ArticleJCI insight2019
Circumventing cellular immunity by miR142-mediated regulation sufficiently supports rAAV-delivered OVA expression without activating humoral immunity.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 47 citations in OpenAlex.
- Lipid nanoparticles enable mRNA delivery to diverse cell types of the inner Retina.Molecular therapy. Nucleic acids · 2026Article
- Advances in vehicles for in situ delivery: From classical vectors to biologically inspired structures.Synthetic and systems biotechnology · 2026Review
- Long-term depletion of KIR3DL01+ NK cells by adeno-associated viral-vectored antibody delivery alters chronic SIV infection.PLoS pathogens · 2026Article
- CD8+ T cell activation occurs 24 hours after AAV administration and is driven by muscle promoter specificity.JCI insight · 2026Article
- Encapsulin-Protected Immunotherapeutic Complexes: Bacteria-Derived Nanoparticles for mRNA Delivery to Eukaryotic Cells.ChemMedChem · 2026Article
- Overcoming host immune responses to an AAV-delivered HIV-1 bNAb in rhesus macaques mediated by co-delivery of PD-L1.bioRxiv : the preprint server for biology · 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
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- Smac mimetic combined with eCD4-Ig reverses latency without reducing SHIV reservoirs in rhesus macaques.The Journal of clinical investigation · 2026Article
- Combining Anti-Inflammatory Drugs and Cell-Specific Expression-Suppression Reduces the Adjuvant Activity of mRNA-LNPs.Molecular pharmaceutics · 2026Article
- Deep learning-guided design of cell type-specific AAV promoters.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
- Base and Prime Editing for Inherited Retinal Diseases: Delivery Platforms, Safety, Efficacy, and Translational Perspectives.Pharmaceutics · 2025Review
- Article
- Absolute quantification of mammalian microRNAs for therapeutic RNA cleavage and detargeting.RNA (New York, N.Y.) · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The ambition for a one-and-done vision-saving AAV vector.Molecular therapy. Methods & clinical development · 2025Article
- AAV-based gene delivery of antimicrobial peptides to combat drug-resistant pathogens.Applied and environmental microbiology · 2025Review
- Effective Reduction of Transgene-Specific Immune Response With rAAV Vectors Co-Expressing miRNA-UL112-5p or ERAP1 shRNA.Journal of cellular and molecular medicine · 2025Article
- The Intra-Articular Delivery of a Low-Dose Adeno-Associated Virus-IL-1 Receptor Antagonist Vector Alleviates the Progress of Arthritis in an Osteoarthritis Rat Model.Pharmaceutics · 2024Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
Abstract
Recombinant adeno-associated virus (rAAV)-mediated gene delivery can efficiently target muscle tissues to serve as "biofactories" for secreted proteins in prophylactic and therapeutic scenarios. Nevertheless, efficient rAAV-mediated gene delivery is often limited by host immune responses against the transgene product. The development of strategies to prevent anti-transgene immunity is therefore crucial. The employment of endogenous microRNA (miRNA)-mediated regulation to detarget transgene expression from antigen presenting cells (APCs) has shown promise for reducing immunogenicity. However, the mechanisms underlying miRNA-mediated modulation of anti-transgene immunity by APC detargeting are not fully understood. Using the highly immunogenic ovalbumin (OVA) protein as a proxy for foreign antigens, we show that rAAV vectors containing miR142 binding sites efficiently repress co-stimulatory signals in dendritic cells, significantly blunt the cytotoxic T cell response, allow for sustained transgene expression in skeletal myoblasts, and attenuate clearance of transduced muscle cells in mice. Furthermore, the blunting of humoral immunity against circulating OVA correlates with detargeting of OVA expression from APCs. This demonstrates that incorporating APC-specific miRNA binding sites into rAAV vectors provides an effective strategy for reducing transgene-specific immune response. This approach holds promise for clinical applications where the safe and efficient delivery of a prophylactic or therapeutic protein is desired.
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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.