A novel strategy for delivering Niemann-Pick type C2 proteins across the blood-brain barrier using the brain endothelial-specific AAV-BR1 virus.

ABSTRACT: Treating central nervous system (CNS) diseases is complicated by the incapability of numerous therapeutics to cross the blood-brain barrier (BBB), mainly composed of brain endothelial cells (BECs). Genetically modifying BECs into protein factories that supply the CNS with recombinant proteins is a promising approach to overcome this hindrance, especially in genetic diseases, like Niemann Pick disease type C2 (NPC2), where both CNS and peripheral cells are affected. Here, we investigated the potential of the BEC-specific adeno-associated viral vector (AAV-BR1) encoding NPC2 for expression and secretion from primary BECs cultured in an in vitro BBB model with mixed glial cells, and in healthy BALB/c mice. Transduced primary BECs had significantly increased NPC2 gene expression and secreted N

SUBMITTER: Rasmussen CLM 

PROVIDER: S-EPMC10084444 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature