RNA Therapeutics Institute; Program in Molecular Medicine; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Bioinformatics | Computational Biology | Enzymes and Coenzymes | Genomics | Nucleic Acids, Nucleotides, and Nucleosides
CRISPR-Cas9 systems provide powerful tools for genome editing. However, optimal employment of this technology will require control of Cas9 activity so that the timing, tissue specificity, and accuracy of editing may be precisely modulated. Anti-CRISPR proteins, which are small, naturally occurring inhibitors of CRISPR-Cas systems, are well suited for this purpose. A number of anti-CRISPR proteins have been shown to potently inhibit subgroups of CRISPR-Cas9 systems, but their maximal inhibitory activity is generally restricted to specific Cas9 homologs. Since Cas9 homologs vary in important properties, differing Cas9s may be optimal for particular genome-editing applications. To facilitate the practical exploitation of multiple Cas9 homologs, here we identify one anti-CRISPR, called AcrIIA5, that potently inhibits nine diverse type II-A and type II-C Cas9 homologs, including those currently used for genome editing. We show that the activity of AcrIIA5 results in partial in vivo cleavage of a single-guide RNA (sgRNA), suggesting that its mechanism involves RNA interaction.
Cas9, anti-CRISPR, bacteriophage, genome editing
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Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Cell Rep. 2019 Nov 12;29(7):1739-1746.e5. doi: 10.1016/j.celrep.2019.10.017. Link to article on publisher's site
Garcia B, Lee J, Edraki A, Hidalgo-Reyes Y, Erwood S, Mir A, Trost CN, Seroussi U, Stanley SY, Cohn RD, Claycomb JM, Sontheimer EJ, Maxwell KL, Davidson AR. (2019). Anti-CRISPR AcrIIA5 Potently Inhibits All Cas9 Homologs Used for Genome Editing. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.celrep.2019.10.017. Retrieved from https://escholarship.umassmed.edu/oapubs/4052
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
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