ArticleMolecular neurobiology2019
Effects of Neutralizing Antibody Production on AAV-PHP.B-Mediated Transduction of the Mouse Central Nervous System.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
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- Re-administration of AAV-mediated gene therapy for OTOF-related deafness: a single-arm trial.Nature medicine · 2026Article
- Comparison of AAV9-driven motor neuron transduction following different CNS-directed delivery methods in mice.Scientific reports · 2026Article
- Ubiquitous and Brain Cell-Type-Specific Promoters and Enhancers in Lentiviral Vectors.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Genetic tools for imaging microcirculation via plasma labeling.Anatomical science international · 2025Review
- Blood-brain barrier-penetrant AAV vectors for cell type-specific gene expression in the mouse brain.Anatomical science international · 2025Review
- AAV-mediated inner ear gene delivery triggers mild host immune responses in the mammalian inner ear.Molecular therapy. Methods & clinical development · 2025Article
- Towards enhancing photostability and adeno-associated viral vector delivery for genetically encoded plasma fluorescent labels.Neurophotonics · 2025Article
- Improving cell-specific recombination using AAV vectors in the murine CNS by capsid and expression cassette optimization.Molecular therapy. Methods & clinical development · 2024Article
- Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates.Molecular therapy. Methods & clinical development · 2023Article
- Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans.Nature biomedical engineering · 2023Article
- LONRF2 is a protein quality control ubiquitin ligase whose deficiency causes late-onset neurological deficits.Nature aging · 2023Article
- A blood-brain barrier-penetrating AAV2 mutant created by a brain microvasculature endothelial cell-targeted AAV2 variant.Molecular therapy. Methods & clinical development · 2023Article
- Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo.Communications biology · 2022Article
- Liver-secreted fluorescent blood plasma markers enable chronic imaging of the microcirculation.Cell reports methods · 2022Article
- Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications.Cerebellum (London, England) · 2022Article
- A Confocal Microscopic Study of Gene Transfer into the Mesencephalic Tegmentum of Juvenile Chum Salmon,International journal of molecular sciences · 2021Article
- GABAergic neuron-specific whole-brain transduction by AAV-PHP.B incorporated with a new GAD65 promoter.Molecular brain · 2021Article
- Toward Development of Neuron Specific Transduction After Systemic Delivery of Viral Vectors.Frontiers in neurology · 2021Article
- CHIP as a therapeutic target for neurological diseases.Cell death & disease · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV serotype 9, is highly permeable to the blood-brain barrier. A major obstacle to the systemic use of AAV-PHP.B is the generation of neutralizing antibodies (NAbs); however, temporal profiles of NAb production after exposure to AAV-PHP.B, and the influence on later AAV-PHP.B administration, remains unknown. To address these, AAV-PHP.Bs expressing either GFP or mCherry by neuron-specific or astrocyte-specific promoters were intravenously administered to mice at various intervals, and brain expression was examined. Injection of two AAV-PHP.Bs, separated temporally, showed that as little as a 1-day interval between injections resulted in a significant decrease in expression of the second transgene, with a complete loss of expression after 7 days, paralleling an increase in serum NAb titers. Brain parenchymal injection was explored to circumvent the presence of NAbs. Mice systemically pre-treated with an AAV-PHP.B were injected intra-cerebrally with an AAV-PHP.B expressing GFP. After 2 weeks, marked GFP expression in the cerebellum was evident, showing that pre-existing NAbs did not affect the AAV-PHP.B directly injected into the brain. In contrast, reversing the injection order, i.e., cerebellar injection followed by systemic injection, completely eliminated expression of the second transgene. We confirmed that intra-cerebellar injection produced NAbs in the serum, but not in the cerebrospinal fluid (CSF). Our results indicate that the preclusion of brain transduction by a second AAV-PHP.B administration begins from the first day following systemic injection and is established within 1 week. Serum NAbs can be avoided by directly injecting AAV-PHP.Bs into brain tissue.
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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.