The motor system controls muscle movement through lower motor neurons in the spinal cord and brainstem. Lower motor neurons are efferent neurons in the central nervous system (CNS) characterized by axonal projections that reach specific targets in the periphery. Lower motor neuron lesions result in the denervation and dysfunction of peripheral skeletal muscle. Great progress has been made to develop therapeutic strategies to transduce lower motor neurons with genes. However, the widespread distribution of lower motor neurons makes their specific, extensive, and efficient transduction a challenge. In this study, we demonstrated that, compared to the other tested recombinant adeno-associated virus (rAAV) serotypes, rAAV2-retro mediated the most efficient retrograde transduction of lower motor neurons in the spinal cord following intramuscular injection in neonatal mice. A single injection of rAAV2-retro in a single muscle enabled the efficient and extensive transduction of lower motor neurons in the spinal cord and brainstem rather than transducing only the lower motor neurons connected to the injected muscle. rAAV2-retro achieved the extensive transduction of lower motor neurons by the cerebrospinal fluid pathway. Our work suggests that gene delivery via the intramuscular injection of rAAV2-retro represents a promising tool in the development of gene therapy strategies for motor neuron diseases.

中文翻译：

---

rAAV2-Retro能够在肌肉内注射后广泛有效地传导下运动神经元。

运动系统控制脊髓和脑干中下部运动神经元的肌肉运动。下运动神经元是中枢神经系统（CNS）中的传出神经元，其特征是轴突投射到达周围的特定目标。下运动神经元病变导致周围骨骼肌的神经支配和功能障碍。在开发用基因转导下运动神经元的治疗策略方面已经取得了重大进展。然而，下运动神经元的广泛分布使其特异性，广泛和有效的转导成为挑战。在这项研究中，我们证明了与其他经过测试的重组腺相关病毒（rAAV）血清型相比，在新生小鼠肌肉内注射后，rAAV2-retro介导了脊髓中下运动神经元的最有效逆行转导。在单个肌肉中单次注射rAAV2-retro可以有效且广泛地转导脊髓和脑干中的下运动神经元，而不是仅转导与所注射肌肉相连的下运动神经元。rAAV2-retro通过脑脊髓液途径实现了下运动神经元的广泛转导。我们的工作表明，通过肌肉内注射rAAV2-retro进行基因递送代表了运动神经元疾病基因治疗策略发展中的有前途的工具。在单个肌肉中单次注射rAAV2-retro可以有效且广泛地转导脊髓和脑干中的下运动神经元，而不是仅转导与所注射肌肉相连的下运动神经元。rAAV2-retro通过脑脊髓液途径实现了下运动神经元的广泛转导。我们的工作表明，通过肌肉内注射rAAV2-retro进行基因递送代表了运动神经元疾病基因治疗策略发展中的有前途的工具。在单个肌肉中单次注射rAAV2-retro可以有效且广泛地转导脊髓和脑干中的下运动神经元，而不是仅转导与所注射肌肉相连的下运动神经元。rAAV2-retro通过脑脊髓液途径实现了下运动神经元的广泛转导。我们的工作表明，通过肌肉内注射rAAV2-retro进行基因递送代表了运动神经元疾病基因治疗策略发展中的有前途的工具。