腺相关病毒载体向脑内的递送:技术进展与临床应用
Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.
作者信息
Ye Dezhuang, Chukwu Chinwendu, Yang Yaoheng, Hu Zhongtao, Chen Hong
机构信息
Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, USA.
Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, USA; Department of Neurosurgery, Washington University School of Medicine, Saint Louis, MO 63110 USA; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
出版信息
Adv Drug Deliv Rev. 2024 Aug;211:115363. doi: 10.1016/j.addr.2024.115363. Epub 2024 Jun 19.
Adeno-associated virus (AAV) vectors have emerged as a promising tool in the development of gene therapies for various neurological diseases, including Alzheimer's disease and Parkinson's disease. However, the blood-brain barrier (BBB) poses a significant challenge to successfully delivering AAV vectors to the brain. Strategies that can overcome the BBB to improve the AAV delivery efficiency to the brain are essential to successful brain-targeted gene therapy. This review provides an overview of existing strategies employed for AAV delivery to the brain, including direct intraparenchymal injection, intra-cerebral spinal fluid injection, intranasal delivery, and intravenous injection of BBB-permeable AAVs. Focused ultrasound has emerged as a promising technology for the noninvasive and spatially targeted delivery of AAV administered by intravenous injection. This review also summarizes each strategy's current preclinical and clinical applications in treating neurological diseases. Moreover, this review includes a detailed discussion of the recent advances in the emerging focused ultrasound-mediated AAV delivery. Understanding the state-of-the-art of these gene delivery approaches is critical for future technology development to fulfill the great promise of AAV in neurological disease treatment.
腺相关病毒(AAV)载体已成为开发针对包括阿尔茨海默病和帕金森病在内的各种神经疾病的基因疗法的一种有前景的工具。然而,血脑屏障(BBB)对将AAV载体成功递送至大脑构成了重大挑战。能够克服血脑屏障以提高AAV向大脑递送效率的策略对于成功的脑靶向基因治疗至关重要。本综述概述了用于将AAV递送至大脑的现有策略,包括直接脑实质内注射、脑脊髓液注射、鼻内递送以及静脉注射可透过血脑屏障的AAV。聚焦超声已成为一种有前景的技术,可用于通过静脉注射进行AAV的无创和空间靶向递送。本综述还总结了每种策略在治疗神经疾病方面当前的临床前和临床应用。此外,本综述详细讨论了新兴的聚焦超声介导的AAV递送的最新进展。了解这些基因递送方法的最新技术对于未来技术发展以实现AAV在神经疾病治疗中的巨大潜力至关重要。
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