ArticleMolecular therapy. Nucleic acids2022
Directed evolution of adeno-associated virus 5 capsid enables specific liver tropism.
Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- QSP model for AAV-mediated antibody delivery in rat brain.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Efficient targeting of human glial progenitor cells in vivo with engineered AAV vectors and glymphatic delivery.Nature biotechnology · 2026Article
- Prevalence of pre-existing neutralizing antibodies to AAV5 and AAV8 in patients with Wilson's disease.Molecular therapy. Advances · 2026Article
- Receptor-guided AAV Tropism Engineering via MATCH.bioRxiv : the preprint server for biology · 2026Article
- Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer's disease in multiple mouse models.Genes & diseases · 2026Article
- AAV Capsid Modification and Its Influence on Viral Protein Stoichiometry and Packaging Fitness: Current Understandings and Future Direction.Molecular biotechnology · 2026Review
- Global seroprevalence of neutralizing and total antibodies against AAV vectors and their impact on the clinical gene therapy landscape: a scoping review.Frontiers in medicine · 2026Review
- Identification of AAV variants with improved transduction of human vascular endothelial cells by screening AAV capsid libraries in non-human primates.Gene therapy · 2025Article
- BDNF gene therapy rescues neuronal function via unique and common transcriptional responses in Aβ and tau-driven Alzheimer's disease mouse models.Biochemistry and biophysics reports · 2025Article
- Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.Journal of medical virology · 2025Review
- Distinct infectivity and neutralization antibody responses in the highly homologous AAV Go.1 and AAV5.Frontiers in medicine · 2025Article
- Adeno-Associated Virus 5 Protein Particles Produced byACS synthetic biology · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- Characterizing Glycosylation of Adeno-Associated Virus Serotype 9 Capsid Proteins Generated from HEK293 Cells through Glycopeptide Mapping and Released Glycan Analysis.Microorganisms · 2024Article
- Optimal trade-off control in machine learning-based library design, with application to adeno-associated virus (AAV) for gene therapy.Science advances · 2024Article
- Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.International journal of nanomedicine · 2024Review
- Pooled screening with next-generation gene editing tools.Current opinion in biomedical engineering · 2023Article
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impressive achievements in clinical trials to treat hemophilia establish a milestone in the development of gene therapy. It highlights the significance of AAV-mediated gene delivery to liver. AAV5 is a unique serotype featured by low neutralizing antibody prevalence. Nevertheless, its liver infectivity is relatively weak. Consequently, it is vital to exploit novel AAV5 capsid mutants with robust liver tropism. To this aim, we performed AAV5-NNK library and barcode screening in mice, from which we identified one capsid variant, called AAVzk2. AAVzk2 displayed a similar yield but divergent post-translational modification sites compared with wild-type serotypes. Mice intravenously injected with AAVzk2 demonstrated a stronger liver transduction than AAV5, roughly comparable with AAV8 and AAV9, with undetectable transduction of other tissues or organs such as heart, lung, spleen, kidney, brain, and skeletal muscle, indicating a liver-specific tropism. Further studies showed a superior human hepatocellular transduction of AAVzk2 to AAV5, AAV8 and AAV9, whereas the seroreactivity of AAVzk2 was as low as AAV5. Overall, we provide a novel AAV serotype that facilitates a robust and specific liver gene delivery to a large population, especially those unable to be treated by AAV8 and AAV9.
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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.