a Department of Neurosurgery , Emory University , Atlanta , GA , USA.
Expert Opin Biol Ther. 2018 Mar;18(3):293-307. doi: 10.1080/14712598.2018.1416089. Epub 2017 Dec 18.
Adeno-associated viral (AAV) vector-mediated gene delivery to the spinal cord has finally entered the pathway towards regulatory approval. Phase 1 clinical trials using AAV gene therapy for pediatric disorders - spinal muscular atrophy (SMA) and giant axonal neuropathy (GAN) - are now underway.
This review addresses the latest progress in the field of AAV gene delivery to the spinal cord, particularly focusing on the most prominent AAV serotypes and delivery methodologies to the spinal cord. Candidate diseases and scaling up experiments in large animals are also discussed.
Intravenous (IV) and intrathecal (IT) deliveries seem to undoubtedly be the preferred routes of administration for diffuse spinal cord delivery of therapeutic AAV vectors that can cross the blood-brain barrier (BBB) and correct inherited genetic disorders. Conversely, intraparenchymal delivery is still an undervalued but very viable approach for segmental therapy in afflictions such as ALS or Pompe Disease as a means to prevent respiratory dysfunction.
腺相关病毒（AAV）载体介导的脊髓基因传递终于进入了监管批准的途径。目前正在进行使用 AAV 基因治疗儿科疾病——脊髓性肌萎缩症（SMA）和巨大轴突神经病（GAN）——的 1 期临床试验。
本综述讨论了 AAV 基因传递到脊髓领域的最新进展，特别是侧重于最突出的 AAV 血清型和脊髓传递方法。候选疾病和在大型动物中的扩大实验也进行了讨论。
静脉内（IV）和鞘内（IT）给药似乎无疑是治疗性 AAV 载体弥散性脊髓传递的首选给药途径，这些载体可以穿过血脑屏障（BBB）并纠正遗传性遗传疾病。相反，脑实质内给药仍然是一种被低估但非常可行的方法，用于 ALS 或 Pompe 病等疾病的节段性治疗，作为预防呼吸功能障碍的一种手段。
