ArticleHuman gene therapy2008
Complete correction of hemophilia A with adeno-associated viral vectors containing a full-size expression cassette.
Article in Human gene therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Quantitative analysis of genome truncation patterns in oversized adeno-associated virus vectors.Biotechnology letters · 2026Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Evaluation of a rapid multi-attribute combinatorial high-throughput UV-Vis/DLS/SLS analytical platform for rAAV quantification and characterization.Molecular therapy. Methods & clinical development · 2024Article
- Adding recombinant AAVs to the cancer therapeutics mix.Molecular therapy oncolytics · 2022Review
- Molecular analysis of AAV5-hFVIII-SQ vector-genome-processing kinetics in transduced mouse and nonhuman primate livers.Molecular therapy. Methods & clinical development · 2022Article
- Genomic Designs of rAAVs Contribute to Pathological Changes in the Livers and Spleens of Mice.Advances in cell and gene therapy · 2022Article
- Minimal Essential Human Factor VIII Alterations Enhance Secretion and Gene Therapy Efficiency.Molecular therapy. Methods & clinical development · 2020Article
- Bioengineering hemophilia A-specific microvascular grafts for delivery of full-length factor VIII into the bloodstream.Blood advances · 2019Article
- Target-Cell-Directed Bioengineering Approaches for Gene Therapy of Hemophilia A.Molecular therapy. Methods & clinical development · 2018Article
- Characteristics of Minimally Oversized Adeno-Associated Virus Vectors Encoding Human Factor VIII Generated Using Producer Cell Lines and Triple Transfection.Human gene therapy methods · 2017Article
- Evaluation of the biological differences of canine and human factor VIII in gene delivery: implications in human hemophilia treatment.Gene therapy · 2016Article
- The impact of minimally oversized adeno-associated viral vectors encoding human factor VIII on vector potency in vivo.Molecular therapy. Methods & clinical development · 2016Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- Efficient production of dual recombinant adeno-associated viral vectors for factor VIII delivery.Human gene therapy methods · 2014Article
- Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery.Molecular therapy. Methods & clinical development · 2014Article
- Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A.PloS one · 2014Article
- Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.Gene therapy · 2013Article
- Article
- Myosin7a deficiency results in reduced retinal activity which is improved by gene therapy.PloS one · 2013Article
- Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia.Gene therapy · 2012Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Hemophilia A is caused by a deficiency in the factor VIII (FVIII) gene. Constrained by limited packaging capacity, even the 4.3-kb B domain-deleted FVIII remained a challenge for delivery by a single adeno-associated viral (AAV) vector. Studies have shown that up to a 6.6-kb vector sequence may be packaged into AAV virions, which suggested an alternative strategy for hemophilia A gene therapy. To explore the usefulness of AAV vectors carrying an oversized FVIII gene, we constructed the AAV-FVIII vector under the control of a beta-actin promoter with a cytomegalovirus enhancer (CB) and a bovine growth hormone (bGH) poly(A) sequence. The CB promoter plus bGH signal was shown to be 3- to 5-fold more potent than the mini-transthyretin (TTR) promoter with a synthetic poly(A) sequence for directing FVIII expression in the liver. Despite the 5.75-kb genome size of pAAV-CB-FVIII, sufficient AAV vectors were produced for in vivo testing. Approximately 3- to 5-fold more FVIII secretion was observed in animals receiving AAV-CB-FVIII vectors than in those receiving standard-sized AAV-TTR-FVIII vectors. Both the activated partial thromboplastin time assay and the whole blood thromboelastographic analysis confirmed that AAV-FVIII vectors fully corrected the bleeding phenotype of hemophilia mice. These results suggest that AAV vectors with an oversized genome should be useful for not only hemophilia A gene therapy but also other diseases with large cDNA such as muscular dystrophy and cystic fibrosis.
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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.