Neve R L, Geller A I
Harvard Medical School, MA, USA.
Clin Neurosci. 1995;3(5):262-7.
The delivery of exogenous genes into the brain is becoming an increasingly important strategy for answering questions about the molecular mechanisms of brain function. Answers to these questions may be applied to many of the disorders that affect the brain. For example, a detailed understanding of the mechanisms that modulate long-term changes in neurotransmitter release will almost certainly lead to new approaches to diseases such as the epilepsies, in which neurotransmitter release is altered. Knowledge of the molecular means by which neurotransmitters shape neuronal development and cause neurodegeneration, or how trophic factors regulate neuronal health, will lead to insights into how defects in these pathways cause specific diseases. To answer these questions, we have developed a defective herpes simplex virus (HSV) system for the delivery of exogenous genes into the brain. This system directs precise spatial and temporal expression of recombinant genes in the brain. We discuss its utility in comparison to other methods of gene transfer into the brain for answering basic questions about the molecular basis for neuronal physiology and for gene therapy.
将外源基因导入大脑正日益成为一种重要策略，用于解答有关脑功能分子机制的问题。这些问题的答案可能适用于许多影响大脑的疾病。例如，深入了解调节神经递质释放长期变化的机制几乎肯定会带来针对癫痫等疾病的新方法，在癫痫中神经递质释放会发生改变。了解神经递质塑造神经元发育、导致神经退行性变的分子方式，或者神经营养因子如何调节神经元健康，将有助于深入了解这些途径中的缺陷如何导致特定疾病。为了回答这些问题，我们开发了一种缺陷型单纯疱疹病毒（HSV）系统，用于将外源基因导入大脑。该系统可在大脑中指导重组基因进行精确的空间和时间表达。我们将其与其他将基因导入大脑的方法进行比较，讨论其在解答有关神经元生理学分子基础的基本问题以及基因治疗方面的效用。
