ArticleMolecular therapy. Methods & clinical development2021
Directed Evolution of AAV Serotype 5 for Increased Hepatocyte Transduction and Retained Low Humoral Seroreactivity.
Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Defining the safety and efficacy of liver-directed AAV gene therapy using a human liver tissue-equivalent platform.Molecular therapy. Advances · 2026Article
- Engineering novel AAV capsids by broadly attenuated and subsequent muscle-specific tropism in mice and NHPs.Molecular therapy. Advances · 2026Article
- Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026Review
- An Expanded Toolbox for Versatile Chemical Editing of Adeno-Associated Virus.Angewandte Chemie (International ed. in English) · 2026Article
- A facile chemical strategy to synthesize precise AAV-protein conjugates for targeted gene delivery.Molecular therapy. Oncology · 2025Article
- Review
- Challenges in Humoral Immune Response to Adeno-Associated Viruses Determination.International journal of molecular sciences · 2025Review
- Distinct infectivity and neutralization antibody responses in the highly homologous AAV Go.1 and AAV5.Frontiers in medicine · 2025Article
- Systematic multi-trait AAV capsid engineering for efficient gene delivery.Nature communications · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- Chemical approaches to probe and engineer AAV vectors.Nanoscale · 2024Review
- Comparative in vivo characterization of newly discovered myotropic adeno-associated vectors.Skeletal muscle · 2024Article
- Characterization of a Bioengineered AAV3B Capsid Variant with Enhanced Hepatocyte Tropism and Immune Evasion.Human gene therapy · 2023Article
- Cross-Species Permissivity: Structure of a Goat Adeno-Associated Virus and Its Complex with the Human Receptor AAVR.Journal of virology · 2022Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Targeting the lung epithelium after intravenous delivery by directed evolution of underexplored sites on the AAV capsid.Molecular therapy. Methods & clinical development · 2022Article
- Directed evolution of adeno-associated virus 5 capsid enables specific liver tropism.Molecular therapy. Nucleic acids · 2022Article
- CRISPR/Cas therapeutic strategies for autosomal dominant disorders.The Journal of clinical investigation · 2022Review
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
- Human Hepatocyte Transduction with Adeno-Associated Virus Vector.Methods in molecular biology (Clifton, N.J.) · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most recombinant adeno-associated virus (AAV) capsids utilized in liver gene therapy have significant levels of pre-existing neutralizing antibodies in the human population. These neutralizing factors limit the patient pools eligible for receiving AAV-mediated therapies. AAV serotype 5 (AAV5) does not face the same barrier of humoral immunity as most AAV serotypes due to its low seroprevalence. However, AAV5 can only facilitate a low level of transgene expression in the liver, constraining its application to a small number of liver diseases. To improve the liver transduction of AAV5 while retaining its low seroprevalence, we constructed a library of AAV5 mutants via random mutagenesis and screened in Huh7 cells. Two molecularly evolved AAV5 variants, MV50 and MV53, demonstrated significantly increased transduction efficiency in Huh7 cells (∼12×) and primary human hepatocytes (∼10×). All variants had retained low seroreactivity toward pooled human immunoglobulin G (IgG) when compared to AAV5, which was significantly less seroreactive than AAV9. Functional characterization of the mutants also revealed insights into the functions of various domains, especially the VR-I, in the AAV5 capsid. The result is AAV5 variant capsids with much enhanced human hepatocyte transduction, potentially useful for liver-directed 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.