ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large genomes in hemophilia mouse and dog models: a strategy for broad clinical application.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 118 citations in OpenAlex.
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- Modulating nuclear stiffness and envelope barrier facilitates AAV nuclear entry and reduces immunogenicity.Nature communications · 2026Article
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Long-Term Liver-Targeted AAV8 Gene Therapy for Mucopolysaccharidosis IVA.Current issues in molecular biology · 2025Article
- Evaluation of AAV vectors with tissue-specific or ubiquitous promoters in a mouse model of mucopolysaccharidosis type IVA.Molecular therapy. Methods & clinical development · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control.Molecular therapy. Nucleic acids · 2025Article
- Structural studies of Parvoviridae capsid assembly and evolution: implications for novel AAV vector design.Frontiers in artificial intelligence · 2025Review
- Immunogenicity risk assessment of empty capsids present in adeno-associated viral vectors using predictive innate immune responses.Journal of pharmaceutical sciences · 2024Article
- The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders.Nature communications · 2024Article
- Enhanced transgene expression from single-stranded AAV vectors in human cellsMolecular therapy. Nucleic acids · 2024Article
- Recent advances in various adeno-associated viruses (AAVs) as gene therapy agents in hepatocellular carcinoma.Virology journal · 2024Review
- MiR133b-mediated inhibition of EGFR-PTK pathway promotes rAAV2 transduction by facilitating intracellular trafficking and augmenting second-strand synthesis.Journal of cellular and molecular medicine · 2023Article
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Review
- Article
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
- Directed evolution of adeno-associated virus for efficient gene delivery to microglia.Nature methods · 2022Article
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
- Chimeric Mice Engrafted With Canine Hepatocytes Exhibits Similar AAV Transduction Efficiency to Hemophilia B Dog.Frontiers in pharmacology · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Delivery of genes that are larger than the wild-type adeno-associated virus (AAV) 4,681 nucleotide genome is inefficient using AAV vectors. We previously demonstrated in vitro that concurrent proteasome inhibitor (PI) treatment improves transduction by AAV vectors encoding oversized transgenes. In this study, an AAV vector with a 5.6 kilobase (kb) factor VIII expression cassette was used to test the effect of an US Food and Drug Administration-approved PI (bortezomib) treatment concurrent with vector delivery in vivo. Intrahepatic vector delivery resulted in factor VIII expression that persisted for >1 year in hemophilia mice. Single-dose bortezomib given with AAV2 or AAV8 factor VIII vector enhanced expression on average ~600 and ~300%, respectively. Moreover, coadministration of AAV8.canineFVIII (1 × 10(13) vg/kg) and bortezomib in hemophilia A dogs (n = 4) resulted in normalization of the whole blood clotting time (WBCT) and 90% reduction in hemorrhages for >32 months compared to untreated hemophilia A dogs (n = 3) or dogs administered vector alone (n = 3). Demonstration of long-term phenotypic correction of hemophilia A dogs with combination adjuvant bortezomib and AAV vector expressing the oversized transgene establishes preclinical studies that support testing in humans and provides a working paradigm to facilitate a significant expansion of therapeutic targets for human gene therapy.
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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.