ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Intrinsic transgene immunogenicity gears CD8(+) T-cell priming after rAAV-mediated muscle gene transfer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- CD8+ T cell activation occurs 24 hours after AAV administration and is driven by muscle promoter specificity.JCI insight · 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
- Interindividual variability in immune response to AAV ocular gene delivery across species impedes immunomonitoring.JCI insight · 2026Article
- Tuning ProteinMPNN to reduce protein visibility via MHC Class I through direct preference optimization.Protein engineering, design & selection : PEDS · 2025Article
- A novel decoding strategy for ProteinMPNN to design with less visibility to cytotoxic T-lymphocytes.Computational and structural biotechnology journal · 2025Article
- Recent Advances in Designing Adeno-Associated Virus-Based Vaccines Against Viral Infections.Pharmaceutics · 2024Review
- Tumor antigen-loaded AAV vaccine drives protective immunity in a melanoma animal model.Molecular therapy. Methods & clinical development · 2023Article
- Immune Responses and Immunosuppressive Strategies for Adeno-Associated Virus-Based Gene Therapy for Treatment of Central Nervous System Disorders: Current Knowledge and Approaches.Human gene therapy · 2022Review
- Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back.Journal of personalized medicine · 2020Review
- Variability in Cardiac miRNA-122 Level Determines Therapeutic Potential of miRNA-Regulated AAV Vectors.Molecular therapy. Methods & clinical development · 2020Article
- An Engineered AAV6-Based Vaccine Induces High Cytolytic Anti-Tumor Activity by Directly Targeting DCs and Improves Ag Presentation.Molecular therapy oncolytics · 2019Article
- Regulatory T cells and TLR9 activation shape antibody formation to a secreted transgene product in AAV muscle gene transfer.Cellular immunology · 2019Article
- Dual muscle-liver transduction imposes immune tolerance for muscle transgene engraftment despite preexisting immunity.JCI insight · 2019Article
- Cross-Presentation of Skin-Targeted Recombinant Adeno-associated Virus 2/1 Transgene Induces Potent Resident Memory CD8Journal of virology · 2019Article
- Intradermal Immunization with rAAV1 Vector Induces Robust Memory CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer.Current gene therapy · 2015Review
Corrections and comments
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Authors and funding
11 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antitransgene CD8(+) T-cell responses are an important hurdle after recombinant adeno-associated virus (rAAV) vector-mediated gene transfer. Indeed, depending on the mutational genotype of the host, transgene amino-acid sequences of foreign origin can elicit deleterious cellular and humoral responses. We compared here two different major histocompatibility complex (MHC) class I epitopes of an engineered ovalbumin transgene delivered in muscle tissue by rAAV1 vector and found very different strength of CD8 responses, muscle destruction being correlated with the course of the immunodominant response. We further demonstrate that robust CD8(+) T-cell priming can occur through the cross-presentation pathway but requires the presence of either a strong MHC class II epitope or antibodies to the transgene product. Finally, manipulating transgene subcellular localization, we found that provided we avoid transgene expression in antigen presenting cells, the poorly accessible cytosolic form of ovalbumin transgene lacking strong MHC II epitope, evades CD8(+) T-cell priming and remains permanently expressed in muscle with no immune cell infiltration. Our results demonstrate that the intrinsic immunogenicity of transgenes delivered with rAAV vector in muscle can be manipulated in a rational manner to avoid adverse immune responses.
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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.