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dc.contributor.authorChatterjee, Pranam
dc.contributor.authorLee, Jooyoung
dc.contributor.authorNip, Lisa
dc.contributor.authorKoseki, Sabrina R. T.
dc.contributor.authorTysinger, Emma
dc.contributor.authorSontheimer, Erik J.
dc.contributor.authorJacobson, Joseph M.
dc.contributor.authorJakimo, Noah
dc.date2022-08-11T08:09:56.000
dc.date.accessioned2022-08-23T16:49:30Z
dc.date.available2022-08-23T16:49:30Z
dc.date.issued2020-05-18
dc.date.submitted2020-06-16
dc.identifier.citation<p>Chatterjee P, Lee J, Nip L, Koseki SRT, Tysinger E, Sontheimer EJ, Jacobson JM, Jakimo N. A Cas9 with PAM recognition for adenine dinucleotides. Nat Commun. 2020 May 18;11(1):2474. doi: 10.1038/s41467-020-16117-8. PMID: 32424114; PMCID: PMC7235249. <a href="https://doi.org/10.1038/s41467-020-16117-8">Link to article on publisher's site</a></p>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/s41467-020-16117-8
dc.identifier.pmid32424114
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41476
dc.description.abstractCRISPR-associated (Cas) DNA-endonucleases are remarkably effective tools for genome engineering, but have limited target ranges due to their protospacer adjacent motif (PAM) requirements. We demonstrate a critical expansion of the targetable sequence space for a type II-A CRISPR-associated enzyme through identification of the natural 5[Formula: see text]-NAAN-3[Formula: see text] PAM preference of Streptococcus macacae Cas9 (SmacCas9). To achieve efficient editing activity, we graft the PAM-interacting domain of SmacCas9 to its well-established ortholog from Streptococcus pyogenes (SpyCas9), and further engineer an increased efficiency variant (iSpyMac) for robust genome editing activity. We establish that our hybrids can target all adenine dinucleotide PAM sequences and possess robust and accurate editing capabilities in human cells.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32424114&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights© The Author(s) 2020. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCRISPR-Cas9 genome editing
dc.subjectComputational biology and bioinformatics
dc.subjectSynthetic biology
dc.subjectBioinformatics
dc.subjectComputational Biology
dc.subjectEnzymes and Coenzymes
dc.subjectGenetic Phenomena
dc.subjectGenetics and Genomics
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.titleA Cas9 with PAM recognition for adenine dinucleotides
dc.typeArticle
dc.source.journaltitleNature communications
dc.source.volume11
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5274&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4255
dc.identifier.contextkey18127122
refterms.dateFOA2022-08-23T16:49:30Z
html.description.abstract<p>CRISPR-associated (Cas) DNA-endonucleases are remarkably effective tools for genome engineering, but have limited target ranges due to their protospacer adjacent motif (PAM) requirements. We demonstrate a critical expansion of the targetable sequence space for a type II-A CRISPR-associated enzyme through identification of the natural 5[Formula: see text]-NAAN-3[Formula: see text] PAM preference of Streptococcus macacae Cas9 (SmacCas9). To achieve efficient editing activity, we graft the PAM-interacting domain of SmacCas9 to its well-established ortholog from Streptococcus pyogenes (SpyCas9), and further engineer an increased efficiency variant (iSpyMac) for robust genome editing activity. We establish that our hybrids can target all adenine dinucleotide PAM sequences and possess robust and accurate editing capabilities in human cells.</p>
dc.identifier.submissionpathoapubs/4255
dc.contributor.departmentRNA Therapeutics Institute
dc.source.pages2474


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© The Author(s) 2020. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © The Author(s) 2020. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.