ArticlePloS one2019
Clade F AAVHSCs cross the blood brain barrier and transduce the central nervous system in addition to peripheral tissues following intravenous administration in nonhuman primates.
Article in PloS one, 2019. 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, 25 citations in OpenAlex.
- Developing a minimally invasive gene therapy for multiple sclerosis.Molecular therapy. Methods & clinical development · 2025Article
- A comprehensive study of AAV tropism across C57BL/6 mice, BALB/c mice, and crab-eating macaques.Molecular therapy. Methods & clinical development · 2025Article
- Brain-targeting drug delivery systems: The state of the art in treatment of glioblastoma.Materials today. Bio · 2025Review
- Adeno-associated Virus-Mediated Gene Delivery Across the Blood-Brain Barrier.Advances in neurobiology · 2024Review
- Nuclease-free precise genome editing corrects MECP2 mutations associated with Rett syndrome.Frontiers in genome editing · 2024Article
- A novel dual-plasmid platform provides scalable transfection yielding improved productivity and packaging across multiple AAV serotypes and genomes.Molecular therapy. Methods & clinical development · 2023Article
- Single Systemic Administration of a Gene Therapy Leading to Disease Treatment in Metachromatic LeukodystrophyThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Variants of the adeno-associated virus serotype 9 with enhanced penetration of the blood-brain barrier in rodents and primates.Nature biomedical engineering · 2022Article
- Natural variations in AAVHSC16 significantly reduce liver tropism and maintain broad distribution to periphery and CNS.Molecular therapy. Methods & clinical development · 2022Article
- Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases.Frontiers in molecular neuroscience · 2022Review
- Considerations When Developing Blood-Brain Barrier Crossing Drug Delivery Technology.Handbook of experimental pharmacology · 2022Review
- Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning.Molecular therapy. Methods & clinical development · 2021Article
- Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord.Frontiers in molecular neuroscience · 2021Review
- Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies.Frontiers in cellular neuroscience · 2021Review
- Nucleic acid therapeutics in neurodevelopmental disease.Current opinion in genetics & development · 2020Review
- Adeno-Associated Virus and Hematopoietic Stem Cells: The Potential of Adeno-Associated Virus Hematopoietic Stem Cells in Genetic Medicines.Human gene therapy · 2020Review
- Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.Frontiers in medicine · 2020Review
- Molecular characterization of precise in vivo targeted gene integration in human cells using AAVHSC15.PloS one · 2020Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biodistribution of AAVHSC7, AAVHSC15, and AAVHSC17 following systemic delivery was assessed in cynomolgus macaques (Macaca fascicularis). Animals received a single intravenous (IV) injection of a self-complementary AAVHSC-enhanced green fluorescent protein (eGFP) vector and tissues were harvested at two weeks post-dose for anti-eGFP immunohistochemistry and vector genome analyses. IV delivery of AAVHSC vectors produced widespread distribution of eGFP staining in glial cells throughout the central nervous system, with the highest levels seen in the pons and lateral geniculate nuclei (LGN). eGFP-positive neurons were also observed throughout the central and peripheral nervous systems for all three AAVHSC vectors including brain, spinal cord, and dorsal root ganglia (DRG) with staining evident in neuronal cell bodies, axons and dendritic arborizations. Co-labeling of sections from brain, spinal cord, and DRG with anti-eGFP antibodies and cell-specific markers confirmed eGFP-staining in neurons and glia, including protoplasmic and fibrous astrocytes and oligodendrocytes. For all capsids tested, 50 to 70% of glial cells (S100-β+) and on average 8% of neurons (NeuroTrace+) in the LGN were positive for eGFP expression. In the DRG, 45 to 62% of neurons and 8 to 12% of satellite cells were eGFP-positive for the capsids tested. eGFP staining was also observed in peripheral tissues with abundant staining in hepatocytes, skeletal- and cardio-myocytes and in acinar cells of the pancreas. Biodistribution of AAVHSC vector genomes in the central and peripheral organs generally correlated with eGFP staining and were highest in the liver for all AAVHSC vectors tested. These data demonstrate that AAVHSCs have broad tissue tropism and cross the blood-nerve and blood-brain-barriers following systemic delivery in nonhuman primates, making them suitable gene editing or gene transfer vectors for therapeutic application in human genetic diseases.
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