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Generation and genetic modification of induced pluripotent stem cells.

机译:诱导多能干细胞的产生和遗传修饰。

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IMPORTANCE OF THE FIELD: The generation of induced pluripotent stem cells (iPSCs) enabled by exogenous expression of the canonical Oct4, Sox2, Klf4 and c-Myc reprogramming factors has opened new ways to create patient- or disease-specific pluripotent cells. iPSCs represent an almost inexhaustible source of cells for targeted differentiation into somatic effector cells and hence are likely to be invaluable for therapeutic applications and disease-related research. AREAS COVERED IN THIS REVIEW: After an introduction on the biology of reprogramming we cover emerging technological advances, including new reprogramming approaches, small-molecule compounds and tailored genetic modification, and give an outlook towards potential clinical applications of iPSCs. WHAT THE READER WILL GAIN: Although this field is progressing rapidly, reprogramming is still an inefficient process. The reader will learn about innovative tools to generate patient-specific iPSCs and how to modify these established lines in a safe way. Ideally, the disease-causing mutation is edited directly in the genome using novel technologies based on artificial nucleases, such as zinc-finger nucleases. TAKE HOME MESSAGE: Human iPSCs create fascinating options with regard to disease modeling, drug testing, developmental studies and therapeutic applications. However, important hurdles have to be taken and more efficient protocols to be established to achieve the ambitious goal of bringing iPSCs into clinical use.
机译:领域的重要性:通过规范性Oct4,Sox2,Klf4和c-Myc重编程因子的外源表达,诱导多能干细胞(iPSC)的产生为创建患者或疾病特异性多能细胞开辟了新途径。 iPSC代表了几乎无穷无尽的细胞,可定向分化为体细胞效应细胞,因此对于治疗应用和疾病相关研究可能具有不可估量的价值。这篇综述涵盖的领域:在介绍了重编程生物学之后,我们介绍了新兴的技术进步,包括新的重编程方法,小分子化合物和量身定制的基因修饰,并展望了iPSC的潜在临床应用。读者的收获:尽管该领域正在迅速发展,但是重新编程仍然是一个低效的过程。读者将学习有关生成特定于患者的iPSC的创新工具,以及如何以安全的方式修改这些既定系。理想情况下,使用基于人工核酸酶(例如锌指核酸酶)的新技术在基因组中直接编辑引起疾病的突变。寄语:人类iPSC在疾病建模,药物测试,发育研究和治疗应用方面创造了引人入胜的选择。然而,要实现将iPSC投入临床使用的宏伟目标,就必须采取重要的障碍并建立更有效的协议。

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