Anti-CRISPR AcrIIA5 Potently Inhibits All Cas9 Homologs Used for Genome Editing
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Authors
Garcia, BiancaLee, Jooyoung
Edraki, Alireza
Hidalgo-Reyes, Yurima
Erwood, Steven
Mir, Aamir
Trost, Chantel N.
Seroussi, Uri
Stanley, Sabrina Y.
Cohn, Ronald D.
Claycomb, Julie M.
Sontheimer, Erik J.
Maxwell, Karen L.
Davidson, Alan R.
UMass Chan Affiliations
Graduate School of Biomedical SciencesProgram in Molecular Medicine
RNA Therapeutics Institute
Document Type
Journal ArticlePublication Date
2019-11-12Keywords
Cas9anti-CRISPR
bacteriophage
genome editing
Amino Acids, Peptides, and Proteins
Bioinformatics
Computational Biology
Enzymes and Coenzymes
Genomics
Nucleic Acids, Nucleotides, and Nucleosides
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Show full item recordAbstract
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.Source
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
DOI
10.1016/j.celrep.2019.10.017Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41266PubMed ID
31722192Related Resources
Rights
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/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2019.10.017
Scopus Count
Except where otherwise noted, this item's license is described as 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/).