal of virological methods · 2020Article
- Article
- Development of Versatile and Flexible Sf9 Packaging Cell Line-Dependent OneBac System for Large-Scale Recombinant Adeno-Associated Virus Production.Human gene therapy methods · 2019Article
- The Coming Age of Insect Cells for Manufacturing and Development of Protein Therapeutics.Industrial & engineering chemistry research · 2018Article
- Pharmacology of Recombinant Adeno-associated Virus Production.Molecular therapy. Methods & clinical development · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The large amounts of recombinant adeno-associated virus (rAAV) vector needed for clinical trials and eventual commercialization require robust, economical, reproducible, and scalable production processes compatible with current good manufacturing practice. rAAV produced using baculovirus and insect cells satisfies these conditions; however, recovering rAAV particles from 200-liter bioreactors is more complicated than bench-scale vector preparations. Using a variety of processing media, we developed a reliable and routine downstream procedure for rAAV production that is scalable from 0.02- to 200-liter cultures. To facilitate the upstream process, we adapted the titerless infected-cell preservation and scale-up process for rAAV production. Single-use aliquots of cryopreserved baculovirus-infected insect cells (BIIC) are thawed and added to the suspension culture to achieve the desired ratio of BIIC to rAAV-producer cells. By using conditions established with small-scale cultures, rAAV was produced in larger volume cultures. Strikingly consistent rAAV yields were attained in cultures ranging from 10 liters to 200 liters. Based on the final yield, each cell produced 18,000 ± 6,800 particles of purified rAAV in 10-, 20-, 100-, and 200-liter cultures. Thus, with an average cell density of 4.32 × 10(6) cells/ml, ≥ 10(16) purified rAAV particles are produced from 100 to 200 liters. The downstream process resulted in about 20% recovery estimated from comparing the quantities of capsid protein antigen in the crude bioreactor material and in the final, purified product. The ease and reproducibility of rAAV production in 200-liter bioreactors suggest that the limit has not been reached, and 500-liter productions are planned.
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What OpenQuestion holds
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.