ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Mapping the Structural Determinants Required for AAVrh.10 Transport across the Blood-Brain Barrier.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 79 citations in OpenAlex.
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- Age outweighs route for AAV-PHP.eB transgene distribution via inner ear delivery.Drug delivery and translational research · 2026Article
- Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026Review
- AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges.Frontiers in aging neuroscience · 2026Review
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- Cancer gene therapy: historical perspectives, current applications, and future directions.Functional & integrative genomics · 2025Review
- AAV-mediated peripheral scFv's administration to reduce cerebral tau in adult P301S transgenic mice: Mono-vs. combination therapy.Molecular therapy. Methods & clinical development · 2025Article
- Evaluation of AAV Capsids and Delivery Approaches for Hereditary Hemorrhagic Telangiectasia Gene Therapy.Translational stroke research · 2025Article
- RNA Structure: Past, Future, and Gene Therapy Applications.International journal of molecular sciences · 2024Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Evaluation of Aav Capsids and Delivery Approaches for Hereditary Hemorrhagic Telangiectasia Gene Therapy.Research square · 2024Article
- Review
- Liver directed adeno-associated viral vectors to treat metabolic disease.Journal of inherited metabolic disease · 2024Review
- Enhancing Antibody Exposure in the Central Nervous System: Mechanisms of Uptake, Clearance, and Strategies for Improved Brain Delivery.Journal of nanotheranostics · 2023Article
- Characterization and biodistribution of under-employed gene therapy vector AAV7.Journal of virology · 2023Article
- Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.Nature protocols · 2023Review
- AAV-iScience · 2023Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.Journal of personalized medicine · 2022Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Effective gene delivery to the CNS by intravenously administered adeno-associated virus (AAV) vectors requires crossing the blood-brain barrier (BBB). To achieve therapeutic CNS transgene expression, high systemic vector doses are often required, which poses challenges such as scale-up costs and dose-dependent hepatotoxicity. To improve the specificity and efficiency of CNS gene transfer, a better understanding of the structural features that enable AAV transit across the BBB is needed. We generated a combinatorial domain swap library using AAV1, a serotype that does not traverse the vasculature, and AAVrh.10, which crosses the BBB in mice. We then screened individual variants by phylogenetic and structural analyses and subsequently conducted systemic characterization in mice. Using this approach, we identified key clusters of residues on the AAVrh.10 capsid that enabled transport across the brain vasculature and widespread neuronal transduction in mice. Through rational design, we mapped a minimal footprint from AAVrh.10, which, when grafted onto AAV1, confers the aforementioned CNS phenotype while diminishing vascular and hepatic transduction through an unknown mechanism. Functional mapping of this capsid surface footprint provides a roadmap for engineering synthetic AAV capsids for efficient CNS gene transfer with an improved safety profile.
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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.