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ファイル | 記述 | サイズ | フォーマット | |
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j.stemcr.2023.07.007.pdf | 4.05 MB | Adobe PDF | 見る/開く |
タイトル: | Dual CRISPR-Cas3 system for inducing multi-exon skipping in DMD patient-derived iPSCs |
著者: | Kita, Yuto Okuzaki, Yuya Naoe, Youichi Lee, Joseph Bang, Uikyu Okawa, Natsumi Ichiki, Akane Jonouchi, Tatsuya Sakurai, Hidetoshi https://orcid.org/0000-0002-5383-9366 (unconfirmed) Kojima, Yusuke https://orcid.org/0000-0001-7837-6102 (unconfirmed) Hotta, Akitsu https://orcid.org/0000-0002-2619-7441 (unconfirmed) |
著者名の別形: | 北, 悠人 奥嵜, 雄也 直江, 洋一 リー, ジョセフ パン, イギュ 大川, 夏実 市来, 明音 城之内, 達也 櫻井, 英俊 小島, 佑介 堀田, 秋津 |
キーワード: | DMD CRISPR-Cas3 genome editing gene therapy exon skipping |
発行日: | 12-Sep-2023 |
出版者: | Elsevier BV |
誌名: | Stem Cell Reports |
巻: | 18 |
号: | 9 |
開始ページ: | 1753 |
終了ページ: | 1765 |
抄録: | To restore dystrophin protein in various mutation patterns of Duchenne muscular dystrophy (DMD), the multi-exon skipping (MES) approach has been investigated. However, only limited techniques are available to induce a large deletion to cover the target exons spread over several hundred kilobases. Here, we utilized the CRISPR-Cas3 system for MES induction and showed that dual crRNAs could induce a large deletion at the dystrophin exon 45–55 region (∼340 kb), which can be applied to various types of DMD patients. We developed a two-color SSA-based reporter system for Cas3 to enrich the genome-edited cell population and demonstrated that MES induction restored dystrophin protein in DMD-iPSCs with three distinct mutations. Whole-genome sequencing and distance analysis detected no significant off-target deletion near the putative crRNA binding sites. Altogether, dual CRISPR-Cas3 is a promising tool to induce a gigantic genomic deletion and restore dystrophin protein via MES induction. |
記述: | DMD患者さん由来iPS細胞で複数のエクソンスキッピングを誘導するデュアルCRISPR-Cas3システムの開発. 京都大学プレスリリース. 2023-08-25. Exploring New Avenues in DMD Treatment: CRISPR-Cas3's Multi-Exon Skipping Approach. 京都大学プレスリリース. 2023-08-28. |
著作権等: | © 2023 The Authors. This is an open access article under the CC BY license. |
URI: | http://hdl.handle.net/2433/285066 |
DOI(出版社版): | 10.1016/j.stemcr.2023.07.007 |
PubMed ID: | 37625413 |
関連リンク: | https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/230825-000000.html https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/230828-100000.html |
出現コレクション: | 学術雑誌掲載論文等 |
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