Croci C, Fasano S, Superchi D, Perani L, Martellosio A, Brambilla R, Consalez G, Bongarzone E R
San Raffaele Telethon Institute for Gene Therapy, Milan, Italy.
Dev Neurosci. 2006;28(3):216-21. doi: 10.1159/000091919.
Due to the profuse connections of the cerebellum to the rest of the central nervous system, cerebellar dysfunction impacts tremendously on movement coordination, maintenance of equilibrium, muscle tone and motor memory. Efficient gene transfer of therapeutic genes to this central nervous system structure would constitute a relevant step ahead the design of treatments to ameliorate cerebellar dysfunction. Lentiviral vectors (LVs) have been used as efficient vehicles to integrate transgenes into dividing and non-dividing cells, such as postmitotic adult neurons, with minimal toxicity and immune response. This study aimed to use LVs carrying green fluorescent protein (GFP) cDNA for transduction of cerebellar cells in vivo without compromising neurological cerebellar functions. Our results indicate that LVs, injected in the lobulus simplex, transduced different cerebellar neurons including stellate, Purkinje cells, granular neurons and glial cells such as astrocytes, oligodendrocytes, and that this gene transfer approach was not accompanied by cerebellar deficits.
由于小脑与中枢神经系统其他部分存在广泛的联系，小脑功能障碍对运动协调、平衡维持、肌张力和运动记忆有极大影响。将治疗性基因高效导入这个中枢神经系统结构，将是设计改善小脑功能障碍治疗方法的一个重要进展。慢病毒载体（LVs）已被用作有效的载体，可将转基因整合到分裂和非分裂细胞中，如成熟的有丝分裂后神经元，且毒性和免疫反应最小。本研究旨在使用携带绿色荧光蛋白（GFP）cDNA的慢病毒载体在不损害小脑神经功能的情况下体内转导小脑细胞。我们的结果表明，注射到单小叶的慢病毒载体转导了不同的小脑神经元，包括星状细胞、浦肯野细胞、颗粒神经元以及胶质细胞，如星形胶质细胞、少突胶质细胞，并且这种基因转移方法并未伴随小脑功能缺陷。
