ReviewFrontiers in immunology2020
The Immune Response to the fVIII Gene Therapy in Preclinical Models.
Review in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 26 citations in OpenAlex.
- Nanoparticles targeting liver sinusoidal endothelial cells improve tolerance to vector and transgene antigens through tolerance spreading.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Safety of Adeno-Associated Viral Vectors in Gene Therapy: Mechanisms of Toxicity, Clinical Risks, and Strategies for Their Minimization.International journal of molecular sciences · 2026Review
- Immune Response Associated Hepatotoxicity in Hemophilia Gene Therapy: Mechanisms, Management, and Challenges.Journal of hematology · 2026Review
- Treatment of canine hemophilia A via intraosseous delivery of a platelet-specific factor VIII-lentiviral vector.Blood vessels, thrombosis & hemostasis · 2026Article
- The Epigenetic Landscape of Hemophilia.Current molecular medicine · 2026Review
- Nine areas with outstanding challenges for hemophilia B research.Therapeutic advances in hematology · 2026Review
- Knowledge mapping and bibliometric insights into gene therapy for rare inherited hematologic pathologies: focus on sickle cell disease, hemophilia, and thalassemia.Orphanet journal of rare diseases · 2025Article
- How Close Are We to Achieving Durable and Efficacious Gene Therapy for Hemophilia A and B?Genes · 2025Review
- Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy.International journal of molecular sciences · 2025Review
- The role of FoxO3a in the pathogenesis of osteoarthritis and its therapeutic applications.Frontiers in immunology · 2025Review
- Blunting specific T-dependent antibody responses with engineered "decoy" B cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Humanization and functional characterization of enhanced coagulation factor IX variants identified through ancestral sequence reconstruction.Journal of thrombosis and haemostasis : JTH · 2024Article
- Mesenchymal Stem Cell-Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?Journal of inflammation research · 2024Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice.Blood advances · 2022Article
- Nonhuman Primates in Translational Research.Annual review of animal biosciences · 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
- Article
- Non-genotoxic conditioning facilitates hematopoietic stem cell gene therapy for hemophilia A using bioengineered factor VIII.Molecular therapy. Methods & clinical development · 2021Article
- Gene Therapy for Inherited Bleeding Disorders.Seminars in thrombosis and hemostasis · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Neutralizing antibodies to factor VIII (fVIII), referred to as "inhibitors," remain the most challenging complication post-fVIII replacement therapy. Preclinical development of novel fVIII products involves studies incorporating hemophilia A (HA) and wild-type animal models. Though immunogenicity is a critical aspect of preclinical pharmacology studies, gene therapy studies tend to focus on fVIII expression levels without major consideration for immunogenicity. Therefore, little clarity exists on whether preclinical testing can be predictive of clinical immunogenicity risk. Despite this, but perhaps due to the potential for transformative benefits, clinical gene therapy trials have progressed rapidly. In more than two decades, no inhibitors have been observed. However, all trials are conducted in previously treated patients without a history of inhibitors. The current review thus focuses on our understanding of preclinical immunogenicity for HA gene therapy candidates and the potential indication for inhibitor treatment, with a focus on product- and platform-specific determinants, including fVIII transgene sequence composition and tissue/vector biodistribution. Currently, the two leading clinical gene therapy vectors are adeno-associated viral (AAV) and lentiviral (LV) vectors. For HA applications, AAV vectors are liver-tropic and employ synthetic, high-expressing, liver-specific promoters. Factors including vector serotype and biodistribution, transcriptional regulatory elements, transgene sequence, dosing, liver immunoprivilege, and host immune status may contribute to tipping the scale between immunogenicity and tolerance. Many of these factors can also be important in delivery of LV-fVIII gene therapy, especially when delivered intravenously for liver-directed fVIII expression. However,
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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.