{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:21:17Z","timestamp":1791084077949,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020M3A9I4036072"],"award-info":[{"award-number":["2020M3A9I4036072"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A6A1A06046728"],"award-info":[{"award-number":["2020R1A6A1A06046728"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A2C3012908"],"award-info":[{"award-number":["2021R1A2C3012908"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021M3A9H3015389"],"award-info":[{"award-number":["2021M3A9H3015389"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prime editing is a versatile and precise genome editing technique that can directly copy desired genetic modifications into target DNA sites without the need for donor DNA. This technique holds great promise for the analysis of gene function, disease modeling, and the correction of pathogenic mutations in clinically relevant cells such as human pluripotent stem cells (hPSCs). Here, we comprehensively tested prime editing in hPSCs by generating a doxycycline-inducible prime editing platform. Prime editing successfully induced all types of nucleotide substitutions and small insertions and deletions, similar to observations in other human cell types. Moreover, we compared prime editing and base editing for correcting a disease-related mutation in induced pluripotent stem cells derived form a patient with \u03b1 1-antitrypsin (A1AT) deficiency. Finally, whole-genome sequencing showed that, unlike the cytidine deaminase domain of cytosine base editors, the reverse transcriptase domain of a prime editor does not lead to guide RNA-independent off-target mutations in the genome. Our results demonstrate that prime editing in hPSCs has great potential for complementing previously developed CRISPR genome editing tools.<\/jats:p>","DOI":"10.1093\/nar\/gkab1295","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T15:16:15Z","timestamp":1640099775000},"page":"1187-1197","source":"Crossref","is-referenced-by-count":82,"title":["Comprehensive analysis of prime editing outcomes in human embryonic stem cells"],"prefix":"10.1093","volume":"50","author":[{"given":"Omer","family":"Habib","sequence":"first","affiliation":[{"name":"Department of Chemistry and Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul 08826, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gizem","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul 08826, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gue-Ho","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul 08826, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3615-8566","authenticated-orcid":false,"given":"Sangsu","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul 08826, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,8]]},"reference":[{"key":"2022012517513962100_B1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-genet-112414-054926","article-title":"From genomics to gene therapy: induced pluripotent stem cells meet genome editing","volume":"49","author":"Hotta","year":"2015","journal-title":"Annu. Rev. Genet."},{"key":"2022012517513962100_B2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.stem.2016.04.013","article-title":"Induced pluripotent stem cells meet genome editing","volume":"18","author":"Hockemeyer","year":"2016","journal-title":"Cell Stem Cell"},{"key":"2022012517513962100_B3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cell.2016.10.044","article-title":"CRISPR-based technologies for the manipulation of eukaryotic genomes","volume":"168","author":"Komor","year":"2017","journal-title":"Cell"},{"key":"2022012517513962100_B4","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.cell.2018.09.010","article-title":"Stem cells, genome editing, and the path to translational medicine","volume":"175","author":"Soldner","year":"2018","journal-title":"Cell"},{"key":"2022012517513962100_B5","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"2022012517513962100_B6","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nbt.2507","article-title":"Targeted genome engineering in human cells with the cas9 RNA-guided endonuclease","volume":"31","author":"Cho","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2022012517513962100_B7","doi-asserted-by":"crossref","first-page":"e00471","DOI":"10.7554\/eLife.00471","article-title":"RNA-programmed genome editing in human cells","volume":"2","author":"Jinek","year":"2013","journal-title":"Elife"},{"key":"2022012517513962100_B8","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1232033","article-title":"RNA-guided human genome engineering via Cas9","volume":"339","author":"Mali","year":"2013","journal-title":"Science"},{"key":"2022012517513962100_B9","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/nbt.4192","article-title":"Repair of double-strand breaks induced by CRISPR\u2013Cas9 leads to large deletions and complex rearrangements","volume":"36","author":"Kosicki","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"2022012517513962100_B10","doi-asserted-by":"crossref","first-page":"8732","DOI":"10.1093\/nar\/gkab686","article-title":"Global detection of DNA repair outcomes induced by CRISPR\u2013Cas9","volume":"49","author":"Liu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2022012517513962100_B11","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s41591-018-0050-6","article-title":"p53 inhibits CRISPR\u2013Cas9 engineering in human pluripotent stem cells","volume":"24","author":"Ihry","year":"2018","journal-title":"Nat. Med."},{"key":"2022012517513962100_B12","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/s41591-018-0049-z","article-title":"CRISPR\u2013Cas9 genome editing induces a p53-mediated DNA damage response","volume":"24","author":"Haapaniemi","year":"2018","journal-title":"Nat. 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Biotechnol."},{"key":"2022012517513962100_B34","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.molp.2020.03.012","article-title":"Versatile nucleotides substitution in plant using an improved prime editing system","volume":"13","author":"Xu","year":"2020","journal-title":"Mol Plant"},{"key":"2022012517513962100_B35","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1111\/pbi.13395","article-title":"Precision genome engineering in rice using prime editing system","volume":"18","author":"Hua","year":"2020","journal-title":"Plant Biotechnol. J."},{"key":"2022012517513962100_B36","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/s41587-021-00868-w","article-title":"High-efficiency prime editing with optimized, paired pegRNAs in plants","volume":"39","author":"Lin","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"2022012517513962100_B37","doi-asserted-by":"crossref","first-page":"e202000940","DOI":"10.26508\/lsa.202000940","article-title":"Evaluating CRISPR-based prime editing for cancer modeling and CFTR repair in intestinal organoids","volume":"4","author":"Geurts","year":"2021","journal-title":"Life Sci. Alliance."},{"key":"2022012517513962100_B38","doi-asserted-by":"crossref","first-page":"e2021996118","DOI":"10.1073\/pnas.2021996118","article-title":"Precise genome engineering in Drosophila using prime editing","volume":"118","author":"Bosch","year":"2021","journal-title":"Proc. Natl. Acad. Sci. 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Eng."},{"key":"2022012517513962100_B42","doi-asserted-by":"crossref","first-page":"10576","DOI":"10.1093\/nar\/gkaa764","article-title":"Unbiased investigation of specificities of prime editing systems in human cells","volume":"48","author":"Kim","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022012517513962100_B43","article-title":"Dual-AAV delivering split prime editor system for in vivo genome editing","author":"Zhi","year":"2021","journal-title":"Mol. 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