美国亚利桑那州立大学分子科学学院Alexander A. Green和Hao Yan课题组合作，利用超特异性核糖调控子精确和可编程地检测突变。相关论文于2020年2月27日发表在《细胞》杂志上。

他们报告了一类从头设计的原核生物核糖调控子，可在体内和无细胞转录-翻译反应中提供超特异的RNA检测功能。这些单核苷酸特异性可编程核糖调控子（SNIPR）响应大肠杆菌中单个核苷酸差异的靶RNA，在基因表达中提供100倍以上的差异，并在体外解析单个转录组标记。

利用可编程的SNIPR设计，他们实现了一种自动设计算法，以开发核糖调控子，用于与癌症、耐药性和遗传疾病相关的一系列突变。将SNIPR与便携式纸质无细胞反应相结合，可以方便地等温检测临床样品中与癌症相关的突变，并通过明确的比色反应鉴定Zika菌株。

据介绍，鉴定单核苷酸突变的能力对于探测细胞生物学和精确检测疾病至关重要。然而，单碱基改变所提供的杂交能量的微小差异，使得鉴定这些活细胞和复杂反应环境中的突变具有挑战性。

附：英文原文

Title: Precise and Programmable Detection of Mutations Using Ultraspecific Riboregulators

Author: Fan Hong, Duo Ma, Kaiyue Wu, Lida A. Mina, Rebecca C. Luiten, Yan Liu, Hao Yan, Alexander A. Green

Issue&Volume: 2020-02-27

Abstract: The ability to identify single-nucleotide mutations is critical for probing cell biology and for precise detection of disease. However, the small differences in hybridization energy provided by single-base changes makes identification of these mutations challenging in living cells and complex reaction environments. Here, we report a class of de novo-designed prokaryotic riboregulators that provide ultraspecific RNA detection capabilities in vivo and in cell-free transcription-translation reactions. These single-nucleotide-specific programmable riboregulators (SNIPRs) provide over 100-fold differences in gene expression in response to target RNAs differing by a single nucleotide in E. coli and resolve single epitranscriptomic marks in vitro. By exploiting the programmable SNIPR design, we implement an automated design algorithm to develop riboregulators for a range of mutations associated with cancer, drug resistance, and genetic disorders. Integrating SNIPRs with portable paper-based cell-free reactions enables convenient isothermal detection of cancer-associated mutations from clinical samples and identification of Zika strains through unambiguous colorimetric reactions.

DOI: 10.1016/j.cell.2020.02.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30155-0