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自然CRISPR-Cas12a阻害剤の体系的な発見

Kyle E Watters¹, Christof Fellmann^1,2, Hua B Bai¹

¹Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

Science (New York, N.Y.)

|September 8, 2018

まとめ

研究者らはヒト細胞におけるCRISPR-Cas12a遺伝子編集のための3つの新しい阻害剤を発見した. この発見は,CRISPR-Cas12a技術を制御し,より多くの微生物の抗CRISPRタンパク質を発見するための新しい道を開きます.

科学分野:

分子生物学
ゲノミクス
バイオテクノロジー

背景:

CRISPR-Cas12a (Cpf1) は,ゲノム工学で広く使用されている汎用的な核酶です.
CRISPR- Cas9 と Cas3 システムとは異なり,CRISPR- Cas12aに対する既知の阻害剤はこれまで発見されていなかった.
抑制剤の欠如は,CRISPR-Cas12aの適用に対する正確な制御を制限する.

研究の目的:

人体細胞におけるCRISPR- Cas12a活性の新しい阻害剤を特定する.
CRISPRの自己標的化と反CRISPRの流行の関係を探求する.

主な方法:

総合的な生物情報学と実験的なスクリーニングアプローチを採用しました.
CRISPR-Cas12a媒介によるゲノム編集を阻害または減少させる能力をテストした.
CRISPRの自己ターゲティングと反CRISPRの要素の関連性についてプロカリオットゲノムを分析した.

主要な成果:

人体細胞におけるCRISPR- Cas12a遺伝子編集を効果的に阻害または抑制する3つの異なる阻害剤を特定した.
CRISPRの自己標的化と抗CRISPRの存在との間に重要な相関が発見されました
これは多くの新しいアンチCRISPRを発見するための潜在的なメカニズムを示唆しています

結論:

CRISPR-Cas12a阻害剤の発見は精密なゲノム工学のための重要なツールを提供します
これらの発見は,様々な分野でCRISPR-Cas12aの制御性と安全性を高めています.
自己ターゲティングと阻害剤の流行の間の確認されたリンクは,将来の抗CRISPR発見のための有望な戦略を提供します.

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