Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
Curr Opin Chem Biol. 2024 Dec;83:102532. doi: 10.1016/j.cbpa.2024.102532. Epub 2024 Sep 28.
Harnessing adeno-associated virus (AAV) vectors for therapeutic gene delivery has emerged as a progressively promising strategy to treat disorders of both the central nervous system (CNS) and peripheral nervous system (PNS), and there are many ongoing clinical trials. However, unique physiological and molecular characteristics of the CNS and PNS pose obstacles to efficient vector delivery, ranging from the blood-brain barrier to the diverse nature of nervous system disorders. Engineering novel AAV capsids may help overcome these ongoing challenges and maximize therapeutic transgene delivery. This article discusses strategies for innovative AAV capsid development, highlighting recent advances. Notably, advances in next generation sequencing and machine learning have sparked new approaches for capsid investigation and engineering. Furthermore, we outline future directions and additional challenges in AAV-mediated gene therapy in the CNS and PNS.
腺相关病毒 (AAV) 载体被用于治疗基因传递，已成为治疗中枢神经系统 (CNS) 和周围神经系统 (PNS) 疾病的一种极具前景的策略，目前有许多正在进行的临床试验。然而，CNS 和 PNS 的独特生理和分子特性给有效的载体传递带来了障碍，从血脑屏障到神经系统疾病的多样性。工程新型 AAV 衣壳可能有助于克服这些持续存在的挑战，并最大限度地提高治疗性转基因的传递。本文讨论了创新的 AAV 衣壳开发策略，重点介绍了最新进展。值得注意的是，下一代测序和机器学习的进步为衣壳的研究和工程提供了新的方法。此外，我们还概述了 CNS 和 PNS 中 AAV 介导的基因治疗的未来方向和额外挑战。
