ArticleJCI insight2020
Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 3 of them syntheses that pooled it.
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
96 citing papers in PubMed, 3 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- What's new and what's next for gene therapy in Pompe disease?Expert opinion on biological therapy · 2022Pooled it
- rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis.Frontiers in immunology · 2022Pooled it
- Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings.Frontiers in medicine · 2021Pooled it
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- NF-κB-driven immune checkpoint knockdown and cytokine expression in cancer cells for tumor immunotherapy.iScience · 2026Article
- Rapamycin nanoparticles mitigate anti-AAV antibody formation in a mouse model of ornithine transcarbamylase deficiency.Molecular therapy. Advances · 2026Article
- RNA splicing and cardiovascular disease: a guide for cardiologists.European heart journal · 2026Review
- Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy.Clinical and translational medicine · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- AAV-based gene therapies for neovascular AMD.Gene therapy · 2026Review
- Ferumoxytol enhances NF-κB-responsive GBA-targeted ferroptosis gene therapy in acute myeloid leukemia.Journal of nanobiotechnology · 2026Article
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- Environmental and developmental factors shape anti-AAV immunity in pigs.Gene therapy · 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
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Identification and Characterization of Novel Human IgG-Degrading Enzymes.Biochemistry · 2026Article
- Liver Gene Therapy in Fabry Disease Mice With Low Doses of rAAV2/8 Expressing a Codon-Optimized hGLA cDNA Results in Long-Term Disease Correction.Journal of inherited metabolic disease · 2026Article
- Overcoming matrix effects in AAV neutralization assays with a constant serum concentration approach.Gene therapy · 2026Article
- From molecular correction to functional rescue: delivery, tissue state, and immunobiology as the principal constraints on dystrophin-restoring therapy in Duchenne muscular dystrophy.Frontiers in pharmacology · 2026Review
- Advances in endothelial cell targeting by AAV vectors.Acta biochimica Polonica · 2026Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Preexisting humoral immunity to recombinant adeno-associated virus (AAV) vectors restricts the treatable patient population and efficacy of human gene therapies. Approaches to clear neutralizing antibodies (NAbs), such as plasmapheresis and immunosuppression, are either ineffective or cause undesirable side effects. Here, we describe a clinically relevant strategy to rapidly and transiently degrade NAbs before AAV administration using an IgG-degrading enzyme (IdeZ). We demonstrate that recombinant IdeZ efficiently cleaved IgG in dog, monkey, and human antisera. Prophylactically administered IdeZ cleaved circulating human IgG in mice and prevented AAV neutralization in vivo. In macaques, a single intravenous dose of IdeZ rescued AAV transduction by transiently reversing seropositivity. Importantly, IdeZ efficiently cleaved NAbs and rescued AAV transduction in mice passively immunized with individual human donor sera representing a diverse population. Our antibody clearance approach presents a potentially new paradigm for expanding the prospective patient cohort and improving efficacy of AAV gene therapy.
Indexed as
Identifiers
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.