Controlling and enhancing CRISPR systems

Haridha Shivram; Brady F Cress; Gavin J Knott; Jennifer A Doudna

doi:10.1038/s41589-020-00700-7

Controlling and enhancing CRISPR systems

Nat Chem Biol. 2021 Jan;17(1):10-19. doi: 10.1038/s41589-020-00700-7. Epub 2020 Dec 16.

Authors

Haridha Shivram^{1

2}, Brady F Cress^{1

2}, Gavin J Knott^{1

2

3}, Jennifer A Doudna^{4

5

6

7

8

9

10}

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
² Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
³ Monash Biomedicine Discovery Institute, Department of Biochemistry & Molecular Biology, Monash University, Victoria, Australia.
⁴ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. [email protected].
⁵ Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. [email protected].
⁶ Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA. [email protected].
⁷ California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA. [email protected].
⁸ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA. [email protected].
⁹ MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, Berkeley, CA, USA. [email protected].
¹⁰ Gladstone Institutes, University of California, San Francisco, San Francisco, CA, USA. [email protected].

Abstract

Many bacterial and archaeal organisms use clustered regularly interspaced short palindromic repeats-CRISPR associated (CRISPR-Cas) systems to defend themselves from mobile genetic elements. These CRISPR-Cas systems are classified into six types based on their composition and mechanism. CRISPR-Cas enzymes are widely used for genome editing and offer immense therapeutic opportunity to treat genetic diseases. To realize their full potential, it is important to control the timing, duration, efficiency and specificity of CRISPR-Cas enzyme activities. In this Review we discuss the mechanisms of natural CRISPR-Cas regulatory biomolecules and engineering strategies that enhance or inhibit CRISPR-Cas immunity by altering enzyme function. We also discuss the potential applications of these CRISPR regulators and highlight unanswered questions about their evolution and purpose in nature.

Publication types

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

MeSH terms

Antibiosis / genetics
Archaea / genetics*
Archaea / metabolism
Archaea / virology
Bacteria / genetics*
Bacteria / metabolism
Bacteria / virology
Bacteriophages / genetics
Bacteriophages / growth & development
Bacteriophages / metabolism
CRISPR-Associated Protein 9 / genetics
CRISPR-Associated Protein 9 / metabolism
CRISPR-Cas Systems*
Clustered Regularly Interspaced Short Palindromic Repeats*
Gene Editing / methods
Gene Expression Regulation, Archaeal*
Gene Expression Regulation, Bacterial*
Genetic Engineering / methods
Humans
Interspersed Repetitive Sequences
RNA, Guide, CRISPR-Cas Systems / genetics
RNA, Guide, CRISPR-Cas Systems / metabolism

Substances

RNA, Guide, CRISPR-Cas Systems
CRISPR-Associated Protein 9

Abstract

Publication types

MeSH terms

Substances

Grants and funding