ArticleHuman gene therapy2023
Complement Activation by Adeno-Associated Virus-Neutralizing Antibody Complexes.
Article in Human gene therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 35 citations in OpenAlex.
- Automated zonal-rotor CsCl ultracentrifugation with ÄKTA-based fractionation removes empty and intermediate AAV capsids.Molecular therapy. Advances · 2026Article
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Decoding Nonlinearities in AAV-Based Gene Therapy Using PBPK Modelling.The AAPS journal · 2026Article
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 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
- Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026Review
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Advances in hydrogel-mediated gene therapy in ophthalmology: future directions and therapeutic potential.Regenerative biomaterials · 2026Review
- A Longitudinal 3D Live-Cell Imaging Platform to Uncover AAV Vector-Host Dynamics at Single-Cell Resolution.International journal of molecular sciences · 2025Article
- Impact of pre-existing immunity on safety and biodistribution of a single AAV9 vector intrathecal injection in cynomolgus monkeys.Molecular therapy. Methods & clinical development · 2025Article
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Innate immune response to AAV-based gene therapy vectors: Mechanisms of complement activation and cytokine release.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
- Complement activation in a phase Ib study of fordadistrogene movaparvovec for Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A myotropic AAV vector combined with skeletal muscleMolecular therapy. Methods & clinical development · 2025Article
- Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.Journal of medical virology · 2025Review
- Emerging Thrombotic Disorders Associated with Virus-Based Innovative Therapies: From VITT to AAV Gene Therapy-Related Thrombotic Microangiopathy.Thrombosis and haemostasis · 2025Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain.Nature communications · 2025Article
- Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment of monogenetic disorders using vectors based on adeno-associated virus (AAV) is an area of intense interest. AAV is non-pathogenic human virus, and preexisting capsid antibodies are prevalent in the population posing a challenge to the safety and efficacy of AAV-mediated gene therapies. In this study, we investigated the risk of AAV-mediated complement activation when sera from a cohort of human donors were exposed to AAV9 capsid. Seropositive donor sera carrying neutralizing antibodies from a previous environmental exposure activated complement when admixed with AAV9 capsids and complement activation was associated with donors who had higher levels of anti-AAV IgG1 antibodies. These findings were consistent with mass spectrometry analysis that identified increased binding of immunoglobulins and complement factors when AAV9 capsids were admixed with seropositive sera. Finally, complement activation was abrogated after IgG-depletion using affinity columns or serum pretreatment with an IgG degrading enzyme. Overall, these results demonstrate an important role of preexisting neutralizing antibodies in activating complement; a risk that can be mitigated by using adequate immunosuppression strategies when dosing seropositive patients with vector.
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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.