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独自のRNAゲノムをカプセル化した設計されたタンパク質組成の進化
Gabriel L Butterfield1,2,3, Marc J Lajoie1,2, Heather H Gustafson4,5
1Institute for Protein Design, University of Washington, Seattle, Washington 98195, USA.
Nature
|December 14, 2017
まとめ
科学者は非ウイルス性タンパク質から 合成核カプシドを設計し 遺伝物質を効率的に包装し 保護することができました これらの新種のタンパク質は 生物医学的な応用のために ウイルスのような特性を進化させました
科学分野:
- バイオテクノロジー
- 合成生物学
- タンパク質工学
背景:
- 生物系では遺伝物質の保護のためにカプセル化が用いられ,ウイルスではカプシドが用いられる.
- ウイルスカプシドの設計は,モジュラリティに対する効率の進化的最適化により困難です.
- 合成タンパク質の組み立ては ウイルスの安全性に関する懸念なしに バイオメディカルツールの開発のための"空白のスレート"を提供する.
研究 の 目的:
- 効率的なゲノム包装と保護のための合成核カプシドを作成し,進化させる.
- 薬剤の配達と生物医学的な応用のための計算式設計されたタンパク質アセンブリの可能性を探求する.
- コンピューティングデザインとダイレクトされた進化を通じて機能的なナノマテリアルを作成するための"ボトムアップ"アプローチを実証する.
主な方法:
- 計算で設計された,正電荷の内部表面を持つイコサヘドラルなタンパク質組.
- 自らの全長mRNAゲノムを包装できる合成核カプシドを設計した.
- 核カプシドの特性を最適化するために,Escherichia coliの指向進化を利用した.
主要な成果:
- ゲノム包装の効率を 133倍以上改善しました
- 血液の安定性を高め,包装RNAを6時間後に3. 7%未満から71%まで保護します.
- 血液循環時間は5分未満から約4. 5時間に増加しました.
- アデノ関連ウイルスのベクトルに匹敵する11つのアセンブリごとに1つの完全なRNAゲノムの包装が実証されています.
結論:
- 合成タンパク質は ウイルスのようなゲノム包装と 保護能力を進化させることができます
- コンピュータで設計されたタンパク質アセンブリの 誘導進化は,ウイルスを改変する上で プログラム可能な"下から上へ"の代替手段を提供する.
- これらの合成ヌクレオカプシドは 薬物投与やその他の生物医学的な応用に 期待されています
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