High-titer AAV disrupts cerebrovascular integrity and induces lymphocyte infiltration in adult mouse brain.

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

SUBMITTER: Guo Y 

PROVIDER: S-EPMC10518493 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature