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）载体是用于治疗神经系统疾病的快速兴起的基因治疗平台。在临床前研究中，编码治疗性蛋白质，microRNA，抗体或基因编辑机制的转基因已通过各种给药途径成功地与天然或工程化的病毒衣壳一起传递至中枢神经系统。重要的是，初步的临床研究表明，在诸如帕金森氏病和脊髓性肌萎缩症等疾病中，令人鼓舞的安全性和有效性以及转基因表达的持久性。在这里，我们讨论治疗性AAV载体的未来设计和开发中的主要考虑因素和挑战，重点介绍了最有希望的靶标和最新的临床进展。