Department of Neurosurgery, Emory University, Atlanta, GA 30322, USA.
Hum Gene Ther. 2011 Sep;22(9):1129-35. doi: 10.1089/hum.2011.008. Epub 2011 Jul 25.
Gene therapy for motor neuron diseases requires efficient gene delivery to motor neurons (MNs) throughout the spinal cord and brainstem. The present study compared adeno-associated viral (AAV) vector serotypes 1, 6, 8, and 9 for spinal cord delivery in adult mice, by the intraparenchymal or intrathecal route of administration. Whereas intraparenchymal injections resulted in local transduction of the lumbar segment of the spinal cord, intrathecal injections led to a broader distribution, transducing cells along the sacral, lumbar, and lower thoracic spinal cord. Overall, AAV6 and AAV9 performed better than the other serotypes. Dramatic differences in cell-specific expression patterns could be observed when constructs bearing the chicken β-actin (Cba) versus cytomegalovirus (CMV) promoter were compared. In summary, intrathecal delivery of AAV6 or AAV9 vectors containing the CMV promoter yielded the strongest levels of biodistribution and MN transduction in the spinal cord.
用于运动神经元疾病的基因治疗需要将基因有效递送到脊髓和脑干中的运动神经元（MNs）。本研究通过脑实质内或鞘内给药途径比较了腺相关病毒（AAV）载体血清型 1、6、8 和 9 在成年小鼠脊髓中的传递情况。虽然脑实质内注射导致局部转导脊髓的腰段，但鞘内注射导致更广泛的分布，沿骶骨、腰椎和下胸椎脊髓转导细胞。总的来说，AAV6 和 AAV9 的表现优于其他血清型。当比较携带鸡β-肌动蛋白（Cba）与巨细胞病毒（CMV）启动子的构建体时，可以观察到细胞特异性表达模式的显著差异。总之，含有 CMV 启动子的 AAV6 或 AAV9 载体的鞘内递送在脊髓中产生了最强的生物分布和 MN 转导水平。
