Analyzing an appropriate disease model system is important to conduct disease research. Analyzing cells obtained from patient tissues could not only help elucidate the pathological mechanisms and to develop novel therapy but also lead to personalized medicine in the future. However, it is generally difficult to collect and culture neuronal cells from patients suffering from neurodegenerative disorders. Skin fibroblasts are easier to collect than neurons but may not show the expected pathology when disease-relevant genes are not sufficiently expressed. In this article, I describe an in vitro model system that enables the facile analysis of neurological disease mechanisms in patient fibroblast cultures by CRISPR transcriptional activation of endogenous disease-relevant genes. This system introduces an additional platform to analyze neurodegenerative disorders.

分析合适的疾病模型系统对于进行疾病研究很重要。分析从患者组织中获得的细胞不仅有助于阐明病理机制和开发新疗法，还有助于未来的个性化医疗。然而，通常很难从患有神经退行性疾病的患者身上收集和培养神经元细胞。皮肤成纤维细胞比神经元更容易收集，但当疾病相关基因未充分表达时，可能不会表现出预期的病理。在这篇文章中，我描述了一个体外该模型系统能够通过内源性疾病相关基因的 CRISPR 转录激活轻松分析患者成纤维细胞培养物中的神经疾病机制。该系统引入了一个额外的平台来分析神经退行性疾病。