ReviewDrugs2023
Mitigating Serious Adverse Events in Gene Therapy with AAV Vectors: Vector Dose and Immunosuppression.
Review in Drugs, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed, 31 citations in OpenAlex.
- VTX-PID as a novel recombinant immunoglobulin G-degrading enzyme (IdeS) for efficient AAV-based gene therapy in participants with neutralizing antibodies: results of the phase I first-in-human NAVIgATE study.Frontiers in immunology · 2026Trial
- BAG3 gene therapy emerges as a potential treatment for myofibrillar myopathies.Molecular therapy. Advances · 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
- Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Noninvasive longitudinal assessment of early-stage Duchenne muscular dystrophy: In vivo diaphragm imaging in mdx mice.Ultrasonics · 2026Article
- Treatment of spinal cord injury, by restoration of neuronal networks using a combination of surgery and KCL-286, an orally available retinoic acid receptor β drug.Frontiers in surgery · 2026Review
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Rapid detection of AAV8 binding antibodies in gene therapy candidates: development of a point-of-care approach.Gene therapy · 2025Article
- Gene therapy strategies for aging intervention.Cell insight · 2025Review
- Progress and Challenges in the Treatment of Fabry Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy.International journal of molecular sciences · 2025Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Cancer vaccines: an update on recent achievements and prospects for cancer therapy.Clinical and experimental medicine · 2024Review
- Preclinical evaluation of NG101, a potential AAV gene therapy for wet age-related macular degeneration.Molecular therapy. Methods & clinical development · 2024Article
- Engineered IgM and IgG cleaving enzymes for mitigating antibody neutralization and complement activation in AAV gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- White-to-Beige and Back: Adipocyte Conversion and Transcriptional Reprogramming.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Dose-response evaluation of intravenous gene therapy in a symptomatic mouse model of metachromatic leukodystrophy.Molecular therapy. Methods & clinical development · 2024Article
- Exploring delivery systems for targeted nanotechnology-based gene therapy in the inner ear.Therapeutic delivery · 2024Review
- Stimulus-Responsive Nanodelivery and Release Systems for Cancer Gene Therapy: Efficacy Improvement Strategies.International journal of nanomedicine · 2024Review
- AAV Immunotoxicity: Implications in Anti-HBV Gene Therapy.Microorganisms · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene transfer with high doses of adeno-associated viral (AAV) vectors has resulted in serious adverse events and even death of the recipients. Toxicity could most likely be circumvented by repeated injections of lower and less toxic doses of vectors. This has not been pursued as AAV vectors induce potent neutralizing antibodies, which prevent cell transduction upon reinjection of the same vector. This review discusses different types of immune responses against AAV vectors and how they offer targets for the elimination or inhibition of vector-specific neutralizing antibodies. Such antibodies can be circumvented by using different virus serotypes for sequential injections, they can be removed by plasmapheresis, or they can be destroyed by enzymatic degradation. Antibody producing cells can be eliminated by proteasome inhibitors. Drugs that inhibit T-cell responses, B-cell signaling, or presentation of the vector's antigens to B cells can prevent or reduce induction of AAV-specific antibodies. Combinations of different approaches and drugs are likely needed to suppress or eliminate neutralizing antibodies, which would then allow for repeated dosing. Alternatively, novel AAV vectors with higher transduction efficacy are being developed and may allow for a dose reduction, although it remains unknown if this will completely address the problem of high-dose adverse events.
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What OpenQuestion holds
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.