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j.stemcr.2014.10.013.pdf | 2.45 MB | Adobe PDF | 見る/開く |
タイトル: | Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9 |
著者: | Li, Hongmei Lisa Fujimoto, Naoko Sasakawa, Noriko Shirai, Saya Ohkame, Tokiko Sakuma, Tetsushi https://orcid.org/0000-0003-0396-1563 (unconfirmed) Tanaka, Michihiro Amano, Naoki Watanabe, Akira https://orcid.org/0000-0002-4381-4229 (unconfirmed) Sakurai, Hidetoshi https://orcid.org/0000-0002-5383-9366 (unconfirmed) Yamamoto, Takashi Yamanaka, Shinya Hotta, Akitsu https://orcid.org/0000-0002-2619-7441 (unconfirmed) |
著者名の別形: | 李, 紅梅 笹川, 典子 田中, 道廣 天野, 直己 櫻井, 英俊 山中, 伸弥 堀田, 秋津 |
発行日: | 13-Jan-2015 |
出版者: | Elsevier Inc. |
誌名: | Stem Cell Reports |
巻: | 4 |
号: | 1 |
開始ページ: | 143 |
終了ページ: | 154 |
抄録: | Duchenne muscular dystrophy (DMD) is a severe muscle-degenerative disease caused by a mutation in the dystrophin gene. Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined. Using a unique k-mer database, we systematically identified a unique target region that reduces off-target sites. To restore the dystrophin protein, we performed three correction methods (exon skipping, frameshifting, and exon knockin) in DMD-patient-derived iPSCs, and found that exon knockin was the most effective approach. We further investigated the genomic integrity by karyotyping, copy number variation array, and exome sequencing to identify clones with a minimal mutation load. Finally, we differentiated the corrected iPSCs toward skeletal muscle cells and successfully detected the expression of full-length dystrophin protein. These results provide an important framework for developing iPSC-based gene therapy for genetic disorders using programmable nucleases. |
記述: | iPS細胞を使った遺伝子修復に成功 --デュシェンヌ型筋ジストロフィーの変異遺伝子を修復--. 京都大学プレスリリース. 2014-11-27. |
著作権等: | © 2015 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
URI: | http://hdl.handle.net/2433/210241 |
DOI(出版社版): | 10.1016/j.stemcr.2014.10.013 |
PubMed ID: | 25434822 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2014-11-27 |
出現コレクション: | 学術雑誌掲載論文等 |
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