ArticleMolecular therapy. Methods & clinical development2016
A scalable method for the production of high-titer and high-quality adeno-associated type 9 vectors using the HSV platform.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- What's new and what's next for gene therapy in Pompe disease?Expert opinion on biological therapy · 2022Pooled it
- Enhanced AAV production via rational design of a novel pHelper vector integrated with HSV-1 helper genes.Synthetic and systems biotechnology · 2026Article
- Mammalian synthetic gene circuits for biopharmaceutical development & manufacture.NPJ systems biology and applications · 2025Review
- In vivo applications and toxicities of AAV-based gene therapies in rare diseases.Orphanet journal of rare diseases · 2025Review
- Characterization of factors that influence rAAV yield and quality when produced using rHSV co-infection.Molecular therapy. Methods & clinical development · 2025Article
- Model-Based Characterization of the Metabolism of Recombinant Adeno-Associated Virus (rAAV) Production via Human Embryonic Kidney (HEK293) Cells.Bioengineering (Basel, Switzerland) · 2025Article
- Consecutive Affinity and Ion-Exchange Chromatography for AAV9 Vectors Purification.Biomedicines · 2025Article
- Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47.EMBO molecular medicine · 2024Article
- Development of Stable Packaging and Producer Cell Lines for the Production of AAV Vectors.Microorganisms · 2024Review
- Article
- Mechanistic modeling explains the production dynamics of recombinant adeno-associated virus with the baculovirus expression vector system.Molecular therapy. Methods & clinical development · 2023Article
- AAV genome modification for efficient AAV production.Heliyon · 2023Review
- Multiplexing AAV Serotype-Specific Neutralizing Antibodies in Preclinical Animal Models and Humans.Biomedicines · 2023Article
- rAAV Manufacturing: The Challenges of Soft Sensing during Upstream Processing.Bioengineering (Basel, Switzerland) · 2023Review
- 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
- AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System.Frontiers in neurology · 2022Review
- Detailed Protocol for the Novel and Scalable Viral Vector Upstream Process for AAV Gene Therapy Manufacturing.Human gene therapy · 2021Article
- Mechanistic model for production of recombinant adeno-associated virus via triple transfection of HEK293 cells.Molecular therapy. Methods & clinical development · 2021Article
- NaCl and KCl mediate log increase in AAV vector particles and infectious titers in a specific/timely manner with the HSV platform.Molecular therapy. Methods & clinical development · 2021Article
- Micro-dystrophin AAV Vectors Made by Transient Transfection and Herpesvirus System Are Equally Potent in Treating mdx Mouse Muscle Disease.Molecular therapy. Methods & clinical development · 2020Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Recombinant adeno-associated vectors based on serotype 9 (rAAV9) have demonstrated highly effective gene transfer in multiple animal models of muscular dystrophies and other neurological indications. Current limitations in vector production and purification have hampered widespread implementation of clinical candidate vectors, particularly when systemic administration is considered. In this study, we describe a complete herpes simplex virus (HSV)-based production and purification process capable of generating greater than 1 × 10(14) rAAV9 vector genomes per 10-layer CellSTACK of HEK 293 producer cells, or greater than 1 × 10(5) vector genome per cell, in a final, fully purified product. This represents a 5- to 10-fold increase over transfection-based methods. In addition, rAAV vectors produced by this method demonstrated improved biological characteristics when compared to transfection-based production, including increased infectivity as shown by higher transducing unit-to-vector genome ratios and decreased total capsid protein amounts, shown by lower empty-to-full ratios. Together, this data establishes a significant improvement in both rAAV9 yields and vector quality. Further, the method can be readily adapted to large-scale good laboratory practice (GLP) and good manufacturing practice (GMP) production of rAAV9 vectors to enable preclinical and clinical studies and provide a platform to build on toward late-phases and commercial production.
Identifiers
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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.