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Enabling large-scale genome editing at repetitive elements by reducing DNA nicking

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dc.contributor.author Smith, Cory J.
dc.contributor.author Castanon, Oscar
dc.contributor.author Said, Khaled
dc.contributor.author Volf, Verena
dc.contributor.author Khoshakhlagh, Parastoo
dc.contributor.author Hornick, Amanda
dc.contributor.author Ferreira, Raphael
dc.contributor.author Wu, Chun-Ting
dc.contributor.author Güell Cargol, Marc, 1982-
dc.contributor.author Garg, Shilpa
dc.contributor.author Ng, Alex H. M.
dc.contributor.author Myllykallio, Hannu
dc.contributor.author Church, George M.
dc.date.accessioned 2020-06-04T06:23:29Z
dc.date.available 2020-06-04T06:23:29Z
dc.date.issued 2020
dc.identifier.citation Smith CJ, Castanon O, Said K, Volf V, Khoshakhlagh P, Hornick A, Ferreira R, Wu CT, Güell M, Garg S, Ng AHM, Myllykallio H, Church GM. Enabling large-scale genome editing at repetitive elements by reducing DNA nicking. Nucleic Acids Res. 2020; 48(9):5183-95. DOI: 10.1093/nar/gkaa239
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10230/44895
dc.description.abstract To extend the frontier of genome editing and enable editing of repetitive elements of mammalian genomes, we made use of a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks and single-strand breaks. We used a set of gRNAs targeting repetitive elements-ranging in target copy number from about 32 to 161 000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to ∼13 200 and ∼12 200 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof Nucleic Acids Res. 2020; 48(9):5183-95
dc.rights © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Enabling large-scale genome editing at repetitive elements by reducing DNA nicking
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/nar/gkaa239
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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