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• W3110799080 abstract "Rationale: The blood-brain barrier (BBB) prevents the effective delivery of therapeutic molecules to the central nervous system (CNS). A recently generated adeno-associated virus (AAV)-based vector, AAV-PHP.eB, has been found to penetrate the BBB more efficiently than other vectors including AAV-PHP.B. However, little is known about the mechanisms. In this study, we investigated how AAV-PHP.eB penetrates the BBB in mice. Methods: We injected AAV-PHP.eB into the bloodstream of wild-type C57BL/6 and BALB/c mice as well as mouse strains carrying genetic mutation in apolipoprotein E gene (Apoe) or low-density lipoprotein receptor gene (Ldlr), or lacking various components of the immune system. Then, we evaluated AAV-PHP.eB transduction to the brain and spinal cord in these mice. Results: We found that the transduction to the CNS of intravenous AAV-PHP.eB was more efficient in C57BL/6 than BALB/c mice, and significantly reduced in Apoe or Ldlr knockout C57BL/6 mice compared to wild-type C57BL/6 mice. Moreover, poor CNS transduction in BALB/c mice was dramatically increased by B-cell or natural killer-cell depletion. Conclusions: Our findings demonstrate that the ApoE-LDLR pathway underlies the CNS tropism of AAV-PHP.eB and that the immune system contributes to the strain specificity of AAV-PHP.eB." @default.
• W3110799080 created "2020-12-21" @default.
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• W3110799080 date "2021-01-01" @default.
• W3110799080 modified "2023-09-29" @default.
• W3110799080 title "Apolipoprotein E, low-density lipoprotein receptor, and immune cells control blood-brain barrier penetration by AAV-PHP.eB in mice" @default.
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• W3110799080 doi "https://doi.org/10.7150/thno.46992" @default.
• W3110799080 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7738887" @default.
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• W3110799080 hasPublicationYear "2021" @default.
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