二重鎖断裂やドナーDNAなしの検索・置き換えゲノム編集
Andrew V Anzalone1,2,3, Peyton B Randolph1,2,3, Jessie R Davis1,2,3
1Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Nature
|October 22, 2019
まとめ
プライムエディティングは DNAを直接書き込むことで 遺伝疾患を正確に修正する 新しいゲノムエディティング技術です この多用途なツールは ほとんどの病気を引き起こす変種を 高い効率と少ない副産物で治すことができます
科学分野:
- 分子生物学
- 遺伝学
- バイオテクノロジー
背景:
- 遺伝子変異は 副産物なしで 効率的に修正するのは困難です
- 既存のゲノム編集方法には 精度と範囲の限界があります
研究 の 目的:
- 汎用的で正確な ゲノム編集方法を説明します
- ヒト細胞の遺伝子変異を 修正するプライム・エディティングの 能力を示すためだ
主な方法:
- プライム・エディティングは,リバース・トランスクリプトーゼと融合した,触媒的に障害のあるCas9を使用します.
- プライムエディティングガイドRNA (pegRNA) は,特定のDNAサイトを標的にし,編集をエンコードするシステムをプログラムします.
- 人間の細胞で175以上の編集を行いました 挿入,削除,そして12の点変異タイプも含みます
主要な成果:
- 状細胞病とタイ・サックス病の 遺伝的原因を正しました
- 保護トランスバーションをPRNPに設置し タグ/エピトープを正確に挿入しました
- プライムエディティングはホモロジー・ディレクテッド・リペアよりも高い効率と少ない副産物を示した.
- 標準のCas9ヌクレアースと比較して,より低いオフターゲットの編集を示した.
結論:
- プライムエディティングは ゲノムエディティングの機能を拡張します
- この方法は 病気に関連した遺伝子変異の89%まで 修正できる可能性があります
- 遺伝子疾患の修正には 精密で多岐にわたるアプローチを 提供しています
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