ArticleHuman gene therapy methods2014
Efficient production of dual recombinant adeno-associated viral vectors for factor VIII delivery.
Article in Human gene therapy methods, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Inhibition of ACSL4 Alleviates Parkinsonism Phenotypes by Reduction of Lipid Reactive Oxygen Species.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Adding recombinant AAVs to the cancer therapeutics mix.Molecular therapy oncolytics · 2022Review
- Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human heavy chain and the rat light chain.Frontiers of medicine · 2022Article
- Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion.Signal transduction and targeted therapy · 2022Article
- Genomic Designs of rAAVs Contribute to Pathological Changes in the Livers and Spleens of Mice.Advances in cell and gene therapy · 2022Article
- Detailed Protocol for the Novel and Scalable Viral Vector Upstream Process for AAV Gene Therapy Manufacturing.Human gene therapy · 2021Article
- Identification of Key Coagulation Activity Determining Elements in Canine Factor VIII.Molecular therapy. Methods & clinical development · 2020Article
- Rapid AAV-Neutralizing Antibody Determination with a Cell-Binding Assay.Molecular therapy. Methods & clinical development · 2019Article
- Codon-Optimization of Wild-Type Adeno-Associated Virus Capsid Sequences Enhances DNA Family Shuffling while Conserving Functionality.Molecular therapy. Methods & clinical development · 2019Article
- Transduction of Adeno-Associated Virus Vectors Targeting Hair Cells and Supporting Cells in the Neonatal Mouse Cochlea.Frontiers in cellular neuroscience · 2019Article
- Evaluation of the activity levels of rat FVIII and human FVIII delivered by adeno-associated viral vectors both in vitro and in vivo.Blood cells, molecules & diseases · 2018Article
- A Robust System for Production of Superabundant VP1 Recombinant AAV Vectors.Molecular therapy. Methods & clinical development · 2017Article
- Emerging Gene Therapies for Genetic Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2017Review
- The hepatocyte-specific HNF4α/miR-122 pathway contributes to iron overload-mediated hepatic inflammation.Blood · 2017Article
- Syngeneic AAV Pseudo-particles Potentiate Gene Transduction of AAV Vectors.Molecular therapy. Methods & clinical development · 2017Article
- High-Density Recombinant Adeno-Associated Viral Particles are Competent Vectors for In Vivo Transduction.Human gene therapy · 2016Article
- High-Efficiency Transduction of Primary Human Hematopoietic Stem/Progenitor Cells by AAV6 Vectors: Strategies for Overcoming Donor-Variation and Implications in Genome Editing.Scientific reports · 2016Article
- Development of Optimized AAV Serotype Vectors for High-Efficiency Transduction at Further Reduced Doses.Human gene therapy methods · 2016Article
- Evaluation of the biological differences of canine and human factor VIII in gene delivery: implications in human hemophilia treatment.Gene therapy · 2016Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Recombinant adeno-associated viral (rAAV) vectors have gained attention for human gene therapy because of their high safety and clinical efficacy profile. For factor VIII gene delivery, splitting the coding region between two AAV vectors remains a viable strategy to avoid the packaging capacity limitation (∼5.0 kb). However, it is time-consuming and labor-intensive to produce two rAAV vectors in separate batches. Here we demonstrated successful production of dual rAAV vectors for hemophilia A gene therapy in a single preparation. When the AAV vector plasmids carrying the human factor VIII heavy chain (hHC) and the light chain (hLC) expression cassettes were cotransfected into 293 cells along with the AAV rep&cap and mini-adenovirus helper plasmids, both rAAV-hHC and rAAV-hLC were produced at the desired ratio and in high titer. Interestingly, the rAAV-hHC vectors always yielded higher titers than rAAV-hLC vectors as a result of more efficient replication of rAAV-hHC genomes. The resulting vectors were effective in transducing the tissue culture cells in vitro. When these vectors were administered to hemophilia A mice, factor VIII was detected in the mouse plasma by both the activated partial thromboplastin time assay and enzyme-linked immunosorbent assay. The functional activity as well as the antigen levels of secreted factor VIII were similar to those of vectors produced by the traditional method. The dual-vector production method has been successfully extended to both AAV2 and AAV8 serotypes. In conclusion, cotransfection of vector plasmids presents an efficient method for producing dual or multiple AAV vectors at significantly reduced cost and labor.
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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.