School of Biomedical Sciences, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, China.
State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, China.
Metab Brain Dis. 2021 Jan;36(1):45-52. doi: 10.1007/s11011-020-00630-2. Epub 2020 Nov 17.
Central nervous system (CNS) diseases are some of the most difficult to treat because the blood-brain barrier (BBB) almost entirely limits the passage of many therapeutic drugs into the CNS. Gene therapy based on the adeno-associated virus (AAV) vector has the potential to overcome this problem. For example, an AAV serotype AAV9 has been widely studied for its ability to cross the BBB to transduce astrocytes, but its efficiency is limited. The emergence of AAV directed evolution technology provides a solution, and the variants derived from AAV9 directed evolution have been shown to have significantly higher crossing efficiency than AAV9. However, the mechanisms by which AAV crosses the BBB are still unclear. In this review, we focus on recent advances in crossing the blood-brain barrier with AAV vectors. We first review the AAV serotypes that can be applied to treating CNS diseases. Recent progress in possible AAV crossing the BBB and transduction mechanisms are then summarized. Finally, the methods to improve the AAV transduction efficiency are discussed.
中枢神经系统（CNS）疾病是最难治疗的疾病之一，因为血脑屏障（BBB）几乎完全限制了许多治疗药物进入 CNS。基于腺相关病毒（AAV）载体的基因治疗有潜力克服这个问题。例如，AAV 血清型 AAV9 因其能够穿过 BBB 转导星形胶质细胞的能力而被广泛研究，但它的效率有限。AAV 定向进化技术的出现提供了一个解决方案，并且源自 AAV9 定向进化的变体已被证明具有比 AAV9 更高的穿越效率。然而，AAV 穿越 BBB 的机制仍不清楚。在这篇综述中，我们重点介绍了 AAV 载体穿越血脑屏障的最新进展。我们首先回顾了可用于治疗 CNS 疾病的 AAV 血清型。然后总结了最近在 AAV 穿越 BBB 和转导机制方面的进展。最后，讨论了提高 AAV 转导效率的方法。
