Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
Gene Ther. 2009 Oct;16(10):1189-201. doi: 10.1038/gt.2009.81. Epub 2009 Jul 9.
In the last two decades, remarkable advances have been made in the development of technologies used to engineer new aptamers and ribozymes. This has encouraged interest among researchers who seek to create new types of gene-control systems that can be made to respond specifically to small-molecule signals. Validation of the fact that RNA molecules can exhibit the characteristics needed to serve as precision genetic switches has come from the discovery of numerous classes of natural ligand-sensing RNAs called riboswitches. Although a great deal of progress has been made toward engineering useful designer riboswitches, considerable advances are needed before the performance characteristics of these RNAs match those of protein systems that have been co-opted to regulate gene expression. In this review, we will evaluate the potential for engineered RNAs to regulate gene expression and lay out possible paths to designer riboswitches based on currently available technologies. Furthermore, we will discuss some technical advances that would empower RNA engineers who seek to make routine the production of designer riboswitches that can function in eukaryotes.
在过去的二十年中，用于工程化新型适体和核酶的技术取得了显著的进展。这激发了研究人员的兴趣，他们寻求创建新型基因控制系统，使其能够专门响应小分子信号。RNA 分子可以表现出作为精确遗传开关所需的特征这一事实得到了大量被称为核酶的天然配体感应 RNA 类别的发现的验证。尽管在工程化有用的设计型核酶方面已经取得了很大的进展，但在这些 RNA 的性能特征与被用来调节基因表达的蛋白质系统相匹配之前，还需要取得相当大的进展。在这篇综述中，我们将评估工程化 RNA 调节基因表达的潜力，并根据当前可用的技术为设计型核酶制定可能的途径。此外，我们将讨论一些技术进步，这些进步将赋予那些寻求常规生产能够在真核生物中发挥作用的设计型核酶的 RNA 工程师权力。
