Cornerstones of CRISPR-Cas in drug discovery and therapy.
Cornerstones of CRISPR-Cas in drug discovery and therapy.
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DOI：
10.1038/nrd.2016.238
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Corn JE
中科院分区：
文献类型：
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作者：
Fellmann C;Gowen BG;Lin PC;Doudna JA;Corn JE
CRISPR-Cas系统作为易于获取和可编程的基因组编辑和调控工具，最近的发展正在推动生物学的一场革命。随着个性化和参考基因组序列信息的快速扩展，基于CRISPR-Cas的技术使几乎无限的基因操作成为可能，甚至在以前困难的环境中，包括人类细胞。尽管很多注意力都集中在CRISPR-Cas治疗孟德尔疾病的潜力上，但这项技术也有希望改变治疗复杂遗传性和躯体疾病的疗法的发展。在这里，我们讨论了CRISPR-Cas如何通过加速高价值靶点的识别和验证，发现高可信度的生物标志物和开发差异化的突破性疗法来影响下一代药物。我们专注于这项革命性基因编辑技术的前景、陷阱和障碍，并讨论了不同CRISPR-Cas筛选平台的关键方面，并提供了我们对基因组工程最佳实践的看法。
The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing and regulation is spurring a revolution in biology. Paired with the rapid expansion of personalized and reference genomic sequence information, technologies based on CRISPR-Cas are enabling nearly unlimited genetic manipulation even in previously difficult contexts, including human cells. Although much attention has focused on the potential of CRISPR-Cas to cure Mendelian diseases, the technology also holds promise to transform the development of therapies to treat complex heritable and somatic disorders. Here we discuss how CRISPR-Cas can impact the next generation of drugs through accelerating the identification and validation of high-value targets, uncovering high confidence biomarkers and developing differentiated breakthrough therapies. We focus on the promises, pitfalls and hurdles of this revolutionary gene editing technology, and also discuss key aspects of different CRISPR-Cas screening platforms and offer our perspectives on the best practices in genome engineering.