Abstract
Clustered regularly interspaced short palindromic repeats (CRISPR) together with their accompanying cas (CRISPR-associated) genes are found frequently in bacteria and archaea, serving to defend against invading foreign DNA, such as viral genomes. CRISPR-Cas systems provide a uniquely powerful defense because they can adapt to newly encountered genomes. The adaptive ability of these systems has been exploited, leading to their development as highly effective tools for genome editing. The widespread use of CRISPR-Cas systems has driven a need for methods to control their activity. This review focuses on anti-CRISPRs (Acrs), proteins produced by viruses and other mobile genetic elements that can potently inhibit CRISPR-Cas systems. Discovered in 2013, there are now 54 distinct families of these proteins described, and the functional mechanisms of more than a dozen have been characterized in molecular detail. The investigation of Acrs is leading to a variety of practical applications and is providing exciting new insight into the biology of CRISPR-Cas systems.
Keywords:
Acr; CRISPR-Cas; anti-CRISPR; bacteriophage; genome editing; mobile genetic element.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Archaea / genetics
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Archaea / immunology
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Archaea / virology
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Bacteria / genetics
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Bacteria / immunology
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Bacteria / virology
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Biological Coevolution
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CRISPR-Associated Proteins / antagonists & inhibitors
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CRISPR-Associated Proteins / genetics
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CRISPR-Associated Proteins / metabolism
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CRISPR-Cas Systems / drug effects*
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DNA / antagonists & inhibitors
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DNA / chemistry
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DNA / genetics
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DNA / metabolism
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DNA Cleavage / drug effects
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Endodeoxyribonucleases / antagonists & inhibitors
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Endodeoxyribonucleases / genetics
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Endodeoxyribonucleases / metabolism
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Gene Editing / methods*
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Humans
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Models, Molecular
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Multigene Family
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Protein Binding
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Protein Multimerization / drug effects
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RNA, Guide, CRISPR-Cas Systems / genetics
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RNA, Guide, CRISPR-Cas Systems / metabolism
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / metabolism
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Small Molecule Libraries / pharmacology*
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Viral Proteins / chemistry
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Viral Proteins / genetics*
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Viral Proteins / metabolism
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Viral Proteins / pharmacology
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Viruses / genetics*
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Viruses / metabolism
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Viruses / pathogenicity
Substances
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Bacterial Proteins
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CRISPR-Associated Proteins
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RNA, Guide, CRISPR-Cas Systems
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Small Molecule Libraries
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Viral Proteins
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DNA
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Cas12a protein
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Endodeoxyribonucleases