{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:27Z","timestamp":1791928947416,"version":"4.3.4"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":62,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"UNC Royster Society of Fellows"},{"DOI":"10.13039\/100001951","name":"Angelman Syndrome Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001951","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["631904"],"award-info":[{"award-number":["631904"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R01NS109304"],"award-info":[{"award-number":["1R01NS109304"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-52498-4","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:44:59Z","timestamp":1778748299000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nickase NmCas9 unsilences paternal Ube3a in a mouse model of Angelman syndrome without causing AAV vector integration"],"prefix":"10.1038","volume":"16","author":[{"given":"Hannah O.","family":"Bazick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas M.","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Zylka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"52498_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/hum.2023.29263.bfs","volume":"35","author":"ACASGEVY Philippidis","year":"2024","unstructured":"Philippidis, A. C. A. S. G. E. V. Y. Makes History as FDA Approves First CRISPR\/Cas9 Genome Edited Therapy. Hum. Gene Ther. 35, 1\u20134. https:\/\/doi.org\/10.1089\/hum.2023.29263.bfs (2024).","journal-title":"Hum. Gene Ther."},{"key":"52498_CR2","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nbt.2507","volume":"31","author":"SW Cho","year":"2013","unstructured":"Cho, S. W., Kim, S., Kim, J. M. & Kim, J. S. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat. Biotechnol. 31, 230\u2013232. https:\/\/doi.org\/10.1038\/nbt.2507 (2013).","journal-title":"Nat. Biotechnol."},{"key":"52498_CR3","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"L Cong","year":"2013","unstructured":"Cong, L. et al. Multiplex genome engineering using CRISPR\/Cas systems. Science 339, 819\u2013823. https:\/\/doi.org\/10.1126\/science.1231143 (2013).","journal-title":"Science"},{"key":"52498_CR4","doi-asserted-by":"publisher","first-page":"1258096","DOI":"10.1126\/science.1258096","volume":"346","author":"JA Doudna","year":"2014","unstructured":"Doudna, J. A. & Charpentier, E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096. https:\/\/doi.org\/10.1126\/science.1258096 (2014).","journal-title":"Science"},{"key":"52498_CR5","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","volume":"157","author":"PD Hsu","year":"2014","unstructured":"Hsu, P. D., Lander, E. S. & Zhang, F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262\u20131278. https:\/\/doi.org\/10.1016\/j.cell.2014.05.010 (2014).","journal-title":"Cell"},{"key":"52498_CR6","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","volume":"337","author":"M Jinek","year":"2012","unstructured":"Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816\u2013821. https:\/\/doi.org\/10.1126\/science.1225829 (2012).","journal-title":"Science"},{"key":"52498_CR7","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1126\/science.1232033","volume":"339","author":"P Mali","year":"2013","unstructured":"Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339, 823\u2013826. https:\/\/doi.org\/10.1126\/science.1232033 (2013).","journal-title":"Science"},{"key":"52498_CR8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/nbt.2842","volume":"32","author":"JD Sander","year":"2014","unstructured":"Sander, J. D. & Joung, J. K. CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol. 32, 347\u2013355. https:\/\/doi.org\/10.1038\/nbt.2842 (2014).","journal-title":"Nat. Biotechnol."