Kampmann Martin
Institute for Neurodegenerative Diseases, Department of Biochemistry and Biophysics, University of California, San Francisco and Chan Zuckerberg Biohub, San Francisco, California, USA.
Chem Commun (Camb). 2017 Jun 29;53(53):7162-7167. doi: 10.1039/c7cc02349a.
Phenotypic screening is a powerful approach to discover small molecules with desired effects on biological systems, which can then be developed into therapeutic drugs. The identification of the target and mechanism of action of compounds discovered in phenotypic screens remains a major challenge. This feature article describes the use of genetic tools to reveal drug targets and mechanisms in mammalian cells. Until recently, RNA interference was the method of choice for such studies. Here, we highlight very recent additions to the genetic toolkit in mammalian cells, including CRISPR, CRISPR interference, and CRISPR activation, and illustrate their usefulness for drug target identification.
表型筛选是一种发现对生物系统具有预期作用的小分子的有效方法，这些小分子随后可被开发成治疗药物。确定在表型筛选中发现的化合物的靶点和作用机制仍然是一项重大挑战。这篇专题文章描述了利用遗传工具来揭示哺乳动物细胞中的药物靶点和作用机制。直到最近，RNA干扰一直是此类研究的首选方法。在这里，我们重点介绍哺乳动物细胞遗传工具包中最新增加的工具，包括CRISPR、CRISPR干扰和CRISPR激活，并举例说明它们在药物靶点识别方面的用途。
