Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, China.
Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Adv Neurobiol. 2024;41:91-112. doi: 10.1007/978-3-031-69188-1_4.
Recombinant adeno-associated viruses (AAVs) have emerged as a popular tool for gene therapy in the central nervous system (CNS). Given the dense vasculature in the CNS, systemic administration is an appealing approach for achieving a broad distribution of AAV vectors across the CNS. However, the blood-brain barrier (BBB) is a major obstacle that blocks the entry of AAV vectors into the brain and spinal cord. Thus, there is a great need to develop novel AAV vector technology with enhanced BBB penetration. In this chapter, we briefly summarize AAV biology, possible mechanisms for AAV vectors to overcome the BBB and further engineering strategies, and current clinical trials using systemic AAV gene therapy for CNS diseases.
重组腺相关病毒（AAV）已成为中枢神经系统（CNS）基因治疗的一种流行工具。鉴于 CNS 中密集的血管系统，全身给药是实现 AAV 载体在 CNS 中广泛分布的一种有吸引力的方法。然而，血脑屏障（BBB）是阻止 AAV 载体进入大脑和脊髓的主要障碍。因此，非常有必要开发具有增强 BBB 穿透能力的新型 AAV 载体技术。在本章中，我们简要总结了 AAV 的生物学特性、AAV 载体克服 BBB 的可能机制以及进一步的工程策略，以及目前使用全身 AAV 基因治疗 CNS 疾病的临床试验。
