ArticleGene therapy2009
An efficient rHSV-based complementation system for the production of multiple rAAV vector serotypes.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 55 citations in OpenAlex.
- Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results.Human gene therapy · 2011Trial
- Characterization of factors that influence rAAV yield and quality when produced using rHSV co-infection.Molecular therapy. Methods & clinical development · 2025Article
- Development of Stable Packaging and Producer Cell Lines for the Production of AAV Vectors.Microorganisms · 2024Review
- Engineered CHO cells as a novel AAV production platform for gene therapy delivery.Scientific reports · 2023Article
- rAAV Manufacturing: The Challenges of Soft Sensing during Upstream Processing.Bioengineering (Basel, Switzerland) · 2023Review
- Synthetic Biology Design as a Paradigm Shift toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies.ACS synthetic biology · 2023Review
- Detailed Protocol for the Novel and Scalable Viral Vector Upstream Process for AAV Gene Therapy Manufacturing.Human gene therapy · 2021Article
- Toxicity and Efficacy Evaluation of an Adeno-Associated Virus Vector Expressing Codon-OptimizedHuman gene therapy · 2020Article
- Bridging from Intramuscular to Limb Perfusion Delivery of rAAV: Optimization in a Non-human Primate Study.Molecular therapy. Methods & clinical development · 2019Article
- Pharmacology of Recombinant Adeno-associated Virus Production.Molecular therapy. Methods & clinical development · 2018Review
- A Robust System for Production of Superabundant VP1 Recombinant AAV Vectors.Molecular therapy. Methods & clinical development · 2017Article
- Production of Recombinant Adeno-associated Virus Vectors Using Suspension HEK293 Cells and Continuous Harvest of Vector From the Culture Media for GMP FIX and FLT1 Clinical Vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- A scalable method for the production of high-titer and high-quality adeno-associated type 9 vectors using the HSV platform.Molecular therapy. Methods & clinical development · 2016Article
- Manufacturing of recombinant adeno-associated viral vectors for clinical trials.Molecular therapy. Methods & clinical development · 2016Review
- Cone-Specific Promoters for Gene Therapy of Achromatopsia and Other Retinal Diseases.Human gene therapy · 2016Article
- Progress with Recombinant Adeno-Associated Virus Vectors for Gene Therapy of Alpha-1 Antitrypsin Deficiency.Human gene therapy methods · 2015Review
- OneBac: platform for scalable and high-titer production of adeno-associated virus serotype 1-12 vectors for gene therapy.Human gene therapy · 2014Article
- Human bocavirus 1 infects commercially available primary human airway epithelium cultures productively.Journal of virological methods · 2014Article
- Aurintricarboxylic acid increases yield of HSV-1 vectors.Molecular therapy. Methods & clinical development · 2014Article
- A versatile adeno-associated virus vector producer cell line method for scalable vector production of different serotypes.Human gene therapy · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant herpes simplex virus type 1 (rHSV)-assisted recombinant adeno-associated virus (rAAV) vector production provides a highly efficient and scalable method for manufacture of clinical grade rAAV vectors. Here, we present an rHSV co-infection system for rAAV production, which uses two ICP27-deficient rHSV constructs, one bearing the rep2 and cap (1, 2 or 9) genes of rAAV, and the second bearing an AAV2 ITR-gene of interest (GOI) cassette. The optimum rAAV production parameters were defined by producing rAAV2/GFP in HEK293 cells, yielding greater than 9000 infectious particles per cell with a 14:1 DNase resistance particle to infectious particle (DRP/ip) ratio. The optimized co-infection parameters were then used to generate large-scale stocks of rAAV1/AAT, which encode the human alpha-1-antitrypsin (hAAT) protein, and purified by column chromatography. The purified vector was extensively characterized by rAAV- and rHSV-specific assays and compared to transfection-made vector for in vivo efficacy in mice through intramuscular injection. The co-infection method was also used to produce rAAV9/AAT for comparison to rAAV1/AAT in vivo. Intramuscular administration of 1 x 10(11) DRP per animal of rHSV-produced rAAV1/AAT and rAAV9/AAT resulted in hAAT protein expression of 5.4 x 10(4) and 9.4 x 10(5) ng ml(-1) serum respectively, the latter being clinically relevant.
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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.