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論文
- タイトル
- タイトル（英）
- SpCas9-HF1 enhances accuracy of cell cycle-dependent genome editing by increasing HDR efficiency, and by reducing off-target effects and indel rates.
- 参照URL
- https://researchmap.jp/daisukematsumoto/published_papers/46299792
- 著者
- 著者（英）
- Daisuke Matsumoto,Erina Matsugi,Kanae Kishi,Yuto Inoue,Kiyomi Nigorikawa,Wataru Nomura
- 担当区分
- 概要
- 概要（英）
- In genome editing, it is important to avoid off-target mutations so as to reduce unexpected side effects, especially for therapeutic applications. Recently, several high-fidelity versions of SpCas9 have been developed to reduce off-target mutations. In addition to reducing off-target effects, highly efficient intended target gene correction is also essential to rescue protein functions that have been disrupted by single nucleotide polymorphisms. Homology-directed repair (HDR) corrects genes precisely using a DNA template. Our recent development of cell cycle-dependent genome editing has shown that regulation of Cas9 activation with an anti-CRISPR-Cdt1 fusion protein increases HDR efficiency and reduces off-target effects. In this study, to apply high-fidelity SpCas9 variants to cell cycle-dependent genome editing, we evaluated anti-CRISPR inhibition of high-fidelity SpCas9s. In addition, HDR efficiency of high-fidelity SpCas9s was addressed, identifying eSpCas9, SpCas9-HF1, and LZ3 Cas9 as promising candidates. Although eSpCas9 and LZ3 Cas9 showed decreased HDR efficiency in cell cycle-dependent genome editing, SpCas9-HF1 successfully achieved increased HDR efficiency and few off-target effects when co-expressed with an AcrIIA4-Cdt1 fusion.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Molecular therapy. Nucleic acids
- 巻
- 35
- 号
- 1
- 開始ページ
- 102124
- 終了ページ
- 102124
- 出版年月
- 2024年3月12日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1016/j.omtn.2024.102124
- 共同研究・競争的資金等の研究課題
研究者
松本 大亮
(マツモト ダイスケ)