},{"key":"52498_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.09.032","author":"HO Bazick","year":"2024","unstructured":"Bazick, H. O., Mao, H., Niehaus, J. K., Wolter, J. M. & Zylka, M. J. AAV vector-derived elements integrate into Cas9-generated double strand breaks and disrupt gene transcription. Mol. Ther. https:\/\/doi.org\/10.1016\/j.ymthe.2024.09.032 (2024).","journal-title":"Mol. Ther."},{"key":"52498_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s42003-019-0300-2","volume":"2","author":"R Ono","year":"2019","unstructured":"Ono, R. et al. Exosome-mediated horizontal gene transfer occurs in double-strand break repair during genome editing. Commun. Biol. 2, 57. https:\/\/doi.org\/10.1038\/s42003-019-0300-2 (2019).","journal-title":"Commun. Biol."},{"key":"52498_CR11","doi-asserted-by":"publisher","first-page":"2898","DOI":"10.1016\/j.ymthe.2021.08.031","volume":"29","author":"DA Dalwadi","year":"2021","unstructured":"Dalwadi, D. A. et al. AAV integration in human hepatocytes. Mol. Ther. 29, 2898\u20132909. https:\/\/doi.org\/10.1016\/j.ymthe.2021.08.031 (2021).","journal-title":"Mol. Ther."},{"key":"52498_CR12","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.ymthe.2023.01.004","volume":"31","author":"BP Simpson","year":"2023","unstructured":"Simpson, B. P., Yrigollen, C. M., Izda, A. & Davidson, B. L. Targeted long-read sequencing captures CRISPR editing and AAV integration outcomes in brain. Mol. Ther. 31, 760\u2013773. https:\/\/doi.org\/10.1016\/j.ymthe.2023.01.004 (2023).","journal-title":"Mol. Ther."},{"key":"52498_CR13","doi-asserted-by":"publisher","first-page":"4002","DOI":"10.1038\/s41467-024-48111-9","volume":"15","author":"JC Park","year":"2024","unstructured":"Park, J. C. et al. Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways. Nat. Commun. 15, 4002. https:\/\/doi.org\/10.1038\/s41467-024-48111-9 (2024).","journal-title":"Nat. Commun."},{"key":"52498_CR14","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1038\/s41591-018-0049-z","volume":"24","author":"E Haapaniemi","year":"2018","unstructured":"Haapaniemi, E., Botla, S., Persson, J., Schmierer, B. & Taipale, J. CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response. Nat. Med. 24, 927\u2013930. https:\/\/doi.org\/10.1038\/s41591-018-0049-z (2018).","journal-title":"Nat. Med."},{"key":"52498_CR15","doi-asserted-by":"publisher","unstructured":"Provasek, V. E., Mitra, J., Malojirao, V. H. & Hegde, M. L. DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders. Int. J. Mol. Sci. 23 https:\/\/doi.org\/10.3390\/ijms23094653 (2022).","DOI":"10.3390\/ijms23094653"},{"key":"52498_CR16","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.dnarep.2008.03.007","volume":"7","author":"PO Frappart","year":"2008","unstructured":"Frappart, P. O. & McKinnon, P. J. Mouse models of DNA double-strand break repair and neurological disease. DNA Repair. (Amst). 7, 1051\u20131060. https:\/\/doi.org\/10.1016\/j.dnarep.2008.03.007 (2008).","journal-title":"DNA Repair. (Amst)"},{"key":"52498_CR17","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.4103\/1673-5374.215254","volume":"12","author":"D Stein","year":"2017","unstructured":"Stein, D. & Toiber, D. DNA damage and neurodegeneration: the unusual suspect. Neural Regen Res. 12, 1441\u20131442. https:\/\/doi.org\/10.4103\/1673-5374.215254 (2017).","journal-title":"Neural Regen Res."},{"key":"52498_CR18","doi-asserted-by":"publisher","unstructured":"Maynard, S. et al. DNA Repair, Aging, and Neurodegeneration. Cold Spring Harb Perspect. Med. 5 https:\/\/doi.org\/10.1101\/cshperspect.a025130 (2015).","DOI":"10.1101\/cshperspect.a025130"},{"key":"52498_CR19","doi-asserted-by":"publisher","first-page":"7726","DOI":"10.1038\/s41467-024-51906-5","volume":"15","author":"AA Polyzos","year":"2024","unstructured":"Polyzos, A. A. et al. Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain. Nat. Commun. 15, 7726. https:\/\/doi.org\/10.1038\/s41467-024-51906-5 (2024).","journal-title":"Nat. Commun."},{"key":"52498_CR20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/s41586-020-2835-2","volume":"587","author":"JM Wolter","year":"2020","unstructured":"Wolter, J. M. et al. Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA. Nature 587, 281\u2013284. https:\/\/doi.org\/10.1038\/s41586-020-2835-2 (2020).","journal-title":"Nature"},{"key":"52498_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.09.032","author":"HO Bazick","year":"2024","unstructured":"Bazick, H. O., Mao, H., Niehaus, J. K., Wolter, J. M. & Zylka, M. J. AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription. Mol. Ther. https:\/\/doi.org\/10.1016\/j.ymthe.2024.09.032 (2024).","journal-title":"Mol. Ther."},{"key":"52498_CR22","doi-asserted-by":"publisher","unstructured":"Schmid, R. S. et al. CRISPR\/Cas9 directed to the Ube3a antisense transcript improves Angelman syndrome phenotype in mice. J. Clin. Invest. 131 https:\/\/doi.org\/10.1172\/JCI142574 (2021).","DOI":"10.1172\/JCI142574"},{"key":"52498_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-025-00582-1","author":"HO Bazick","year":"2025","unstructured":"Bazick, H. O., James, L. M., Taylor-Blake, B., Wolter, J. M. & Zylka, M. J. Multi-targeting zinc finger nuclease vector unsilences paternal UBE3A in a mouse model of Angelman syndrome. Gene Ther. https:\/\/doi.org\/10.1038\/s41434-025-00582-1 (2025).","journal-title":"Gene Ther."},{"key":"52498_CR24","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1038\/s41467-023-37507-8","volume":"14","author":"J Lee","year":"2023","unstructured":"Lee, J. et al. Prime editing with genuine Cas9 nickases minimizes unwanted indels. Nat. Commun. 14, 1786. https:\/\/doi.org\/10.1038\/s41467-023-37507-8 (2023).","journal-title":"Nat. Commun."},{"key":"52498_CR25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s44321-023-00008-8","volume":"16","author":"L Torella","year":"2024","unstructured":"Torella, L. et al. Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1. EMBO Mol. Med. 16, 112\u2013131. https:\/\/doi.org\/10.1038\/s44321-023-00008-8 (2024).","journal-title":"EMBO Mol. Med."},{"key":"52498_CR26","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1093\/nar\/gks1333","volume":"41","author":"BP Belotserkovskii","year":"2013","unstructured":"Belotserkovskii, B. P. et al. Transcription blockage by homopurine DNA sequences: role of sequence composition and single-strand breaks. Nucleic Acids Res. 41, 1817\u20131828. https:\/\/doi.org\/10.1093\/nar\/gks1333 (2013).","journal-title":"Nucleic Acids Res."},{"key":"52498_CR27","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1128\/MCB.00897-09","volume":"30","author":"D Roy","year":"2010","unstructured":"Roy, D., Zhang, Z., Lu, Z., Hsieh, C. L. & Lieber, M. R. Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site. Mol. Cell. Biol. 30, 146\u2013159. https:\/\/doi.org\/10.1128\/MCB.00897-09 (2010).","journal-title":"Mol. Cell. Biol."},{"key":"52498_CR28","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1101\/gad.573310","volume":"24","author":"A El Hage","year":"2010","unstructured":"El Hage, A., French, S. L., Beyer, A. L. & Tollervey, D. Loss of Topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes Dev. 24, 1546\u20131558. https:\/\/doi.org\/10.1101\/gad.573310 (2010).","journal-title":"Genes Dev."