Intracranial AAV administration dose-dependently recruits B cells to inhibit the AAV redosing.

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

SUBMITTER: Xu Y 

PROVIDER: S-EPMC11874542 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature