核糖开关
合理设计
计算生物学
基因表达
计算机科学
基因
生物
合成生物学
基因表达调控
细胞生物学
遗传学
非编码RNA
作者
Guocai Zhong,Haimin Wang,Charles C. Bailey,Guangping Gao,Michael Farzan
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2016-11-02
卷期号:5
被引量:62
摘要
Efforts to control mammalian gene expression with ligand-responsive riboswitches have been hindered by lack of a general method for generating efficient switches in mammalian systems. Here we describe a rational-design approach that enables rapid development of efficient cis-acting aptazyme riboswitches. We identified communication-module characteristics associated with aptazyme functionality through analysis of a 32-aptazyme test panel. We then developed a scoring system that predicts an aptazymes’s activity by integrating three characteristics of communication-module bases: hydrogen bonding, base stacking, and distance to the enzymatic core. We validated the power and generality of this approach by designing aptazymes responsive to three distinct ligands, each with markedly wider dynamic ranges than any previously reported. These aptayzmes efficiently regulated adeno-associated virus (AAV)-vectored transgene expression in cultured mammalian cells and mice, highlighting one application of these broadly usable regulatory switches. Our approach enables efficient, protein-independent control of gene expression by a range of small molecules.
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