},{"key":"52498_CR29","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/nrm.2017.43","volume":"18","author":"J Puc","year":"2017","unstructured":"Puc, J., Aggarwal, A. K. & Rosenfeld, M. G. Physiological functions of programmed DNA breaks in signal-induced transcription. Nat. Rev. Mol. Cell. Biol. 18, 471\u2013476. https:\/\/doi.org\/10.1038\/nrm.2017.43 (2017).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"52498_CR30","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1016\/j.ymthe.2024.03.006","volume":"32","author":"J Klermund","year":"2024","unstructured":"Klermund, J. et al. On- and off-target effects of paired CRISPR-Cas nickase in primary human cells. Mol. Ther. 32, 1298\u20131310. https:\/\/doi.org\/10.1016\/j.ymthe.2024.03.006 (2024).","journal-title":"Mol. Ther."},{"key":"52498_CR31","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nmeth.2857","volume":"11","author":"B Shen","year":"2014","unstructured":"Shen, B. et al. Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat. Methods. 11, 399\u2013402. https:\/\/doi.org\/10.1038\/nmeth.2857 (2014).","journal-title":"Nat. Methods"},{"key":"52498_CR32","doi-asserted-by":"publisher","unstructured":"Shadfar, S., Brocardo, M. & Atkin, J. D. The Complex Mechanisms by Which Neurons Die Following DNA Damage in Neurodegenerative Diseases. Int. J. Mol. Sci. 23 https:\/\/doi.org\/10.3390\/ijms23052484 (2022).","DOI":"10.3390\/ijms23052484"},{"key":"52498_CR33","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.cell.2014.02.001","volume":"156","author":"H Nishimasu","year":"2014","unstructured":"Nishimasu, H. et al. Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156, 935\u2013949. https:\/\/doi.org\/10.1016\/j.cell.2014.02.001 (2014).","journal-title":"Cell"},{"key":"52498_CR34","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1038\/s42003-025-08794-2","volume":"8","author":"JM Wolter","year":"2025","unstructured":"Wolter, J. M. et al. AAV-dCas9 vector unsilences paternal Ube3a in neurons by impeding Ube3a-ATS transcription. Commun. Biol. 8, 1332. https:\/\/doi.org\/10.1038\/s42003-025-08794-2 (2025).","journal-title":"Commun. Biol."},{"key":"52498_CR35","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1038\/s41594-023-01090-9","volume":"30","author":"I Zukher","year":"2023","unstructured":"Zukher, I., Dujardin, G., Sousa-Luis, R. & Proudfoot, N. J. Elongation roadblocks mediated by dCas9 across human genes modulate transcription and nascent RNA processing. Nat. Struct. Mol. Biol. 30, 1536\u20131548. https:\/\/doi.org\/10.1038\/s41594-023-01090-9 (2023).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"52498_CR36","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1038\/s41587-023-01974-7","volume":"42","author":"JA Greig","year":"2024","unstructured":"Greig, J. A. et al. Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration. Nat. Biotechnol. 42, 1232\u20131242. https:\/\/doi.org\/10.1038\/s41587-023-01974-7 (2024).","journal-title":"Nat. Biotechnol."},{"key":"52498_CR37","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1016\/j.ymthe.2022.06.004","volume":"30","author":"DE Sabatino","year":"2022","unstructured":"Sabatino, D. E. et al. Evaluating the state of the science for adeno-associated virus integration: An integrated perspective. Mol. Ther. 30, 2646\u20132663. https:\/\/doi.org\/10.1016\/j.ymthe.2022.06.004 (2022).","journal-title":"Mol. Ther."},{"key":"52498_CR38","doi-asserted-by":"publisher","first-page":"4439","DOI":"10.1038\/s41467-019-12449-2","volume":"10","author":"KS Hanlon","year":"2019","unstructured":"Hanlon, K. S. et al. High levels of AAV vector integration into CRISPR-induced DNA breaks. Nat. Commun. 10, 4439. https:\/\/doi.org\/10.1038\/s41467-019-12449-2 (2019).","journal-title":"Nat. Commun."},{"key":"52498_CR39","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.1182\/blood.2022017378","volume":"141","author":"A Calabria","year":"2023","unstructured":"Calabria, A. et al. Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci in mice. Blood 141, 2316\u20132329. https:\/\/doi.org\/10.1182\/blood.2022017378 (2023).","journal-title":"Blood"},{"key":"52498_CR40","doi-asserted-by":"publisher","unstructured":"Ferrari, S. et al. Choice of template delivery mitigates the genotoxic risk and adverse impact of editing in human hematopoietic stem cells. Cell Stem Cell 29, 1428\u20131444 e1429 (2022). https:\/\/doi.org\/10.1016\/j.stem.2022.09.001","DOI":"10.1016\/j.stem.2022.09.001"},{"key":"52498_CR41","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1186\/s12864-020-6655-4","volume":"21","author":"C Breton","year":"2020","unstructured":"Breton, C., Clark, P. M., Wang, L., Greig, J. A. & Wilson, J. M. ITR-Seq, a next-generation sequencing assay, identifies genome-wide DNA editing sites in vivo following adeno-associated viral vector-mediated genome editing. BMC Genom. 21, 239. https:\/\/doi.org\/10.1186\/s12864-020-6655-4 (2020).","journal-title":"BMC Genom."},{"key":"52498_CR42","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.tig.2021.02.008","volume":"37","author":"C Xue","year":"2021","unstructured":"Xue, C. & Greene, E. C. DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing. Trends Genet. 37, 639\u2013656. https:\/\/doi.org\/10.1016\/j.tig.2021.02.008 (2021).","journal-title":"Trends Genet."},{"key":"52498_CR43","doi-asserted-by":"publisher","first-page":"1410791","DOI":"10.3389\/fnana.2024.1410791","volume":"18","author":"C Gonzalez Ramirez","year":"2024","unstructured":"Gonzalez Ramirez, C. et al. Regional and cellular organization of the autism-associated protein UBE3A\/E6AP and its antisense transcript in the brain of the developing rhesus monkey. Front. Neuroanat. 18, 1410791. https:\/\/doi.org\/10.3389\/fnana.2024.1410791 (2024).","journal-title":"Front. Neuroanat."},{"key":"52498_CR44","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nmeth.3284","volume":"12","author":"D Kim","year":"2015","unstructured":"Kim, D. et al. Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat. Methods. 12, 237\u2013243. https:\/\/doi.org\/10.1038\/nmeth.3284 (2015). 231 p following 243.","journal-title":"Nat. Methods"},{"key":"52498_CR45","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1101\/gr.199588.115","volume":"26","author":"D Kim","year":"2016","unstructured":"Kim, D., Kim, S., Kim, S., Park, J. & Kim, J. S. Genome-wide target specificities of CRISPR-Cas9 nucleases revealed by multiplex Digenome-seq. Genome Res. 26, 406\u2013415. https:\/\/doi.org\/10.1101\/gr.199588.115 (2016).","journal-title":"Genome Res."},{"key":"52498_CR46","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/nmeth.4262","volume":"14","author":"J Park","year":"2017","unstructured":"Park, J. et al. Digenome-seq web tool for profiling CRISPR specificity. Nat. Methods. 14, 548\u2013549. https:\/\/doi.org\/10.1038\/nmeth.4262 (2017).","journal-title":"Nat. Methods"},{"key":"52498_CR47","doi-asserted-by":"publisher","first-page":"18511","DOI":"10.1074\/jbc.M313598200","volume":"279","author":"SD Kathe","year":"2004","unstructured":"Kathe, S. D., Shen, G. P. & Wallace, S. S. Single-stranded breaks in DNA but not oxidative DNA base damages block transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts. J. Biol. Chem. 279, 18511\u201318520. https:\/\/doi.org\/10.1074\/jbc.M313598200 (2004).","journal-title":"J. Biol. Chem."