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Genome-wide target specificity of CRISPR RNA-guided adenine base editors
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Daesik | - |
dc.contributor.author | Kim, Da-eun | - |
dc.contributor.author | Lee, Gyeorae | - |
dc.contributor.author | Cho, Sung-Ik | - |
dc.contributor.author | Kim, Jin-Soo | - |
dc.date.accessioned | 2020-04-27T13:02:33Z | - |
dc.date.available | 2020-04-27T13:02:33Z | - |
dc.date.created | 2020-04-08 | - |
dc.date.created | 2020-04-08 | - |
dc.date.issued | 2019-04 | - |
dc.identifier.citation | Nature Biotechnology, Vol.37 No.4, pp.430-435 | - |
dc.identifier.issn | 1087-0156 | - |
dc.identifier.other | 95257 | - |
dc.identifier.uri | https://hdl.handle.net/10371/165712 | - |
dc.description.abstract | Adenine base editors(1) enable efficient targeted adenine-to-guanine single nucleotide conversions to induce or correct point mutations in human cells, animals, and plants(1-4). Here we present a modified version of Digenome-seq, an in vitro method for identifying CRISPR (clustered regularly interspaced short palindromic repeats)-induced double-strand breaks using whole-genome sequencings(5-8), to assess genomewide target specificity of adenine base editors. To produce double-strand breaks at sites containing inosines, the products of adenine deamination, we treat human genomic DNA with an adenine base editor 7.10 protein-guide RNA complex and either endonuclease V or a combination of human alkyladenine DNA glycosylase and endonuclease VIII in vitro. Digenome-seq detects adenine base editor off-target sites with a substitution frequency of 0.1% or more. We show that adenine base editor 7.10, the cytosine base editor BE3, and unmodified CRISPR-associated protein 9 (Cas9) often recognize different off-target sites, highlighting the need for independent assessments of their genome-wide specificities(6). Using targeted sequencing, we also show that use of preassembled adenine base editor ribonucleoproteins, modified guide RNAs5,8-11, and Sniper/Cas9 (ref.(12)) reduces adenine base editor off-target activity in human cells. | - |
dc.language | 영어 | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Genome-wide target specificity of CRISPR RNA-guided adenine base editors | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 김진수 | - |
dc.identifier.doi | 10.1038/s41587-019-0050-1 | - |
dc.citation.journaltitle | Nature Biotechnology | - |
dc.identifier.wosid | 000463006000024 | - |
dc.identifier.scopusid | 2-s2.0-85062468203 | - |
dc.citation.endpage | 435 | - |
dc.citation.number | 4 | - |
dc.citation.startpage | 430 | - |
dc.citation.volume | 37 | - |
dc.identifier.sci | 000463006000024 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Kim, Jin-Soo | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ENDONUCLEASES | - |
dc.subject.keywordPlus | DNA | - |
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