Towards a toolbox for mammalian gene editing: Removing off-target activity and protein interactions of Cas9

打造哺乳动物基因编辑工具箱：消除 Cas9 的脱靶活性和蛋白质相互作用

• 批准号: RGPIN-2016-06381
• 负责人: Hubbard, Basil
• 金额: $ 3.13万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629923
• 关键词: Towards; toolbox; mammalian; gene; editing

In the past 30 years, molecular genetics research has resulted in unprecedented breakthroughs in sequencing and annotating the mammalian genome. One of the main challenges now facing researchers is how to efficiently assign function to each gene. While researchers typically analyze phenotypic changes associated with gene loss-of-function, classical techniques for performing gene knockout in mammalian organisms are slow, laborious, and costly. Recently, DNA sequence-specific nucleases (SSNs) such as TALENs and CRISPR/Cas9 have emerged as tools that are poised to revolutionize this process. An over-arching goal of my lab is to develop robust technology for genetically altering mammalian organisms with high precision. Through a combination of molecular evolution and proteomics approaches, this program will develop a gene editing toolbox for mammals that will realize this possibility.

在过去的30年里，分子遗传学研究在哺乳动物基因组测序和注释方面取得了前所未有的突破。研究人员现在面临的主要挑战之一是如何有效地为每个基因分配功能。虽然研究人员通常分析与基因功能丧失相关的表型变化，但在哺乳动物生物体中进行基因敲除的经典技术缓慢、费力且昂贵。最近，TALEN 和 CRISPR/Cas9 等 DNA 序列特异性核酸酶 (SSN) 已成为有望彻底改变这一过程的工具。我实验室的首要目标是开发强大的技术来高精度地改变哺乳动物的基因。通过分子进化和蛋白质组学方法的结合，该计划将为哺乳动物开发一个基因编辑工具箱，以实现这种可能性。