ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Induction of immune tolerance to FIX following muscular AAV gene transfer is AAV-dose/FIX-level dependent.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Teaching an old vector new tricks: the surprising versatility of AAV vaccines.Journal of virology · 2025Review
- 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
- Lessons learned from lung and liver in-vivo gene therapy: implications for the future.Expert opinion on biological therapy · 2018Review
- Role of antigen-specific regulatory CD4+CD25+ T cells in tolerance induction after neonatal IP administration of AAV-hF.IX.Gene therapy · 2013Article
- Oral vaccination with adeno-associated virus vectors expressing the Neu oncogene inhibits the growth of murine breast cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Muscle-directed anti-Aβ single-chain antibody delivery via AAV1 reduces cerebral Aβ load in an Alzheimer's disease mouse model.Journal of molecular neuroscience : MN · 2013Article
- Liver transplant tolerance and its application to the clinic: can we exploit the high dose effect?Clinical & developmental immunology · 2013Review
- MicroRNA-150-regulated vectors allow lymphocyte-sparing transgene expression in hematopoietic gene therapy.Gene therapy · 2012Article
- Inhibition and promotion of tumor growth with adeno-associated virus carcinoembryonic antigen vaccine and Toll-like receptor agonists.Cancer gene therapy · 2011Article
- Muscle-directed gene therapy for hemophilia B with more efficient and less immunogenic AAV vectors.Journal of thrombosis and haemostasis : JTH · 2011Article
- Safety of AAV factor IX peripheral transvenular gene delivery to muscle in hemophilia B dogs.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Gel-mediated delivery of AAV1 vectors corrects ventilatory function in Pompe mice with established disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Regulatory T cells and immune tolerance to coagulation factor IX in the context of intramuscular AAV1 gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
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4 authors at 1 institution in 1 country.
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Abstract
Direct intramuscular injection (IM) of adeno-associated virus (AAV) has been proven a safe and potentially efficient procedure for gene therapy of many genetic diseases including hemophilia B. It is, however, contentious whether high antigen level induces tolerance or immunity to coagulation factor IX (FIX) following IM of AAV. We recently reported induction of FIX-specific immune tolerance by IM of AAV serotype one (AAV1) vector in mice. We hypothesize that the expression of high levels of FIX is critical to induction of FIX tolerance. In this study, we investigated the correlation among AAV dose, FIX expression, and tolerance induction. We observed that induction of immune tolerance or immunity to FIX was dependent on the dose of AAV1-human FIX (hFIX) given and the level of FIX antigen expressed in both normal and hemophilia mice. We then defined the minimum AAV1-hFIX dose and the lowest level of FIX needed for FIX tolerance. Different from hepatic AAV-hFIX gene transfer, we found that FIX tolerance induced by IM of AAV1 was not driven by regulatory T cells. These results provided further insight into the mechanism(s) of FIX tolerance, contributing to development of hemophilia gene therapy, and optimization of FIX tolerance induction protocols.
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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.