ArticleProceedings of the National Academy of Sciences of the United States of America2017
Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 2 of them syntheses that pooled it.
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
150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 214 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
- Natural and evolved membrane-associated accessory proteins differentially engage SNARE machinery for AAV egress.Journal of virology · 2026Article
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- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Review
- Advances in endothelial cell targeting by AAV vectors.Acta biochimica Polonica · 2026Review
- Complete neutralizing antibody evasion by serodivergent non-mammalian AAVs enables gene therapy redosing.Cell reports. Medicine · 2025Article
- Preclinical Assessment of Mitochondrial-Targeted ND4 Gene Therapy for Leber Hereditary Optic Neuropathy.Investigative ophthalmology & visual science · 2025Article
- Directed evolution of novel AAV variants using the MCMS library for enhanced CNS tropism and reduced liver targeting in mice.Molecular therapy. Methods & clinical development · 2025Article
- Wild-type and engineered adeno-associated viral vectors produce comparable opsin expression and light-evoked responses in rat skeletal muscle.Molecular therapy. Methods & clinical development · 2025Article
- Dose-finding andMolecular therapy. Methods & clinical development · 2025Article
- AAV-mediated gene therapy for focal epilepsy by expressing neuropeptide Y and Y2 receptor in rodent and non-human primate hippocampus.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Programmable self-replicating JEV nanotherapeutics redefine RNA delivery in ALS.Communications biology · 2025Review
- Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries.Nature biomedical engineering · 2025Article
- Advances in viral vector-based delivery systems for gene therapy: a comprehensive review.3 Biotech · 2025Review
- Optimized genomic editing of a common Duchenne muscular dystrophy mutation in patient-derived muscle cells and a new humanized mouse model.Molecular therapy. Nucleic acids · 2025Article
- Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy.International journal of molecular sciences · 2025Review
90 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
9 authors at 2 institutions in 1 country.
Funding
Abstract
Preexisting neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) pose a major, unresolved challenge that restricts patient enrollment in gene therapy clinical trials using recombinant AAV vectors. Structural studies suggest that despite a high degree of sequence variability, antibody recognition sites or antigenic hotspots on AAVs and other related parvoviruses might be evolutionarily conserved. To test this hypothesis, we developed a structure-guided evolution approach that does not require selective pressure exerted by NAbs. This strategy yielded highly divergent antigenic footprints that do not exist in natural AAV isolates. Specifically, synthetic variants obtained by evolving murine antigenic epitopes on an AAV serotype 1 capsid template can evade NAbs without compromising titer, transduction efficiency, or tissue tropism. One lead AAV variant generated by combining multiple evolved antigenic sites effectively evades polyclonal anti-AAV1 neutralizing sera from immunized mice and rhesus macaques. Furthermore, this variant displays robust immune evasion in nonhuman primate and human serum samples at dilution factors as high as 1:5, currently mandated by several clinical trials. Our results provide evidence that antibody recognition of AAV capsids is conserved across species. This approach can be applied to any AAV strain to evade NAbs in prospective patients for human gene therapy.
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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.