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从多重菌体显示库中准SARS-CoV-2编程的核糖体框架转移RNA的循环酸

Jacob A Iannuzzelli¹, Rachel Bonn^2,3, Andrew S Hong¹

¹Department of Chemistry, University of Rochester Rochester NY 14627 USA.

Chemical science

|November 21, 2024

概括

研究人员开发了一种使用菌体显示的新方法,以创建可以与特定RNA结构结合的宏环,如SARS-CoV-2框架转移刺激序列 (FSS) RNA伪结,提供潜在的治疗策略.

科学领域:

化学生物学化学生物学
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

RNA的三级结构为类似药物的分子提供结合点.
针对具有高亲和度,特定分子的RNA是一个重大挑战.
像其他病毒一样,SARS-CoV-2依赖于RNA作为其遗传物质.

研究的目的:

开发一种用于发现和选择RNA向性宏环的新策略.
创建大型,结构多样化的遗传编码宏循环库.
识别特定的宏环,与SARS-CoV-2 FSS RNA伪结结合,具有很高的亲和力和选择性.

主要方法:

使用菌体显示平台对宏循环有机杂交物 (MOrPH-PhD).
采用了各种非正规的氨基酸基循环模块来生成10^7大循环的库.
面对SARS-CoV-2 FSS RNA伪结的图书馆进行了面试.

主要成果:

确定了具有高亲和力和对RNA的选择性的特定宏环序列.
确定结合局限于FSS二元化循环.
循环对目标RNA的特异性比无关的RNA伪结的特异性被证明.

结论:

引入了一种新的系统 (多重复合的MORPH-PhD) 用于生成和选拓上多样化的环酸支架.
提供了进化基因编码的宏环针对特定RNA标的蓝图.
突出了宏环类的潜力,作为对抗像SARS-CoV-2这样的RNA病毒的治疗剂.

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