ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- METTL3-mediated m6A modification of circMtmr7 contributes to paclitaxel-induced peripheral neuropathy in the dorsal horn.The Journal of physiology · 2026Article
- Organoids - the future of pre-clinical development of AAV gene therapy for CNS disorders.Gene therapy · 2026Review
- Organoid Brain-Machine-Interface Devices for Central Nervous System Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Muscle-Specific DNM2 Overexpression Improves Charcot-Marie-Tooth Disease In Vivo and Reveals a Narrow Therapeutic Window in Skeletal Muscle.International journal of molecular sciences · 2026Article
- AAV delivery of artificial miRNA targeting MAPT for the reduction of tau pathology in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Key Challenges and Optimization Practices for Non-clinical Evaluation of AAV based Gene Therapy for Central Nervous System Disease.Pharmaceutical research · 2025Review
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Expression-based selection identifies a microglia-tropic AAV capsid for direct and CSF routes of administration in mice.bioRxiv : the preprint server for biology · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies.
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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.