Chemical and optical control of CRISPR-associated nucleases

Ashley E Modell; Sachini U Siriwardena; Veronika M Shoba; Xing Li; Amit Choudhary

doi:10.1016/j.cbpa.2020.10.003

Chemical and optical control of CRISPR-associated nucleases

Curr Opin Chem Biol. 2021 Feb:60:113-121. doi: 10.1016/j.cbpa.2020.10.003. Epub 2020 Nov 27.

Authors

Ashley E Modell¹, Sachini U Siriwardena¹, Veronika M Shoba¹, Xing Li¹, Amit Choudhary²

Affiliations

¹ Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
² Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA; Divisions of Renal Medicine and Engineering, Brigham and Women's Hospital, Boston, MA, 02115, USA. Electronic address: achoudhary@bwh.harvard.edu.

PMID: 33253976
DOI: 10.1016/j.cbpa.2020.10.003

Abstract

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system of bacteria has furnished programmable nucleases (e.g., Cas9) that are transforming the field of genome editing with applications in basic and biomedical research, biotechnology, and agriculture. However, broader real-world applications of Cas9 require precision control of its activity over dose, time, and space as off-target effects, embryonic mosaicism, chromosomal translocations, and genotoxicity have been observed with elevated and/or prolonged nuclease activity. Here, we review chemical and optical methods for precision control of Cas9's activity.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

CRISPR-Associated Protein 9 / chemistry*
CRISPR-Associated Protein 9 / metabolism*
Gene Editing
Humans
Optical Phenomena*

Substances

CRISPR-Associated Protein 9

Grants and funding

R01 GM132825/GM/NIGMS NIH HHS/United States