},{"key":"52498_CR48","doi-asserted-by":"publisher","first-page":"e0156439","DOI":"10.1371\/journal.pone.0156439","volume":"11","author":"AM Mabb","year":"2016","unstructured":"Mabb, A. M. et al. Topoisomerase 1 Regulates Gene Expression in Neurons through Cleavage Complex-Dependent and -Independent Mechanisms. PLoS One. 11, e0156439. https:\/\/doi.org\/10.1371\/journal.pone.0156439 (2016).","journal-title":"PLoS One"},{"key":"52498_CR49","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nature10726","volume":"481","author":"HS Huang","year":"2011","unstructured":"Huang, H. S. et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481, 185\u2013189. https:\/\/doi.org\/10.1038\/nature10726 (2011).","journal-title":"Nature"},{"key":"52498_CR50","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nature12504","volume":"501","author":"IF King","year":"2013","unstructured":"King, I. F. et al. Topoisomerases facilitate transcription of long genes linked to autism. Nature 501, 58\u201362. https:\/\/doi.org\/10.1038\/nature12504 (2013).","journal-title":"Nature"},{"key":"52498_CR51","doi-asserted-by":"publisher","first-page":"13938","DOI":"10.1073\/pnas.1305426110","volume":"110","author":"WT Powell","year":"2013","unstructured":"Powell, W. T. et al. R-loop formation at Snord116 mediates topotecan inhibition of Ube3a-antisense and allele-specific chromatin decondensation. Proc. Natl. Acad. Sci. U S A. 110, 13938\u201313943. https:\/\/doi.org\/10.1073\/pnas.1305426110 (2013).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"52498_CR52","doi-asserted-by":"publisher","first-page":"9883","DOI":"10.1038\/s41467-025-66058-3","volume":"16","author":"GN Ramadoss","year":"2025","unstructured":"Ramadoss, G. N. et al. Characterizing and controlling CRISPR repair outcomes in nondividing human cells. Nat. Commun. 16, 9883. https:\/\/doi.org\/10.1038\/s41467-025-66058-3 (2025).","journal-title":"Nat. Commun."},{"key":"52498_CR53","doi-asserted-by":"publisher","unstructured":"Rotaru, D. C., Wallaard, I., de Vries, M., van der Bie, J. & Elgersma, Y. UBE3A expression during early postnatal brain development is required for proper dorsomedial striatal maturation. JCI Insight. 8 https:\/\/doi.org\/10.1172\/jci.insight.166073 (2023).","DOI":"10.1172\/jci.insight.166073"},{"key":"52498_CR54","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1172\/JCI80554","volume":"125","author":"S Silva-Santos","year":"2015","unstructured":"Silva-Santos, S. et al. Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model. J. Clin. Invest. 125, 2069\u20132076. https:\/\/doi.org\/10.1172\/JCI80554 (2015).","journal-title":"J. Clin. Invest."},{"key":"52498_CR55","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13229-019-0277-1","volume":"10","author":"M Sonzogni","year":"2019","unstructured":"Sonzogni, M. et al. Delayed loss of UBE3A reduces the expression of Angelman syndrome-associated phenotypes. Mol. Autism. 10, 23. https:\/\/doi.org\/10.1186\/s13229-019-0277-1 (2019).","journal-title":"Mol. Autism"},{"key":"52498_CR56","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1093\/bioinformatics\/btu048","volume":"30","author":"S Bae","year":"2014","unstructured":"Bae, S., Park, J. & Kim, J. S. Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics 30, 1473\u20131475. https:\/\/doi.org\/10.1093\/bioinformatics\/btu048 (2014).","journal-title":"Bioinformatics"},{"key":"52498_CR57","doi-asserted-by":"publisher","unstructured":"Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience 10 https:\/\/doi.org\/10.1093\/gigascience\/giab008 (2021).","DOI":"10.1093\/gigascience\/giab008"},{"key":"52498_CR58","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae974","author":"G Perez","year":"2024","unstructured":"Perez, G. et al. The UCSC Genome Browser database: 2025 update. Nucleic Acids Res. https:\/\/doi.org\/10.1093\/nar\/gkae974 (2024).","journal-title":"Nucleic Acids Res."