Read ministration of adenoviral gene delivery to dopamine neurons
Read ministration of adenoviral gene delivery to dopamine neurons
复制标题
DOI：
10.1097/wnr.0b013e3282f03fe5
复制
发表时间：
2007-10-08
期刊：
影响因子：
1.7
通讯作者：
Wood, Matthew J. A.
中科院分区：
文献类型：
--
作者：
Gonzalez, Sarah C.;McMenamin, Margaret M.;Wood, Matthew J. A.
目前正在探索的一种治疗帕金森氏症的方法是基因疗法。一个重要的问题涉及转基因在多巴胺神经元中表达的持续时间，以及载体的持久性、神经元损伤和将载体重新管理到同一神经元群体的可行性。我们发现，使用表达LacZ报告基因的腺病毒载体，转基因表达随着时间的推移而下降，但多巴胺神经元或载体DNA的损失最小。载体的重新给药导致低水平的转基因输送到神经元。此外，载体已经被输送到的神经元无法运输逆行示踪剂荧光金。我们的发现表明，尽管病毒持续存在，但转基因表达在多巴胺神经元中下降，并且将载体重新输送到这些神经元的能力是有限的。
An approach currently being explored as treatment for Parkinson's disease is gene therapy. An important question concerns the duration of transgene expression in dopamine neurons and the issues of vector persistence, neuronal damage and the feasibility of readministering vector to the same neuronal population. We show, using an adenoviral vector expressing the LacZ reporter gene, that transgene expression declined over time but with minimal loss of dopamine neurons or vector DNA. Readministration of vector resulted in low levels of transgene delivery to the neurons. Moreover, the neurons to which vector had already been delivered were unable to transport the retrograde tracer fluorogold. Our findings indicate that transgene expression declined in dopamine neurons despite the persistence of virus, and the capacity to readminister vector to these neurons was limited.