鞘内注射 AAV9 可使猫整个中枢神经系统中的少突胶质细胞和运动神经元转导。
Intracisternal delivery of AAV9 results in oligodendrocyte and motor neuron transduction in the whole central nervous system of cats.
机构信息
Laboratoire de Thérapie Génique, INSERM UMR U1089, Institut de Recherche Thérapeutique 1, Université de Nantes, Nantes Cedex 01, France.
1] INRA UMR U703, Animal Pathophysiology and Biotherapy for Muscle and CNS Diseases, Nantes, France [2] Nantes-Atlantic College of Veterinary Medicine, Food Science and Engineering (Oniris), LUNAM University, Nantes Cedex 03, France.
出版信息
Gene Ther. 2014 May;21(5):522-8. doi: 10.1038/gt.2014.16. Epub 2014 Feb 27.
Systemic and intracerebrospinal fluid delivery of adeno-associated virus serotype 9 (AAV9) has been shown to achieve widespread gene delivery to the central nervous system (CNS). However, after systemic injection, the neurotropism of the vector has been reported to vary according to age at injection, with greater neuronal transduction in newborns and preferential glial cell tropism in adults. This difference has not yet been reported after cerebrospinal fluid (CSF) delivery. The present study analyzed both neuronal and glial cell transduction in the CNS of cats according to age of AAV9 CSF injection. In both newborns and young cats, administration of AAV9-GFP in the cisterna magna resulted in high levels of motor neurons (MNs) transduction from the cervical (84±5%) to the lumbar (99±1%) spinal cord, demonstrating that the remarkable tropism of AAV9 for MNs is not affected by age at CSF delivery. Surprisingly, numerous oligodendrocytes were also transduced in the brain and in the spinal cord white matter of young cats, but not of neonates, indicating that (i) age of CSF delivery influences the tropism of AAV9 for glial cells and (ii) AAV9 intracisternal delivery could be relevant for both the treatment of MN and demyelinating disorders.
腺相关病毒血清型 9(AAV9)的全身和脑脊髓液递送已被证明可实现中枢神经系统(CNS)的广泛基因传递。然而,在全身注射后,据报道,载体的神经亲嗜性根据注射时的年龄而变化,新生动物中神经元的转导更大,而成人则优先向神经胶质细胞亲嗜。这种差异在脑脊髓液(CSF)递送后尚未报道。本研究根据 AAV9 CSF 注射的年龄分析了猫中枢神经系统中的神经元和神经胶质细胞转导。在新生动物和幼猫中,向枕大池内给予 AAV9-GFP 导致颈段(84±5%)至腰段(99±1%)脊髓的运动神经元(MNs)转导水平较高,表明 AAV9 对 MNs 的显著亲嗜性不受 CSF 输送时年龄的影响。令人惊讶的是,年轻猫的大脑和脊髓白质中也转导了许多少突胶质细胞,但新生动物中没有,这表明(i)CSF 输送时的年龄影响 AAV9 对神经胶质细胞的亲嗜性,(ii)AAV9 鞘内递送可能与 MN 和脱髓鞘疾病的治疗都相关。