ArticlePLoS biology2023
Targeting AAV vectors to the central nervous system by engineering capsid-receptor interactions that enable crossing of the blood-brain barrier.
Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 69 citations in OpenAlex.
- Next generation AAV-F capsid gene therapy rescues disease pathology in a model of pyruvate dehydrogenase complex deficiency.Molecular therapy. Advances · 2026Article
- AI-engineered AAV capsid enables intravitreal delivery for the treatment of diverse retinal degenerations.Molecular therapy. Advances · 2026Article
- Efficient targeting of human glial progenitor cells in vivo with engineered AAV vectors and glymphatic delivery.Nature biotechnology · 2026Article
- Intranasal versus intravenous AAV delivery: A comparative analysis of brain-targeting efficiency and peripheral exposure in mice.Gene therapy · 2026Article
- Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.Nature communications · 2026Article
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- Article
- Improvement of Adeno-Associated Virus (AAV)-Based Technologies by Cell-Penetrating Penta-Peptides (CPP5s).Pharmaceutics · 2026Review
- Enhancer-based gene therapy: a new path for precision medicine.Hereditas · 2026Review
- Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- Viral vector-based gene therapies in the clinic: An update.Bioengineering & translational medicine · 2026Review
- Impact and Significance of Viral Vectors for siRNA Delivery in the Treatment of Alzheimer's Disease.Current pharmaceutical biotechnology · 2026Review
- Article
- AAV-based gene therapy ameliorates neurological deficits in a mouse model of childhood-onset neurodegeneration with cerebellar atrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 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
- Synapsin III promotes neuronal-like transdifferentiation of glioblastoma stem cells by disrupting JAG1-Notch1 interaction.Neuro-oncology · 2025Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Highly conserved brain vascular receptor ALPL mediates transport of engineered AAV vectors across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene Therapy of Adrenomyeloneuropathy: Challenges, Target Cells, and Prospectives.Biomedicines · 2025Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Viruses have evolved the ability to bind and enter cells through interactions with a wide variety of cell macromolecules. We engineered peptide-modified adeno-associated virus (AAV) capsids that transduce the brain through the introduction of de novo interactions with 2 proteins expressed on the mouse blood-brain barrier (BBB), LY6A or LY6C1. The in vivo tropisms of these capsids are predictable as they are dependent on the cell- and strain-specific expression of their target protein. This approach generated hundreds of capsids with dramatically enhanced central nervous system (CNS) tropisms within a single round of screening in vitro and secondary validation in vivo thereby reducing the use of animals in comparison to conventional multi-round in vivo selections. The reproducible and quantitative data derived via this method enabled both saturation mutagenesis and machine learning (ML)-guided exploration of the capsid sequence space. Notably, during our validation process, we determined that nearly all published AAV capsids that were selected for their ability to cross the BBB in mice leverage either the LY6A or LY6C1 protein, which are not present in primates. This work demonstrates that AAV capsids can be directly targeted to specific proteins to generate potent gene delivery vectors with known mechanisms of action and predictable tropisms.
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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.