TY - JOUR
T1 - Allosteric regulation of CRISPR-Cas9 for DNA-targeting and cleavage
AU - Zuo, Zhicheng
AU - Liu, Jin
N1 - Funding Information:
This work was supported by Shanghai Municipal Education Commission under the program for Professor of Special Appointment at Shanghai Institutions of Higher Learning to Z. Z.; National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R15HL147265 to J.L. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
This work was supported by Shanghai Municipal Education Commission under the program for Professor of Special Appointment at Shanghai Institutions of Higher Learning to Z. Z.; National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R15HL147265 to J.L. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/6
Y1 - 2020/6
N2 - The CRISPR-Cas9 system from Streptococcus pyogenes has been exploited as a programmable RNA-guided DNA-targeting and DNA-editing platform. This evolutionary tool enables diverse genetic manipulations with unprecedented precision and ease. Cas9 is an allosteric enzyme, which is allosterically regulated in conformational activation, target recognition, and DNA cleavage. Here, we outline the underlying allosteric control over the Cas9 complex assembly and targeting specificity. We further review the strategies for mitigating intrinsic Cas9 off-target effects through allosteric modulations and the advances in engineering controllable Cas9 systems that are responsive to external allosteric signals. Future development of highly specific, tunable CRISPR-Cas9 systems through allosteric modulations would greatly benefit applications that require both conditional control and high precision.
AB - The CRISPR-Cas9 system from Streptococcus pyogenes has been exploited as a programmable RNA-guided DNA-targeting and DNA-editing platform. This evolutionary tool enables diverse genetic manipulations with unprecedented precision and ease. Cas9 is an allosteric enzyme, which is allosterically regulated in conformational activation, target recognition, and DNA cleavage. Here, we outline the underlying allosteric control over the Cas9 complex assembly and targeting specificity. We further review the strategies for mitigating intrinsic Cas9 off-target effects through allosteric modulations and the advances in engineering controllable Cas9 systems that are responsive to external allosteric signals. Future development of highly specific, tunable CRISPR-Cas9 systems through allosteric modulations would greatly benefit applications that require both conditional control and high precision.
UR - http://www.scopus.com/inward/record.url?scp=85079394085&partnerID=8YFLogxK
U2 - 10.1016/j.sbi.2020.01.013
DO - 10.1016/j.sbi.2020.01.013
M3 - Review article
C2 - 32070859
AN - SCOPUS:85079394085
SN - 0959-440X
VL - 62
SP - 166
EP - 174
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
ER -