A Non-Viral Vector for Targeting Gene Therapy to Motoneurons in the CNS
A Non-Viral Vector for Targeting Gene Therapy to Motoneurons in the CNS
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DOI：
10.1159/000080050
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发表时间：
2004-01-01
影响因子：
3
通讯作者：
Osta, Rosario
中科院分区：
文献类型：
--
作者：
Miana-Mena, Francisco J.;Munoz, Maria J.;Osta, Rosario
在神经退行性疾病领域，需要靶向运动神经元细胞的基因治疗载体。我们建议使用破伤风毒素(TTC)的无毒片段C作为运动神经元的生物活性载体。用编码β-半乳糖苷酶-TTC杂化蛋白的裸DNA在体内转染肌细胞，使酶活性选择性地转移到中枢神经系统。在肌肉中，β-半乳糖苷酶的表达在注射后24小时即可检测到，在注射后4天达到最大值，此后逐渐下降。注射后4d开始观察舌下运动神经元和运动皮质的标记。在本文中，我们证明了当肌肉细胞在体内被转基因时，TTC作为一种酶活性载体作用于中枢神经系统。我们还表明，TTC的存在对转基因基因的表达没有任何影响。这两个结果都值得进一步研究TTC作为基因治疗领域中治疗运动神经元疾病的手段。版权所有(C)2004 S.Karger AG，巴塞尔
Gene therapy vectors that can be targeted to motoneuronal cells are required in the field of neurodegenerative diseases. We propose the use of the atoxic fragment C of tetanus toxin (TTC) as biological activity carrier to the motoneurons. Naked DNA encoding beta-galactosidase-TTC hybrid protein was used to transfect muscle cells in vivo, resulting in a selective gene transfer of the enzymatic activity to the CNS. In the muscle, level expression of beta-galactosidase was readily detectable 24 h after injection, reaching a maximum after 4 days and gradually decreasing thereafter. Labelling in the hypoglossal motoneurons and motor cortex was observed from 4 days after injection. In this paper, we show that TTC works as an enzymatic activity carrier to the CNS when muscle cells are transfected in vivo. We have also shown that the presence of TTC does not have any influence on the expression of the transfected gene. Both these results warrant further studies of TTC as a means of treating motoneuron diseases in the field of gene therapy. Copyright (C) 2004 S. Karger AG, Basel