封装自身RNA基因组的设计蛋白组件的演变
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
概括
科学家们从非病毒蛋白质中制造出合成核体,能够有效地包装和保护遗传物质. 这些新型蛋白质组合具有类似病毒的特性,用于潜在的生物医学应用.
科学领域:
- 生物技术
- 合成生物学
- 蛋白质工程
背景情况:
- 生物系统使用封装来保护遗传物质,病毒使用体.
- 由于对效率而不是模块化的进化优化,工程病毒囊具有挑战性.
- 合成蛋白质组件为开发无病毒安全问题的生物医疗工具提供了"白板".
研究的目的:
- 为高效的基因组包装和保护创造和发展合成核体.
- 探索用于药物输送和生物医学应用的计算设计蛋白质组件的潜力.
- 通过计算设计和定向进化来展示一种"自下而上"的方法来创造功能性纳米材料.
主要方法:
- 具有正电荷的内部表面的计算设计的二面体蛋白组件.
- 能够包装自己的全长mRNA基因组的合成核体.
- 使用大肠杆菌的定向进化来优化核体特性.
主要成果:
- 在基因组包装效率上实现了133倍以上的改善.
- 在血液中提高稳定性,在6小时后保护包装的RNA从不到3. 7%到7%.
- 血液循环时间从不到5分钟增加到大约4. 5小时.
- 每11个组件中一个全长RNA基因组的包装,可与腺相关病毒载体相比较.
结论:
- 合成蛋白质组件可以发展出类似病毒的基因组包装和保护能力.
- 计算设计的蛋白质组合的定向进化提供了一个可编程的"自下而上的"替代修改病毒.
- 这些合成核体显示出药物输送和其他生物医学应用的前景.
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