ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
High-dose systemic adeno-associated virus vector administration causes liver and sinusoidal endothelial cell injury.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
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- Vectored Immunoprophylaxis for Mucosal Immunity: Advances and Challenges Associated with Recombinant Secretory IgA Expression.Vaccines · 2026Review
- Adeno-Associated Virus Gene Therapy for Spinal Muscular Atrophy Induces Hepatotoxicity via Cytokine and Macrophage Activation.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Transient prophylactic immunosuppression with abatacept or dasatinib prevents immune responses in AAV gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Challenging the more-is-better dogma: A precision-optimized AAV gene therapy for SMA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- RNA Therapeutics Targeting Skeletal Muscle: Emerging Antisense and Gene-Modifying Strategies.Biomolecules · 2026Review
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- 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
- Distinguishing Pseudotransduction and True Transduction Enables Characterization and Bioengineering of Extracellular Vesicle-Adeno-Associated Virus Vectors.Journal of extracellular vesicles · 2026Article
- Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026Review
- Identification of computationally designed skeletal and cardiac promoters with high specificity across AAV delivery routes.BMC biotechnology · 2026Article
- Sirolimus for the treatment of steroid-refractory hepatotoxicity following AAV gene therapy in patients with Duchenne muscular dystrophy.Journal of neuromuscular diseases · 2026Article
- DNA damage/p53, innate immune, and unfolded protein responses are activated in primate liver after toxic, high-dose AAV-SMN1 delivery.Molecular therapy. Advances · 2026Article
- Signal Peptide Engineering and Codon Optimization to Enhance α-Gal A Activity for rAAV Gene Therapy of Fabry Disease.Journal of inherited metabolic disease · 2026Article
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Contaminating plasmid sequences and disrupted vector genomes in the liver following adeno-associated virus gene therapy.Nature medicine · 2026Article
- Transcriptional changes in non-human primate tissues after intrathecal delivery of serotype 9 adeno-associated viral vector: Insights into organ toxicities.Molecular therapy. Methods & clinical development · 2025Article
- AAV-PHP.eB achieves superior neuronal transduction over AAV9 in pigtail macaques following intracerebroventricular administration.Molecular therapy. Methods & clinical development · 2025Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We analyzed retrospective data from toxicology studies involving administration of high doses of adeno-associated virus expressing different therapeutic transgenes to 21 cynomolgus and 15 rhesus macaques. We also conducted prospective studies to investigate acute toxicity following high-dose systemic administration of enhanced green fluorescent protein-expressing adeno-associated virus to 10 rhesus macaques. Toxicity was characterized by transaminitis, thrombocytopenia, and alternative complement pathway activation that peaked on post-administration day 3. Although most animals recovered, some developed ascites, generalized edema, hyperbilirubinemia, and/or coagulopathy that prompted unscheduled euthanasia. Study endpoint livers from animals that recovered and from unscheduled necropsies of those that succumbed to toxicity were analyzed via hypothesis-driven histopathology and unbiased single-nucleus RNA sequencing. All liver cell types expressed high transgene transcript levels at early unscheduled timepoints that subsequently decreased. Thrombocytopenia coincided with sinusoidal platelet microthrombi and sinusoidal endothelial injury identified via immunohistology and single-nucleus RNA sequencing. Acute toxicity, sinusoidal injury, and liver platelet sequestration were similarly observed with therapeutic transgenes and enhanced green fluorescent protein at doses ≥1 × 10
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