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유전체교정연구단
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Genome-wide target specificities of CRISPR RNA-guided programmable deaminases

DC Field Value Language
dc.contributor.authorDaesik Kim-
dc.contributor.authorKayeong Lim-
dc.contributor.authorSang-Tae Kim-
dc.contributor.authorSun-heui Yoon-
dc.contributor.authorKyoungmi Kim-
dc.contributor.authorSeuk-Min Ryu-
dc.contributor.authorJin-Soo Kim-
dc.date.available2017-09-05T05:12:29Z-
dc.date.created2017-06-19-
dc.date.issued2017-05-
dc.identifier.issn1087-0156-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/3703-
dc.description.abstractCas9-linked deaminases, also called base editors, enable targeted mutation of single nucleotides in eukaryotic genomes. However, their off-target activity is largely unknown. Here we modify digested-genome sequencing (Digenome-seq) to assess the specificity of a programmable deaminase composed of a Cas9 nickase (nCas9) and the deaminase APOBEC1 in the human genome. Genomic DNA is treated with the base editor and a mixture of DNA-modifying enzymes in vitro to produce DNA double-strand breaks (DSBs) at uracil-containing sites. Off-target sites are then computationally identified from whole genome sequencing data. Testing seven different single guide RNAs (sgRNAs), we find that the rAPOBEC1-nCas9 base editor is highly specific, inducing cytosine-to-uracil conversions at only 18 ± 9 sites in the human genome for each sgRNA. Digenome-seq is sensitive enough to capture off-target sites with a substitution frequency of 0.1%. Notably, off-target sites of the base editors are often different from those of Cas9 alone, calling for independent assessment of their genome-wide specificities. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.-
dc.language영어-
dc.publisherNATURE PUBLISHING GROUP-
dc.titleGenome-wide target specificities of CRISPR RNA-guided programmable deaminases-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000400809800022-
dc.identifier.scopusid2-s2.0-85018935232-
dc.identifier.rimsid59668ko
dc.date.tcdate2018-10-01-
dc.contributor.affiliatedAuthorKayeong Lim-
dc.contributor.affiliatedAuthorSang-Tae Kim-
dc.contributor.affiliatedAuthorKyoungmi Kim-
dc.contributor.affiliatedAuthorSeuk-Min Ryu-
dc.contributor.affiliatedAuthorJin-Soo Kim-
dc.identifier.doi10.1038/nbt.3852-
dc.identifier.bibliographicCitationNATURE BIOTECHNOLOGY, v.35, no.5, pp.475 - 480-
dc.relation.isPartOfNATURE BIOTECHNOLOGY-
dc.citation.titleNATURE BIOTECHNOLOGY-
dc.citation.volume35-
dc.citation.number5-
dc.citation.startPage475-
dc.citation.endPage480-
dc.date.scptcdate2018-10-01-
dc.description.wostc29-
dc.description.scptc31-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.description.journalClass1-
dc.description.journalClass1-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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