2. Academic Validation
  3. Dynein-regulated brain transduction of AAV.CAP-B10 via cerebral lateral ventricle enhances hippocampal function after traumatic brain injury through Ngf gene delivery in mice

Dynein-regulated brain transduction of AAV.CAP-B10 via cerebral lateral ventricle enhances hippocampal function after traumatic brain injury through Ngf gene delivery in mice

  • Exp Neurol. 2025 Sep:391:115285. doi: 10.1016/j.expneurol.2025.115285.
Jiang-Chang Wang 1,  Sheng-Hao Ding 2,  Zheng-Hui He 1,  Jia-Lin Huang 1,  Wei-Ji Weng 1,  Ying-Wei Gao 1,  Ji-Yao Jiang 3,  Yong Lin 4,  Jun-Feng Feng 5
Affiliations

Affiliations

  • 1 Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China; Shanghai Institute of Head Trauma, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China.
  • 2 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China.
  • 3 Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China; Shanghai Institute of Head Trauma, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China; Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China.
  • 4 Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China; Shanghai Institute of Head Trauma, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China. Electronic address: yonglin1996@hotmail.com.
  • 5 Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China; Shanghai Institute of Head Trauma, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China; Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China. Electronic address: fengjfmail@163.com.
PMID: 40348051 DOI: 10.1016/j.expneurol.2025.115285
Abstract

The blood-brain barrier (BBB) poses a significant challenge for the intravenous delivery of drugs targeting central nervous system (CNS) diseases. Recently, a novel adeno-associated virus (AAV)-9 variant, AAV.CAP-B10, has shown promise due to its high BBB-crossing efficiency and low liver toxicity. However, its strain dependency, ability to transduce the brain following cerebral lateral ventricle (CLV) injection, and underlying mechanisms remain unclear. In this study, we intravenously administered AAV.CAP-B10 to C57BL/6 and BALB/c mice to evaluate its ability to cross the BBB. We also injected AAV.CAP-B10 into the CLV of both mouse strains to assess brain transduction and explored its mechanisms using ciliobrevin D, a dynein inhibitor. Additionally, we tested whether AAV.CAP-B10 could deliver the nerve growth factor (Ngf) gene to treat traumatic brain injury (TBI) in mice. Our results showed that intravenous AAV.CAP-B10 effectively crossed the BBB in C57BL/6 mice but not in BALB/c mice. Brain transduction via CLV was significantly reduced in ciliobrevin D-treated mice, implicating dynein in this process. Furthermore, AAV.CAP-B10-mediated Ngf gene expression improved hippocampal function in TBI mice. These findings highlight the strain-dependent BBB penetration of AAV.CAP-B10, its dynein-associated hippocampal transduction via CLV, and its potential as a therapeutic gene vector for TBI treatment.

Keywords

AAV.CAP-B10; Blood-brain barrier; Cerebrospinal fluid; Dynein inhibitor; Ependymal cells.

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