Exquisite sequence selectivity with small conditional RNAs.
Exquisite sequence selectivity with small conditional RNAs.
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DOI：
10.1021/nl501593r
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发表时间：
2014-08-13
期刊：
影响因子：
10.8
通讯作者：
Pierce NA
中科院分区：
文献类型：
--
作者：
Sternberg JB;Pierce NA
动态RNA纳米技术的基础上可编程的杂交级联与小的条件RNA（scRNA）提供了一个有前途的概念框架工程可编程的条件调控在体内。虽然单碱基取代（SBS）体细胞突变和单核苷酸多态性（SNP）是重要的标志物和疾病的驱动因素，但尚不清楚合成RNA信号转导子是否足够可编程以接受同源RNA输入，同时拒绝单核苷酸序列变体。在这里，我们探索了scRNA可编程性的限制，证明了RNA SBS癌症标志物和SNP的等温，无酶基因分型，使用scRNA在同源RNA靶标存在下执行条件杂交级联。动力学辨别可以在从几分钟到几天的时间尺度上进行设计。为了区分即使是最具挑战性的单核苷酸序列变体，包括那些导致几乎等能量的RNA摆动对的变体，用非结构化的清道夫链或其他scRNA进行竞争性抑制提供了实现精确序列选择性的简单而有效的原理。
Dynamic RNA nanotechnology based on programmable hybridization cascades with small conditional RNAs (scRNAs) offers a promising conceptual framework for engineering programmable conditional regulation in vivo. While single-base substitution (SBS) somatic mutations and single-nucleotide polymorphisms (SNPs) are important markers and drivers of disease, it is unclear whether synthetic RNA signal transducers are sufficiently programmable to accept a cognate RNA input while rejecting single-nucleotide sequence variants. Here, we explore the limits of scRNA programmability, demonstrating isothermal, enzyme-free genotyping of RNA SBS cancer markers and SNPs using scRNAs that execute a conditional hybridization cascade in the presence of a cognate RNA target. Kinetic discrimination can be engineered on a time scale of choice from minutes to days. To discriminate even the most challenging single-nucleotide sequence variants, including those that lead to nearly isoenergetic RNA wobble pairs, competitive inhibition with an unstructured scavenger strand or with other scRNAs provides a simple and effective principle for achieving exquisite sequence selectivity.
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影响因子：
10.2
作者：
Veigas B;Pedrosa P;Couto I;Viveiros M;Baptista PV
通讯作者：
Baptista PV
DOI：
10.1073/pnas.0407024101
发表时间：
2004-10-26
影响因子：
11.1
作者：
Dirks, RM;Pierce, NA
通讯作者：
Pierce, NA
影响因子：
46.9
作者：
通讯作者：
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影响因子：
16
作者：
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通讯作者：
Smolke CD
影响因子：
18.3
作者：
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通讯作者：
Ellington, Andrew D.