{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:09:38Z","timestamp":1787008178822,"version":"build-2736575974"},"reference-count":42,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The CRISPR Journal"],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:p>\n                    Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in either the\n                    <jats:italic toggle=\"yes\">TSC1<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">TSC2<\/jats:italic>\n                    genes. Though TSC causes the formation of nonmalignant tumors throughout multiple organs, the most frequent causes of mortality and morbidity are due to neurological complications. In two-thirds of cases, TSC occurs sporadically and\n                    <jats:italic toggle=\"yes\">TSC2<\/jats:italic>\n                    pathogenic variants are approximately three times more prevalent than\n                    <jats:italic toggle=\"yes\">TSC1<\/jats:italic>\n                    pathogenic variants. Here, we utilized CRISPR-Cas9-mediated homology directed repair in patient induced pluripotent stem cells (iPSCs) to correct two types of\n                    <jats:italic toggle=\"yes\">TSC2<\/jats:italic>\n                    pathogenic variants generating two isogenic lines. In one line, we corrected a splice acceptor variant (c.2743-1G&gt;A), which causes the skipping of coding exon 23 and subsequent frameshift and introduction of a stop codon in coding exon 25. In the second line, we corrected a missense variant in coding exon 40 within the GTPase-activating protein domain (c.5228G&gt;A, p.R1743Q). The generation of TSC2 patient iPSCs in parallel with their corresponding CRISPR-corrected isogenic lines will be an important tool for disease modeling applications and for developing therapeutics.\n                  <\/jats:p>","DOI":"10.1089\/crispr.2024.0079","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T04:10:47Z","timestamp":1733803847000},"page":"60-70","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["CRISPR-Cas9-Mediated Correction of\n                    <i>TSC2<\/i>\n                    Pathogenic Variants in iPSCs from Patients with Tuberous Sclerosis Complex Type 2"],"prefix":"10.1177","volume":"8","author":[{"given":"Gongbo","family":"Guo","sequence":"first","affiliation":[{"name":"The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Moser","sequence":"additional","affiliation":[{"name":"The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lincoln","family":"Chifamba","sequence":"additional","affiliation":[{"name":"The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Julian","sequence":"additional","affiliation":[{"name":"The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Teierle","sequence":"additional","affiliation":[{"name":"Division of Hematology, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prajwal","family":"Rajappa","sequence":"additional","affiliation":[{"name":"The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecelia","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-4128","authenticated-orcid":false,"given":"Mark E.","family":"Hester","sequence":"additional","affiliation":[{"name":"The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, Ohio, USA."},{"name":"Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA."},{"name":"Department of Neuroscience, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2021.07.011"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2020.00039"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15816"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.35"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20522-4"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra055323"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61279-9"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00069-1"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/17562864211031100"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/316951"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201402"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.27.16409"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.07.007"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22951"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00078"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.10.003"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a035659"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-020-0320-2"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12519-022-00576-8"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-019-0311-3"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.11.019"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0642-19.2019"},{"key":"e_1_3_6_25_2","article-title":"Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit","author":"Brown JA","year":"2023","unstructured":"Brown JA, , Faley SL, , Judge M, et al. Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit. bioRxiv, 2023; doi: 10.1101\/2023.12.15.571738","journal-title":"bioRxiv"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.054"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf5546"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgeed.2021.630600"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.042317"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01126-2"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4937689"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12836-9"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022434"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12030956"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0139-y"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.02.020"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.68"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0018-4"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12452"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01493.x"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22326"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-019-9289-6"},{"key":"e_1_3_6_43_2","article-title":"Single-stranded DNA with internal base modifications mediates highly efficient gene insertion in primary cells","author":"Kanke KL","year":"2024","unstructured":"Kanke KL, , Rayner RE, , Abel E, et al. Single-stranded DNA with internal base modifications mediates highly efficient gene insertion in primary cells. bioRxiv, 2024; doi: 10.1101\/2024.02.01.578476","journal-title":"bioRxiv"}],"container-title":["The CRISPR Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/crispr.2024.0079","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/crispr.2024.0079","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/crispr.2024.0079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:00:40Z","timestamp":1777644040000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/crispr.2024.0079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,1]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2,1]]}},"alternative-id":["10.1089\/crispr.2024.0079"],"URL":"https:\/\/doi.org\/10.1089\/crispr.2024.0079","relation":{},"ISSN":["2573-1599","2573-1602"],"issn-type":[{"value":"2573-1599","type":"print"},{"value":"2573-1602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,1]]}}}