Small molecule-triggered Cas9 protein with improved genome-editing specificity

被引：0

作者：

Davis, Kevin M. ^{[1
,2
]}

Pattanayak, Vikram ^{[3
]}

Thompson, David B. ^{[1
,2
]}

Zuris, John A. ^{[1
,2
]}

Liu, David R. ^{[1
,2
]}

机构：

[1] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[2] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA

[3] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

来源：

NATURE CHEMICAL BIOLOGY | 2015年 / 11卷 / 05期

基金：

加拿大自然科学与工程研究理事会; 美国国家卫生研究院;

关键词：

HUMAN-CELLS; NUCLEASE SPECIFICITY; DIRECTED EVOLUTION; MAMMALIAN-CELLS; RNA; NICKASES; CLEAVAGE; DELIVERY; INTEIN;

D O I：

10.1038/NCHEMBIO.1793

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen-responsive intein at specific positions in Cas9. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9.

引用

页码：316 / U97

页数：4

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