ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Impact of the underlying mutation and the route of vector administration on immune responses to factor IX in gene therapy for hemophilia B.
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 78 papers.
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Who cites it
78 citing papers in PubMed.
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- Assessment of Immune Responses Against AAV Encoded Transgene Products.The AAPS journal · 2026Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene therapy for hemophilia - From basic science to first approvals of "one-and-done" therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Redundancy in Innate Immune Pathways That Promote CD8Viruses · 2024Article
- TLR9-independent CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Polyfunctional T cells and unique cytokine clusters imprint the anti rAAV2/rAAV9 vector immune response.Frontiers in immunology · 2024Article
- Factor IX administration in the skin primes inhibitor formation and sensitizes hemophilia B mice to systemic factor IX administration.Research and practice in thrombosis and haemostasis · 2023Article
- Article
- Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver.Molecular genetics and metabolism reports · 2023Article
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Suppression of anti-drug antibody formation against coagulation factor VIII by oral delivery of anti-CD3 monoclonal antibody in hemophilia A mice.Cellular immunology · 2023Article
- Distinct functions and transcriptional signatures in orally induced regulatory T cell populations.Frontiers in immunology · 2023Article
- Comprehensive Comparison of AAV Purification Methods: Iodixanol Gradient Centrifugation vs. Immuno-Affinity Chromatography.Advances in cell and gene therapy · 2023Article
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
- Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells.Molecular therapy. Methods & clinical development · 2021Article
- CAR- and TRuC-redirected regulatory T cells differ in capacity to control adaptive immunity to FVIII.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.Frontiers in immunology · 2021Review
- T Cell-Mediated Immune Responses to AAV and AAV Vectors.Frontiers in immunology · 2021Review
- Effect of CpG Depletion of Vector Genome on CD8Frontiers in immunology · 2021Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Immune responses to factor IX (F.IX), a major concern in gene therapy for hemophilia, were analyzed for adeno-associated viral (AAV-2) gene transfer to skeletal muscle and liver as a function of the F9 underlying mutation. Vectors identical to those recently used in clinical trials were administered to four lines of hemophilia B mice on a defined genetic background [C3H/HeJ with deletion of endogenous F9 and transgenic for a range of nonfunctional human F.IX (hF.IX) variants]. The strength of the immune response to AAV-encoded F.IX inversely correlated with the degree of conservation of endogenous coding information and levels of endogenous antigen. Null mutation animals developed T- and B-cell responses in both protocols. However, inhibitor titers were considerably higher upon muscle gene transfer (or protein therapy). Transduced muscles of Null mice had strong infiltrates with CD8+ cells, which were much more limited in the liver and not seen for the other mutations. Sustained expression was achieved with liver transduction in mice with crm(-) nonsense and missense mutations, although they still formed antibodies upon muscle gene transfer. Therefore, endogenous expression prevented T-cell responses more effectively than antibody formation, and immune responses varied substantially depending on the protocol and the underlying mutation.
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