Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria; Medical University of Vienna, Vienna BioCenter (VBC), 1030 Vienna, Austria.
Curr Opin Genet Dev. 2019 Feb;54:41-47. doi: 10.1016/j.gde.2019.03.003. Epub 2019 Apr 2.
Drug development remains a slow and expensive process, while the effective use of established therapeutics is widely hampered by our limited understanding of response and resistance mechanisms. Functional-genetic tools such as CRISPR/Cas9, advanced RNAi methods, and targeted protein degradation, together with other emerging technologies such as time-resolved and single-cell transcriptomics, fundamentally change the way we can search for candidate therapeutic targets and evaluate them before drug development. In addition, for already available therapeutics these tools open vast opportunities for probing response mechanisms and predictive biomarkers, and thereby guide the development of personalized therapies. Here, we review promising applications and remaining limitations of recently established functional-genetic tools for high-throughput screening and the in-depth analysis of candidate targets and established drugs.
药物研发仍然是一个缓慢而昂贵的过程，而既定治疗方法的有效利用也受到我们对反应和耐药机制的有限理解的广泛阻碍。功能基因组学工具，如 CRISPR/Cas9、先进的 RNAi 方法和靶向蛋白降解，以及其他新兴技术，如时间分辨和单细胞转录组学，从根本上改变了我们寻找候选治疗靶点并在药物研发之前对其进行评估的方式。此外，对于已经可用的治疗方法，这些工具为探索反应机制和预测性生物标志物提供了广阔的机会，并由此指导个性化治疗的发展。在这里，我们回顾了最近建立的功能基因组学工具在高通量筛选以及候选靶点和既定药物的深入分析方面的有前途的应用和仍然存在的局限性。
