ArticleMolecular therapy. Methods & clinical development2023
High-titer AAV disrupts cerebrovascular integrity and induces lymphocyte infiltration in adult mouse brain.
Article in Molecular therapy. Methods & clinical development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Titer- and Intervention Timing-Dependent Functional Effects of AAV9-NeuroD1 Gene Therapy on Spinal Cord Injury.Current issues in molecular biology · 2026Article
- Efficient targeting of human glial progenitor cells in vivo with engineered AAV vectors and glymphatic delivery.Nature biotechnology · 2026Article
- Attenuating AAV-triggered innate immunity in the adult mouse nervous systemActa pharmaceutica Sinica. B · 2026Article
- NeuroD1-based in situ neural regeneration for the treatment of radiation-induced brain injury.Neural regeneration research · 2026Article
- Engineering novel AAV capsids by broadly attenuated and subsequent muscle-specific tropism in mice and NHPs.Molecular therapy. Advances · 2026Article
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- AAV-only targeting of ventral tegmental area dopamine neurons for optical self-stimulation studies in mice.Scientific reports · 2026Article
- In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression.Genome medicine · 2026Article
- Immune response to adeno-associated viral vectors in a human iPSC-derived microglia chimeric mouse model.Cell reports methods · 2026Article
- AAV.PHP.eB-based strategies for precise modulation of α7 nicotinic acetylcholine receptor in neurons and astrocytes in the adult mouse brain.Scientific reports · 2026Article
- GBA1 F213I mutation increases the expression of LCN2 promoting neurodegeneration.Cell death and differentiation · 2026Article
- AAV-only targeting of ventral tegmental area dopamine neurons for optical self-stimulation studies in mice.bioRxiv : the preprint server for biology · 2026Article
- A Closed-Loop-Capable Neural Interface Platform for Deep Brain Modulation via Integrated Non-Viral Gene Delivery, NIR Optogenetics, and Electrophysiological Recording.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- NDRG4 overexpression is associated with reduced apoptosis after intracerebral hemorrhage via the PI3K/Akt/GSK3β signaling pathway.Scientific reports · 2026Article
- Serotype-specific tropism of adeno-associated viruses in dorsal meningeal lymphatic vessels via intra-cisterna magna delivery.Frontiers in immunology · 2026Article
- Cytotoxic T lymphocytes and their dual role in modulating blood-brain barrier integrity in immune-mediated neurological pathologies.Journal of translational medicine · 2025Review
- A novel gene delivery platform based on a commensal human anellovirus demonstrates transduction in multiple tissue types.Molecular therapy. Methods & clinical development · 2025Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Brain Endothelial Cells in Blood-Brain Barrier Regulation and Neurological Therapy.International journal of molecular sciences · 2025Review
- AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain.Nature communications · 2025Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The brain is often described as an "immune-privileged" organ due to the presence of the blood-brain-barrier (BBB), which limits the entry of immune cells. In general, intracranial injection of adeno-associated virus (AAV) is considered a relatively safe procedure. In this study, we discovered that AAV, a popular engineered viral vector for gene therapy, can disrupt the BBB and induce immune cell infiltration in a titer-dependent manner. First, our bulk RNA sequencing data revealed that injection of high-titer AAV significantly upregulated many genes involved in disrupting BBB integrity and antiviral adaptive immune responses. By using histologic analysis, we further demonstrated that the biological structure of the BBB was severely disrupted in the adult mouse brain. Meanwhile, we noticed abnormal leakage of blood components, including immune cells, within the brain parenchyma of high-titer AAV injected areas. Moreover, we identified that the majority of infiltrated immune cells were cytotoxic T lymphocytes (CTLs), which resulted in a massive loss of neurons at the site of AAV injection. In addition, antagonizing CTL function by administering antibodies significantly reduced neuronal toxicity induced by high-titer AAV. Collectively, our findings underscore potential severe side effects of intracranial injection of high-titer AAV, which might compromise proper data interpretation if unaware of.
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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.