ArticleMolecular therapy. Methods & clinical development2025
Intracranial AAV administration dose-dependently recruits B cells to inhibit the AAV redosing.
Article in Molecular therapy. Methods & clinical development, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Bio-inspired polyphenol-polyelectrolyte WRAP system for geometrically controlled AAV delivery in diverse anatomical sites.Materials today. Bio · 2026Article
- Re-administration of AAV-mediated gene therapy for OTOF-related deafness: a single-arm trial.Nature medicine · 2026Article
- Attenuating AAV-triggered innate immunity in the adult mouse nervous systemActa pharmaceutica Sinica. B · 2026Article
- NeuroD1 gene therapy inhibits glioma growth and extends life span throughMolecular therapy. Oncology · 2026Article
- AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges.Frontiers in aging neuroscience · 2026Review
- Modified AAV5 capsid for improved brain biodistribution following direct injection in preclinical models.Molecular therapy. Methods & clinical development · 2025Article
- Redosing of AAV vectors in the brain after intracranial injections: Low-ish hanging fruit?Molecular therapy. Methods & clinical development · 2025Article
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Authors and funding
11 authors.
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Abstract
Recombinant adeno-associated virus (rAAV) is a widely used viral vector for gene therapy. However, a limitation of AAV-mediated gene therapy is that patients are typically dosed only once. In this study, we investigated the possibility of delivering multiple rounds of AAV through intracerebral injections in the mouse brain, and discovered a dose-dependent modulation of the second administration by the first-round AAV injection in a brain-wide scale. High-dose AAV injection increased chemokines CXCL9 and CXCL10 to recruit parenchymal infiltration of lymphocytes, whereas the blood-brain-barrier was relatively intact. Brain-wide dissection discovered the likely routes of the infiltrated lymphocytes through perivascular space and ventricles. Further analysis revealed that B lymphocytes played a critical role in inhibiting the redose. Choosing the right dosage for the first injection or switching the second AAV to a different serotype provided an effective way to antagonize the first-round AAV inhibition. Together, these results suggest that mammalian brains are not immunoprivileged for AAV infection, but multiple rounds of AAV gene therapy are feasible if designed carefully with proper doses and serotypes.
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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.