Anti-CRISPR proteins targeting the CRISPR-Cas system enrich the toolkit for genetic engineering

FEBS J. 2020 Feb;287(4):626-644. doi: 10.1111/febs.15139. Epub 2019 Nov 29.

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas adaptive immune defense systems, which are widely distributed in bacteria and Archaea, can provide sequence-specific protection against foreign DNA or RNA in some cases. However, the evolution of defense systems in bacterial hosts did not lead to the elimination of phages, and some phages carry anti-CRISPR genes that encode products that bind to the components mediating the defense mechanism and thus antagonize CRISPR-Cas immune systems of bacteria. Given the extensive application of CRISPR-Cas9 technologies in gene editing, in this review, we focus on the anti-CRISPR proteins (Acrs) that inhibit CRISPR-Cas systems for gene editing. We describe the discovery of Acrs in immune systems involving type I, II, and V CRISPR-Cas immunity, discuss the potential function of Acrs in inactivating type II and V CRISPR-Cas systems for gene editing and gene modulation, and provide an outlook on the development of important biotechnology tools for genetic engineering using Acrs.

Keywords: CRISPR-Cas; Cas9; anti-CRISPR proteins; phage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Archaea / genetics*
  • Archaea / immunology
  • Archaea / virology
  • Bacteria / genetics*
  • Bacteria / immunology
  • Bacteria / virology
  • Bacteriophages / genetics
  • Bacteriophages / metabolism
  • CRISPR-Associated Protein 9 / genetics
  • CRISPR-Associated Protein 9 / metabolism
  • CRISPR-Cas Systems*
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Evolution, Molecular
  • Gene Editing / methods*
  • Genetic Engineering / methods*
  • Humans
  • RNA, Guide, CRISPR-Cas Systems / genetics
  • RNA, Guide, CRISPR-Cas Systems / immunology
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • RNA, Guide, CRISPR-Cas Systems
  • Repressor Proteins
  • Viral Proteins
  • CRISPR-Associated Protein 9

Associated data

  • GENBANK/WP_049360089.1
  • GENBANK/WP_042743678.1
  • GENBANK/WP_042743676.1
  • GENBANK/WP_049372635.1
  • GENBANK/WP_002642161.1
  • GENBANK/WP_003722518.1
  • GENBANK/WP_014930691
  • GENBANK/WP_003723290.1
  • GENBANK/D4276_028
  • GENBANK/D1811_026
  • GENBANK/VDB32354.1
  • GENBANK/VDB32352.1
  • GENBANK/VDB32351.1
  • GENBANK/VDB32353.1
  • GENBANK/QEH00205.1
  • GENBANK/YP_009272954.1
  • GENBANK/YP_007392342.1
  • GENBANK/NP_938237
  • GENBANK/YP_007392440.1
  • GENBANK/WP_016068584.1
  • GENBANK/YP_007392740.1
  • GENBANK/WP_043884810
  • GENBANK/ACD38920.1
  • GENBANK/AFC22483.1
  • GENBANK/WP_031500045.1
  • GENBANK/KEK29119
  • GENBANK/WP_038819808.1
  • GENBANK/ABR13388.1
  • GENBANK/EGE18854.1
  • GENBANK/AKI27193.1
  • GENBANK/YP_007392738.1
  • GENBANK/YP_007392439.1
  • GENBANK/YP_950454.1
  • GENBANK/NP_938238.1
  • GENBANK/WP_074973300.1
  • GENBANK/WP_087937214.1
  • GENBANK/WP_087937215.1
  • GENBANK/WP_064584002.1
  • GENBANK/AKG19229.1
  • GENBANK/NP_666582.1
  • GENBANK/WP_046701302.1
  • GENBANK/AKG19228.1
  • GENBANK/AKG19230.1
  • GENBANK/WP_046699156.1
  • GENBANK/WP_046699157.1