ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Safety of AAV factor IX peripheral transvenular gene delivery to muscle in hemophilia B dogs.
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 45 papers.
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Who cites it
45 citing papers in PubMed, 63 citations in OpenAlex.
- Immune responses to intramuscular administration of alipogene tiparvovec (AAV1-LPL(S447X)) in a phase II clinical trial of lipoprotein lipase deficiency gene therapy.Human gene therapy · 2014Trial
- Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy.Science translational medicine · 2023Article
- AAV8 locoregional delivery induces long-term expression of an immunogenic transgene in macaques despite persisting local inflammation.Molecular therapy. Methods & clinical development · 2021Article
- Evolutionary insights into coagulation factor IX Padua and other high-specific-activity variants.Blood advances · 2021Article
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Review
- Towards the clinical translation of optogenetic skeletal muscle stimulation.Pflugers Archiv : European journal of physiology · 2020Review
- Muscle-Directed Delivery of an AAV1 Vector Leads to Capsid-Specific T Cell Exhaustion in Nonhuman Primates and Humans.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Gene Therapy for Hemophilia: Facts and Quandaries in the 21st Century.Mediterranean journal of hematology and infectious diseases · 2020Review
- Role of Regulatory T Cell and Effector T Cell Exhaustion in Liver-Mediated Transgene Tolerance in Muscle.Molecular therapy. Methods & clinical development · 2019Article
- Superior human hepatocyte transduction with adeno-associated virus vector serotype 7.Gene therapy · 2019Article
- Five Years of Successful Inducible Transgene Expression Following Locoregional Adeno-Associated Virus Delivery in Nonhuman Primates with No Detectable Immunity.Human gene therapy · 2019Article
- Bridging from Intramuscular to Limb Perfusion Delivery of rAAV: Optimization in a Non-human Primate Study.Molecular therapy. Methods & clinical development · 2019Article
- FGF21 gene therapy as treatment for obesity and insulin resistance.EMBO molecular medicine · 2018Article
- Complete correction of hemophilia B phenotype by FIX-Padua skeletal muscle gene therapy in an inhibitor-prone dog model.Blood advances · 2018Article
- Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial.Human gene therapy · 2017Review
- Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy.Nature communications · 2017Article
- And Then There Was Light: Perspectives of Optogenetics for Deep Brain Stimulation and Neuromodulation.Frontiers in neuroscience · 2017Review
- Recombinant AAV Integration Is Not Associated With Hepatic Genotoxicity in Nonhuman Primates and Patients.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Delivery of Adeno-Associated Virus Gene Therapy by Intravascular Limb Infusion Methods.Human gene therapy. Clinical development · 2015Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Muscle represents an attractive target tissue for adeno-associated virus (AAV) vector-mediated gene transfer for hemophilia B (HB). Experience with direct intramuscular (i.m.) administration of AAV vectors in humans showed that the approach is safe but fails to achieve therapeutic efficacy. Here, we present a careful evaluation of the safety profile (vector, transgene, and administration procedure) of peripheral transvenular administration of AAV-canine factor IX (cFIX) vectors to the muscle of HB dogs. Vector administration resulted in sustained therapeutic levels of cFIX expression. Although all animals developed a robust antibody response to the AAV capsid, no T-cell responses to the capsid antigen were detected by interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISpot). Interleukin (IL)-10 ELISpot screening of lymphocytes showed reactivity to cFIX-derived peptides, and restimulation of T cells in vitro in the presence of the identified cFIX epitopes resulted in the expansion of CD4(+)FoxP3(+)IL-10(+) T-cells. Vector administration was not associated with systemic inflammation, and vector spread to nontarget tissues was minimal. At the local level, limited levels of cell infiltrates were detected when the vector was administered intravascularly. In summary, this study in a large animal model of HB demonstrates that therapeutic levels of gene transfer can be safely achieved using a novel route of intravascular gene transfer to muscle.
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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.