細胞選択的ゲノム編集のための酵素誘導CRISPR/Cas9のオートホーナル化学活性化
Weiqi Cai1,2, Ji Liu1,2, Xianghan Chen1,2
1Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Journal of the American Chemical Society
|November 11, 2022
まとめ
精密なゲノム編集システムである 酵素誘導型CRISPR (eiCRISPR) を開発しました この新しいアプローチは,病気に関連した酵素を用いて,Cas9の活性を制御し,がん細胞の標的遺伝子治療を可能にします.
科学分野:
- バイオテクノロジー
- 分子生物学
- 遺伝子編集
背景:
- CRISPR/Cas9のゲノム編集の精度は,DNA分裂の制御によって制限されています.
- 制御可能で細胞選択的なゲノム編集システムの開発は 治療的な応用において極めて重要です
研究 の 目的:
- 条件付きで細胞選択的なゲノム編集システムである酵素誘導型CRISPR (eiCRISPR) を導入する.
- 癌細胞の精密なゲノム編集を可能にするために 病気に関連した酵素を活性化します
主な方法:
- eiCRISPRシステムは,Cas9タンパク質,自己阻害の不活性単一ガイドRNA (bsgRNA),および化学的にケージされたデオキシリボ酵素 (DNA酵素) を含む.
- DNA酵素活性は,腫瘍細胞過剰発現した酵素 (例えば,NQO1) によって回復し,bsgRNAとeiCRISPRを活性化する.
- 生物分解性脂質ナノ粒子は,腫瘍を伴う異種移植モデルにおいて,体内での投与に使用された.
主要な成果:
- 癌細胞における選択的ゲノム編集が,酵素誘発によるeiCRISPRの活性化によって実証されています.
- ヒトパピローマウイルス18E6を in vivoで成功裏に編集し,がん治療の可能性を示した.
- eiCRISPRを調節するためのポスト合成およびサイト固有のDNA酵素の改変を示した.
結論:
- eiCRISPRは 制御可能で細胞選択的な ゲノム編集のプラットフォームを提供します
- このシステムは特にがん治療において 標的型遺伝子療法に 期待されています
- この戦略は,内生化学を用いたゲノム編集の制御に適応可能である.
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