ArticleJournal of virology2020
Coevolution of Adeno-associated Virus Capsid Antigenicity and Tropism through a Structure-Guided Approach.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis 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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings.Frontiers in medicine · 2021Pooled it
- Natural and evolved membrane-associated accessory proteins differentially engage SNARE machinery for AAV egress.Journal of virology · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Exploration of genes and identification of evolutionary evidence in adeno-associated viruses.Journal of microbiology (Seoul, Korea) · 2026Article
- Complete neutralizing antibody evasion by serodivergent non-mammalian AAVs enables gene therapy redosing.Cell reports. Medicine · 2025Article
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- An ADAR2-mimic base editor for efficient C-to-U RNA editing in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries.Nature biomedical engineering · 2025Article
- Mechanisms of AAV neutralization by human alpha-defensins.PLoS pathogens · 2025Article
- Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Structural characterization of antibody-responses following Zolgensma treatment for AAV capsid engineering to expand patient cohorts.Nature communications · 2025Article
- Challenges in Humoral Immune Response to Adeno-Associated Viruses Determination.International journal of molecular sciences · 2025Review
- Structural studies of Parvoviridae capsid assembly and evolution: implications for novel AAV vector design.Frontiers in artificial intelligence · 2025Review
- Identification of a novel neutralization epitope in rhesus AAVs.Molecular therapy. Methods & clinical development · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.Nature communications · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.International journal of nanomedicine · 2024Review
- Redirecting AAV vectors to extrahepatic tissues.Molecular therapy : the journal of the American Society of Gene Therapy · 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
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Adeno-associated viruses (AAV) are composed of nonenveloped, icosahedral protein shells that can be adapted to package and deliver recombinant therapeutic DNA. Approaches to engineer recombinant capsids for gene therapy applications have focused on rational design or library-based approaches that can address one or two desirable attributes; however, there is an unmet need to comprehensively improve AAV vector properties. Such cannot be achieved by utilizing sequence data alone but requires harnessing the three-dimensional (3D) structural properties of AAV capsids. Here, we solve the structures of a natural AAV isolate complexed with antibodies using cryo-electron microscopy and harness this structural information to engineer AAV capsid libraries through saturation mutagenesis of different antigenic footprints. Each surface loop was evolved by infectious cycling in the presence of a helper adenovirus to yield a new AAV variant that then serves as a template for evolving the next surface loop. This stepwise process yielded a humanized AAV8 capsid (AAVhum.8) displaying nonnatural surface loops that simultaneously display tropism for human hepatocytes, increased gene transfer efficiency, and neutralizing antibody evasion. Specifically, AAVhum.8 can better evade neutralizing antisera from multiple species than AAV8. Further, AAVhum.8 displays robust transduction in a human liver xenograft mouse model with expanded tropism for both murine and human hepatocytes. This work supports the hypothesis that critical properties, such as AAV capsid antibody evasion and tropism, can be coevolved by combining rational design and library-based evolution for clinical gene therapy.
Indexed as
Identifiers
What Socratic 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 Socratic graph.