5′-Modifications improve potency and efficacy of DNA donors for precision genome editing
Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as a therapeutic approach to correct mutations that cause disease. In its most precise form, genome editing can use cellular homology-directed repair (HDR) pathways to insert information from an ex...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:a4d2a8d974e94e189ee441394236bb612021-11-04T12:10:38Z5′-Modifications improve potency and efficacy of DNA donors for precision genome editing10.7554/eLife.722162050-084Xe72216https://doaj.org/article/a4d2a8d974e94e189ee441394236bb612021-10-01T00:00:00Zhttps://elifesciences.org/articles/72216https://doaj.org/toc/2050-084XNuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as a therapeutic approach to correct mutations that cause disease. In its most precise form, genome editing can use cellular homology-directed repair (HDR) pathways to insert information from an exogenously supplied DNA-repair template (donor) directly into a targeted genomic location. Unfortunately, particularly for long insertions, toxicity and delivery considerations associated with repair template DNA can limit HDR efficacy. Here, we explore chemical modifications to both double-stranded and single-stranded DNA-repair templates. We describe 5′-terminal modifications, including in its simplest form the incorporation of triethylene glycol (TEG) moieties, that consistently increase the frequency of precision editing in the germlines of three animal models (Caenorhabditis elegans, zebrafish, mice) and in cultured human cells.Krishna S GhantaZexiang ChenAamir MirGregoriy A DokshinPranathi M KrishnamurthyYeonsoo YoonJudith GallantPing XuXiao-Ou ZhangAhmet Rasit OzturkMasahiro ShinFeston IdriziPengpeng LiuHassan GneidAlireza EdrakiNathan D LawsonJaime A Rivera-PérezErik J SontheimerJonathan K WattsCraig C MelloeLife Sciences Publications LtdarticleCRISPRHDRmodified donorschemical modificationsgenome editingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
| institution |
DOAJ |
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DOAJ |
| language |
EN |
| topic |
CRISPR HDR modified donors chemical modifications genome editing Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
CRISPR HDR modified donors chemical modifications genome editing Medicine R Science Q Biology (General) QH301-705.5 Krishna S Ghanta Zexiang Chen Aamir Mir Gregoriy A Dokshin Pranathi M Krishnamurthy Yeonsoo Yoon Judith Gallant Ping Xu Xiao-Ou Zhang Ahmet Rasit Ozturk Masahiro Shin Feston Idrizi Pengpeng Liu Hassan Gneid Alireza Edraki Nathan D Lawson Jaime A Rivera-Pérez Erik J Sontheimer Jonathan K Watts Craig C Mello 5′-Modifications improve potency and efficacy of DNA donors for precision genome editing |
| description |
Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as a therapeutic approach to correct mutations that cause disease. In its most precise form, genome editing can use cellular homology-directed repair (HDR) pathways to insert information from an exogenously supplied DNA-repair template (donor) directly into a targeted genomic location. Unfortunately, particularly for long insertions, toxicity and delivery considerations associated with repair template DNA can limit HDR efficacy. Here, we explore chemical modifications to both double-stranded and single-stranded DNA-repair templates. We describe 5′-terminal modifications, including in its simplest form the incorporation of triethylene glycol (TEG) moieties, that consistently increase the frequency of precision editing in the germlines of three animal models (Caenorhabditis elegans, zebrafish, mice) and in cultured human cells. |
| format |
article |
| author |
Krishna S Ghanta Zexiang Chen Aamir Mir Gregoriy A Dokshin Pranathi M Krishnamurthy Yeonsoo Yoon Judith Gallant Ping Xu Xiao-Ou Zhang Ahmet Rasit Ozturk Masahiro Shin Feston Idrizi Pengpeng Liu Hassan Gneid Alireza Edraki Nathan D Lawson Jaime A Rivera-Pérez Erik J Sontheimer Jonathan K Watts Craig C Mello |
| author_facet |
Krishna S Ghanta Zexiang Chen Aamir Mir Gregoriy A Dokshin Pranathi M Krishnamurthy Yeonsoo Yoon Judith Gallant Ping Xu Xiao-Ou Zhang Ahmet Rasit Ozturk Masahiro Shin Feston Idrizi Pengpeng Liu Hassan Gneid Alireza Edraki Nathan D Lawson Jaime A Rivera-Pérez Erik J Sontheimer Jonathan K Watts Craig C Mello |
| author_sort |
Krishna S Ghanta |
| title |
5′-Modifications improve potency and efficacy of DNA donors for precision genome editing |
| title_short |
5′-Modifications improve potency and efficacy of DNA donors for precision genome editing |
| title_full |
5′-Modifications improve potency and efficacy of DNA donors for precision genome editing |
| title_fullStr |
5′-Modifications improve potency and efficacy of DNA donors for precision genome editing |
| title_full_unstemmed |
5′-Modifications improve potency and efficacy of DNA donors for precision genome editing |
| title_sort |
5′-modifications improve potency and efficacy of dna donors for precision genome editing |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/a4d2a8d974e94e189ee441394236bb61 |
| work_keys_str_mv |
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