ArticleScience advances2018
Physical positioning markedly enhances brain transduction after intrathecal AAV9 infusion.
Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
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Who cites it
24 citing papers in PubMed.
- Efficient targeting of human glial progenitor cells in vivo with engineered AAV vectors and glymphatic delivery.Nature biotechnology · 2026Article
- A Head-to-Head Comparison of AAV9 Biodistribution in Mice: Routes of Administration and Age Dependence.Genes · 2026Article
- AAV2retro Enters Axons of Passage and Extensively Transduces Corticospinal Neurons After Injection into Spinal White Matter.Brain sciences · 2025Article
- Intrathecal administration of Anti-Nogo-A antibody in macaque monkeys: Pharmacokinetics, tissue penetration and target interaction.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
- In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Micro/nanosystems for controllable drug delivery to the brain.Innovation (Cambridge (Mass.)) · 2024Review
- Quantifying Dendritic Arbors In Vitro and In Vivo in Rodent Models.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Chemogenetic activation of ventral medullary astrocytes enhances feeding and corticosterone release in response to mild glucoprivation.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- An AAV capsid increases transduction of striatum and a ChAT promoter allows selective cholinergic neuron transduction.Molecular therapy. Methods & clinical development · 2023Article
- Insulin-like growth factor-2 is a promising candidate for the treatment and prevention of Alzheimer's disease.CNS neuroscience & therapeutics · 2023Review
- Assessment of AAV9 distribution and transduction in rats after administration through Intrastriatal, Intracisterna magna and Lumbar Intrathecal routes.Gene therapy · 2023Article
- Pre-clinical delivery of gene therapy products to the cerebrospinal fluid: challenges and considerations for clinical translation.Frontiers in molecular neuroscience · 2023Review
- Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.Journal of personalized medicine · 2022Review
- The glymphatic system: implications for drugs for central nervous system diseases.Nature reviews. Drug discovery · 2022Review
- Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases.Frontiers in molecular neuroscience · 2022Review
- The AAV9 Variant Capsid AAV-F Mediates Widespread Transgene Expression in Nonhuman Primate Spinal Cord After Intrathecal Administration.Human gene therapy · 2022Article
- Article
- Intersectional targeting of defined neural circuits by adeno-associated virus vectors.Journal of neuroscience research · 2021Review
- Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques.Frontiers in bioengineering and biotechnology · 2021Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Several neurological disorders may benefit from gene therapy. However, even when using the lead vector candidate for intrathecal administration, adeno-associated virus serotype 9 (AAV9), the strength and distribution of gene transfer to the brain are inconsistent. On the basis of preliminary observations that standard intrathecal AAV9 infusions predominantly drive reporter gene expression in brain regions where gravity might cause cerebrospinal fluid to settle, we tested the hypothesis that counteracting vector "settling" through animal positioning would enhance vector delivery to the brain. When rats are either inverted in the Trendelenburg position or continuously rotated after intrathecal AAV9 infusion, we find (i) a significant 15-fold increase in the number of transduced neurons, (ii) a marked increase in gene delivery to cortical regions, and (iii) superior animal-to-animal consistency of gene expression. Entorhinal, prefrontal, frontal, parietal, hippocampal, limbic, and basal forebrain neurons are extensively transduced: 95% of transduced cells are neurons, and greater than 70% are excitatory. These findings provide a novel and simple method for broad gene delivery to the cortex and are of substantial relevance to translational programs for neurological disorders, including Alzheimer's disease and related dementias, stroke, and traumatic brain injury.
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