Optogenetic Approaches to Drug Discovery in Neuroscience and Beyond.
Optogenetic Approaches to Drug Discovery in Neuroscience and Beyond.
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DOI：
10.1016/j.tibtech.2017.04.002
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发表时间：
2017-07
影响因子：
17.3
通讯作者：
Cohen AE
中科院分区：
文献类型：
--
作者：
Zhang H;Cohen AE
光遗传学的最新进展为药物发现开辟了新的途径，特别是在神经科学领域。生理细胞分析探测将基因组数据与患者健康联系起来的功能表型。光遗传学工具，特别是用于全光学电生理学的工具，现在提供了以前所未有的通量和信息内容探测细胞疾病模型的手段。这些技术有望鉴定与疾病状态相关的功能表型，并鉴定改善细胞功能的化合物，无论化合物是直接作用于靶标还是通过旁路机制。这篇综述讨论了在整个发现管道中应用光遗传学技术的机会和未解决的挑战，从目标识别和验证，到基于目标的和表型筛选，再到临床试验。
Recent advances in optogenetics have opened new routes to drug discovery, particularly in neuroscience. Physiological cellular assays probe functional phenotypes that connect genomic data to patient health. Optogenetic tools, and in particular tools for all-optical electrophysiology, now provide means to probe cellular disease models with unprecedented throughput and information content. These techniques promise to identify functional phenotypes associated with disease states and to identify compounds that improve cellular function regardless of whether the compound acts directly on a target or through a bypass mechanism. This review discusses opportunities and unresolved challenges in applying optogenetic techniques throughout the discovery pipeline, from target identification and validation, to target-based and phenotypic screens, to clinical trials.