Deverman Benjamin E, Ravina Bernard M, Bankiewicz Krystof S, Paul Steven M, Sah Dinah W Y
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Stanley Center for Psychiatric Research at Broad Institute, Cambridge, MA, USA.
Nat Rev Drug Discov. 2018 Sep;17(9):641-659. doi: 10.1038/nrd.2018.110. Epub 2018 Aug 10.
Adeno-associated viral (AAV) vectors are a rapidly emerging gene therapy platform for the treatment of neurological diseases. In preclinical studies, transgenes encoding therapeutic proteins, microRNAs, antibodies or gene-editing machinery have been successfully delivered to the central nervous system with natural or engineered viral capsids via various routes of administration. Importantly, initial clinical studies have demonstrated encouraging safety and efficacy in diseases such as Parkinson disease and spinal muscular atrophy, as well as durability of transgene expression. Here, we discuss key considerations and challenges in the future design and development of therapeutic AAV vectors, highlighting the most promising targets and recent clinical advances.
腺相关病毒（AAV）载体是一种迅速兴起的用于治疗神经疾病的基因治疗平台。在临床前研究中，编码治疗性蛋白质、微小RNA、抗体或基因编辑机制的转基因已通过各种给药途径，利用天然或工程化病毒衣壳成功递送至中枢神经系统。重要的是，初步临床研究已在帕金森病和脊髓性肌萎缩症等疾病中显示出令人鼓舞的安全性和有效性，以及转基因表达的持久性。在此，我们讨论治疗性AAV载体未来设计和开发中的关键考虑因素与挑战，重点介绍最有前景的靶点和近期临床进展。
