ArticleJournal of translational medicine2014
Role of the vector genome and underlying factor IX mutation in immune responses to AAV gene therapy for hemophilia B.
Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- Redundancy in Innate Immune Pathways That Promote CD8Viruses · 2024Article
- TLR9-independent CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.Nature medicine · 2023Article
- Hierarchically tumor-activated nanoCRISPR-Cas13a facilitates efficient microRNA disruption for multi-pathway-mediated tumor suppression.Theranostics · 2023Article
- Coagulation factor IX gene transfer to non-human primates using engineered AAV3 capsid and hepatic optimized expression cassette.Molecular therapy. Methods & clinical development · 2021Article
- AAV8 locoregional delivery induces long-term expression of an immunogenic transgene in macaques despite persisting local inflammation.Molecular therapy. Methods & clinical development · 2021Article
- Effect of CpG Depletion of Vector Genome on CD8Frontiers in immunology · 2021Article
- Exploiting Single-Cell Tools in Gene and Cell Therapy.Frontiers in immunology · 2021Review
- Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020Review
- Type I IFN Sensing by cDCs and CD4Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Immune Responses to Viral Gene Therapy Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- TLR9 signaling mediates adaptive immunity following systemic AAV gene therapy.Cellular immunology · 2019Article
- Regulatory T cells and TLR9 activation shape antibody formation to a secreted transgene product in AAV muscle gene transfer.Cellular immunology · 2019Article
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- TLR9-Activating CpG-B ODN but Not TLR7 Agonists Triggers Antibody Formation to Factor IX in Muscle Gene Transfer.Human gene therapy methods · 2019Article
- Viral vectors for therapy of neurologic diseases.Neuropharmacology · 2017Review
- Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8Blood · 2017Article
- Alternative Start Sites Downstream of Non-Sense Mutations Drive Antigen Presentation and Tolerance Induction to C-Terminal Epitopes.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSelf-complementary adeno-associated virus (scAAV) vectors have become a desirable vector for therapeutic gene transfer due to their ability to produce greater levels of transgene than single-stranded AAV (ssAAV). However, recent reports have suggested that scAAV vectors are more immunogenic than ssAAV. In this study, we investigated the effects of a self-complementary genome during gene therapy with a therapeutic protein, human factor IX (hF.IX).
methodsHemophilia B mice were injected intramuscularly with ss or scAAV1 vectors expressing hF.IX. The outcome of gene transfer was assessed, including transgene expression as well as antibody and CD8⁺ T cell responses to hF.IX.
resultsSelf-complementary AAV1 vectors induced similar antibody responses (which eliminated systemic hF.IX expression) but stronger CD8⁺ T cell responses to hF.IX relative to ssAAV1 in mice with F9 gene deletion. As a result, hF.IX-expressing muscle fibers were effectively eliminated in scAAV-treated mice. In contrast, mice with F9 nonsense mutation (late stop codon) lacked antibody or T cell responses, thus showing long-term expression regardless of the vector genome.
conclusionsThe nature of the AAV genome can impact the CD8⁺ T cell response to the therapeutic transgene product. In mice with endogenous hF.IX expression, however, this enhanced immunogenicity did not break tolerance to hF.IX, suggesting that the underlying mutation is a more important risk factor for transgene-specific immunity than the molecular form of the AAV genome.
Indexed as
Identifiers
What OpenQuestion holds
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.