BBB-crossing adeno-associated virus vector: An excellent gene delivery tool for CNS disease treatment

• Published in: Journal of controlled release Vol. 333; pp. 129 - 138
• Main Authors: Chen, Wenli, Yao, Shun, Wan, Jie, Tian, Yu, Huang, Lan, Wang, Shanshan, Akter, Farhana, Wu, Yinqiu, Yao, Yizheng, Zhang, Xiaochun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-05-2021
• Subjects: Adeno-associated virus; BBB-crossing; Blood-brain barrier; CNS diseases; Gene therapy; Adeno-associated virus; AAVR; BBB; CREATE; BBB-crossing; CNS diseases; PKD; CNS; ITRs; Blood-brain barrier; PNS; AAV; NHPs; Gene therapy; TJs
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.03.029

The presence of the blood-brain barrier (BBB) remains a challenge in the treatment of central nervous system (CNS) diseases, as it hinders the infiltration of many therapeutic drugs into the brain parenchyma. Therefore, developing efficacious pharmacological agents that can traverse the BBB is crucial for optimal treatment of diseases of the CNS such as neurodegenerative conditions and brain tumors. Adeno-associated virus (AAV), one of the most promising gene therapy vectors, has been shown to cross the BBB safely and is non-pathogenic in nature and therefore has been utilized for numerous diseases of the CNS. Along with the development of protein engineering techniques such as directed evolution including DNA shuffling, a great number of BBB-crossing AAVs have been developed, that could be systemically injected for therapeutic benefit. In this review, we discuss several feasible approaches to improve transportation of therapeutic agents to the CNS. We also discuss the advantages of using BBB-crossing AAVs, their role as a gene delivery agent and highlight the different types of BBB-AAV vectors that have been developed in order to provide a greater insight into how they can be used in diseases of the CNS.
[Display omitted]
•BBB structure and the BBB-crossing strategies•AAV biology and BBB-crossing ability•Developing BBB-crossing ability enhanced AAV variants