ArticleThe Journal of clinical investigation2009
Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 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
117 citing papers in PubMed, 188 citations in OpenAlex.
- Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Trial
- Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial.JAMA ophthalmology · 2014Trial
- Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression.The Journal of clinical investigation · 2013Trial
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- Combined Plasmid Redesign and Transfection Optimization Significantly Increases Upstream AAV Titers While Maintaining Vector Quality and In Vivo Potency.Microorganisms · 2026Article
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Current Status of Clinical Gene Therapy for Hemophilia and Globin Disorders.Journal of blood medicine · 2026Review
- Reduced rAAV interference enhances rcAAV detection sensitivity.Molecular therapy. Methods & clinical development · 2025Article
- Can Sex-based Variations in the Immune Responses to AAV Gene Therapy Affect Safety and Efficacy? A Review of Current Understanding.The AAPS journal · 2025Review
- Recent developments in translational imaging of in vivo gene therapy outcomes.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
- Epitope mapping using immunopeptidomics reveals novel immunodominant CD8 T cell epitopes of the AAV9 capsid.Frontiers in immunology · 2025Article
- Viral vectors in neurodegenerative diseases: immune responses and therapeutic applications.Frontiers in neurology · 2025Review
- Sonogenetics in the Treatment of Chronic Diseases: A New Method for Cell Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Review
- Recent Advances in Designing Adeno-Associated Virus-Based Vaccines Against Viral Infections.Pharmaceutics · 2024Review
- Multicenter assessment and longitudinal study of the prevalence of antibodies and related adaptive immune responses to AAV in adult males with hemophilia.Gene therapy · 2024Article
- Review
- Thrombotic microangiopathy following systemic AAV administration is dependent on anti-capsid antibodies.The Journal of clinical investigation · 2024Article
57 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
12 authors at 2 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) vectors are effective gene delivery vehicles mediating long-lasting transgene expression. Data from a clinical trial of AAV2-mediated hepatic transfer of the Factor IX gene (F9) into hemophilia B subjects suggests that CTL responses against AAV capsid can eliminate transduced hepatocytes and prevent long-term F9 expression. However, the capacity of hepatocytes to present AAV capsid-derived antigens has not been formally demonstrated, nor whether transduction by AAV sensitizes hepatocytes for CTL-mediated destruction. To investigate the fate of capsids after transduction, we engineered a soluble TCR for the detection of capsid-derived peptide:MHC I (pMHC) complexes. TCR multimers exhibited antigen and HLA specificity and possessed high binding affinity for cognate pMHC complexes. With this reagent, capsid pMHC complexes were detectable by confocal microscopy following AAV-mediated transduction of human hepatocytes. Although antigen presentation was modest, it was sufficient to flag transduced cells for CTL-mediated lysis in an in vitro killing assay. Destruction of hepatocytes was inhibited by soluble TCR, demonstrating a possible application for this reagent in blocking undesirable CTL responses. Together, these studies provide a mechanism for the loss of transgene expression and transient elevations in aminotransferases following AAV-mediated hepatic gene transfer in humans and a potential therapeutic intervention to abrogate these limitations imposed by the host T cell response.
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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.