Multidimensional chemical control of CRISPR-Cas9.
Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions-including dose, time, specificity, and mutually exclusive modulation of multiple genes-are still lacking. We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains. Application of our strategy to both Cas9-mediated genome editing and transcriptional activities opens new avenues for systematic genome interrogation.
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.|Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Basudeb
B
Maji
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Christopher L
CL
Moore
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Bernd
B
Zetsche
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Sara E
SE
Volz
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Feng
F
Zhang
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Matthew D
MD
Shoulders
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.|Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Amit
A
Choudhary
D064113:CRISPR-Cas Systems / Q000235:genetics*; D002478:Cells, Cultured; D000072669:Gene Editing / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D014157:Transcription Factors