},{"key":"52498_CR59","doi-asserted-by":"publisher","first-page":"15644","DOI":"10.1073\/pnas.1313587110","volume":"110","author":"Z Hou","year":"2013","unstructured":"Hou, Z. et al. Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proc. Natl. Acad. Sci. U S A. 110, 15644\u201315649. https:\/\/doi.org\/10.1073\/pnas.1313587110 (2013).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"52498_CR60","doi-asserted-by":"publisher","first-page":"275","DOI":"10.18388\/abp.2012_2151","volume":"59","author":"A Carbone","year":"2012","unstructured":"Carbone, A., Fioretti, F. M., Fucci, L., Ausio, J. & Piscopo, M. High efficiency method to obtain supercoiled DNA with a commercial plasmid purification kit. Acta Biochim. Pol. 59, 275\u2013278 (2012).","journal-title":"Acta Biochim. Pol."},{"key":"52498_CR61","doi-asserted-by":"publisher","unstructured":"Gao, Y. et al. Plug-and-Play Protein Modification Using Homology-Independent Universal Genome Engineering. Neuron 103, 583\u2013597 e588 (2019). https:\/\/doi.org\/10.1016\/j.neuron.2019.05.047","DOI":"10.1016\/j.neuron.2019.05.047"},{"key":"52498_CR62","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1126\/science.aag0821","volume":"353","author":"A Uezu","year":"2016","unstructured":"Uezu, A. et al. Identification of an elaborate complex mediating postsynaptic inhibition. Science 353, 1123\u20131129. https:\/\/doi.org\/10.1126\/science.aag0821 (2016).","journal-title":"Science"},{"key":"52498_CR63","doi-asserted-by":"publisher","unstructured":"Kim, H. et al. Rescue of behavioral and electrophysiological phenotypes in a Pitt-Hopkins syndrome mouse model by genetic restoration of Tcf4 expression. Elife 11 https:\/\/doi.org\/10.7554\/eLife.72290 (2022).","DOI":"10.7554\/eLife.72290"},{"key":"52498_CR64","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/hmg\/ddm288","volume":"17","author":"SV Dindot","year":"2008","unstructured":"Dindot, S. V., Antalffy, B. A., Bhattacharjee, M. B. & Beaudet, A. L. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum. Mol. Genet. 17, 111\u2013118. https:\/\/doi.org\/10.1093\/hmg\/ddm288 (2008).","journal-title":"Hum. Mol. Genet."},{"key":"52498_CR65","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s10661-016-5405-1","volume":"188","author":"AS Dickerson","year":"2016","unstructured":"Dickerson, A. S. et al. Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic. Environ. Monit. Assess. 188, 407. https:\/\/doi.org\/10.1007\/s10661-016-5405-1 (2016).","journal-title":"Environ. Monit. Assess."},{"key":"52498_CR66","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0166-0934(95)00035-s","volume":"54","author":"AB Bahnson","year":"1995","unstructured":"Bahnson, A. B. et al. Centrifugal enhancement of retroviral mediated gene transfer. J. Virol. Methods. 54, 131\u2013143. https:\/\/doi.org\/10.1016\/0166-0934(95)00035-s (1995).","journal-title":"J. Virol. Methods"},{"key":"52498_CR67","doi-asserted-by":"publisher","unstructured":"Kim, J. Y., Grunke, S. D., Levites, Y., Golde, T. E. & Jankowsky, J. L. Intracerebroventricular viral injection of the neonatal mouse brain for persistent and widespread neuronal transduction. J. Vis. Exp. 51863 https:\/\/doi.org\/10.3791\/51863 (2014).","DOI":"10.3791\/51863"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-52498-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-52498-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-52498-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:28:09Z","timestamp":1784068089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-52498-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["52498"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-52498-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"18 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"22090"}}