Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications

IF 15.2 1区医学 Q1 PHARMACOLOGY & PHARMACY Advanced drug delivery reviews Pub Date : 2024-06-19 DOI:10.1016/j.addr.2024.115363

Dezhuang Ye , Chinwendu Chukwu , Yaoheng Yang , Zhongtao Hu , Hong Chen

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Abstract

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.

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向大脑输送腺相关病毒载体：技术进步与临床应用。

腺相关病毒（AAV）载体已成为开发包括阿尔茨海默病和帕金森病在内的各种神经系统疾病基因疗法的一种前景广阔的工具。然而，血脑屏障（BBB）对成功将 AAV 载体送入大脑构成了巨大挑战。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开展脑靶向基因治疗至关重要。本综述概述了将 AAV 运送到大脑的现有策略，包括直接实质内注射、脑脊液内注射、鼻内注射和静脉注射 BBB 可渗透的 AAV。聚焦超声已成为通过静脉注射无创和空间靶向递送 AAV 的一种有前途的技术。本综述还总结了每种策略目前在治疗神经系统疾病方面的临床前和临床应用。此外，本综述还详细讨论了新兴的聚焦超声介导 AAV 递送技术的最新进展。了解这些基因递送方法的最新进展对于未来的技术开发至关重要，以实现 AAV 治疗神经系统疾病的巨大前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced drug delivery reviews 医学-药学

CiteScore

28.10

自引率

5.00%

发文量

294

审稿时长

15.1 weeks

期刊介绍： The aim of the Journal is to provide a forum for the critical analysis of advanced drug and gene delivery systems and their applications in human and veterinary medicine. The Journal has a broad scope, covering the key issues for effective drug and gene delivery, from administration to site-specific delivery. In general, the Journal publishes review articles in a Theme Issue format. Each Theme Issue provides a comprehensive and critical examination of current and emerging research on the design and development of advanced drug and gene delivery systems and their application to experimental and clinical therapeutics. The goal is to illustrate the pivotal role of a multidisciplinary approach to modern drug delivery, encompassing the application of sound biological and physicochemical principles to the engineering of drug delivery systems to meet the therapeutic need at hand. Importantly the Editorial Team of ADDR asks that the authors effectively window the extensive volume of literature, pick the important contributions and explain their importance, produce a forward looking identification of the challenges facing the field and produce a Conclusions section with expert recommendations to address the issues.