Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells

We describe a strategy to boost the efficiency of gene editing via homology-directed repair (HDR) by covalently modifying the template DNA with interstrand crosslinks. Crosslinked templates (xHDRTs) increase Cas9-mediated editing efficiencies by up to fivefold in K562, HEK293T, U2OS, iPS and primary...

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Autores principales: Ghasemi, Hannah I., Bacal, Julien, Yoon, Amanda C., Tavasoli, Katherine U., Cruz, Carmen, Vu, Jonathan T., Gardner, Brooke M., Richardson, Chris D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460463/
https://www.ncbi.nlm.nih.gov/pubmed/36849829
http://dx.doi.org/10.1038/s41587-022-01654-y
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author Ghasemi, Hannah I.
Bacal, Julien
Yoon, Amanda C.
Tavasoli, Katherine U.
Cruz, Carmen
Vu, Jonathan T.
Gardner, Brooke M.
Richardson, Chris D.
author_facet Ghasemi, Hannah I.
Bacal, Julien
Yoon, Amanda C.
Tavasoli, Katherine U.
Cruz, Carmen
Vu, Jonathan T.
Gardner, Brooke M.
Richardson, Chris D.
author_sort Ghasemi, Hannah I.
collection PubMed
description We describe a strategy to boost the efficiency of gene editing via homology-directed repair (HDR) by covalently modifying the template DNA with interstrand crosslinks. Crosslinked templates (xHDRTs) increase Cas9-mediated editing efficiencies by up to fivefold in K562, HEK293T, U2OS, iPS and primary T cells. Increased editing from xHDRTs is driven by events on the template molecule and requires ataxia telangiectasia and Rad3-related (ATR) kinase and components of the Fanconi anemia pathway.
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spelling pubmed-104604632023-10-13 Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells Ghasemi, Hannah I. Bacal, Julien Yoon, Amanda C. Tavasoli, Katherine U. Cruz, Carmen Vu, Jonathan T. Gardner, Brooke M. Richardson, Chris D. Nat Biotechnol Brief Communication We describe a strategy to boost the efficiency of gene editing via homology-directed repair (HDR) by covalently modifying the template DNA with interstrand crosslinks. Crosslinked templates (xHDRTs) increase Cas9-mediated editing efficiencies by up to fivefold in K562, HEK293T, U2OS, iPS and primary T cells. Increased editing from xHDRTs is driven by events on the template molecule and requires ataxia telangiectasia and Rad3-related (ATR) kinase and components of the Fanconi anemia pathway. Nature Publishing Group US 2023-02-27 2023 /pmc/articles/PMC10460463/ /pubmed/36849829 http://dx.doi.org/10.1038/s41587-022-01654-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Ghasemi, Hannah I.
Bacal, Julien
Yoon, Amanda C.
Tavasoli, Katherine U.
Cruz, Carmen
Vu, Jonathan T.
Gardner, Brooke M.
Richardson, Chris D.
Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells
title Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells
title_full Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells
title_fullStr Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells
title_full_unstemmed Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells
title_short Interstrand crosslinking of homologous repair template DNA enhances gene editing in human cells
title_sort interstrand crosslinking of homologous repair template dna enhances gene editing in human cells
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460463/
https://www.ncbi.nlm.nih.gov/pubmed/36849829
http://dx.doi.org/10.1038/s41587-022-01654-y
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