Brown Carl W, Lakin Matthew R, Horwitz Eli K, Fanning M Leigh, West Hannah E, Stefanovic Darko, Graves Steven W
Center for Biomedical Engineering, Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM 87131 (USA).
Angew Chem Int Ed Engl. 2014 Jul 7;53(28):7183-7. doi: 10.1002/anie.201402691. Epub 2014 Jun 2.
Signal propagation through enzyme cascades is a critical component of information processing in cellular systems. Although such systems have potential as biomolecular computing tools, rational design of synthetic protein networks remains infeasible. DNA strands with catalytic activity (DNAzymes) are an attractive alternative, enabling rational cascade design through predictable base-pair hybridization principles. Multi-layered DNAzyme signaling and logic cascades are now reported. Signaling between DNAzymes was achieved using a structured chimeric substrate (SCS) that releases a downstream activator after cleavage by an upstream DNAzyme. The SCS can be activated by various upstream DNAzymes, can be coupled to DNA strand-displacement devices, and is highly resistant to interference from background DNA. This work enables the rational design of synthetic DNAzyme regulatory networks, with potential applications in biomolecular computing, biodetection, and autonomous theranostics.
通过酶级联反应进行信号传播是细胞系统中信息处理的关键组成部分。尽管此类系统具有作为生物分子计算工具的潜力，但合成蛋白质网络的合理设计仍然不可行。具有催化活性的DNA链（DNAzyme）是一种有吸引力的替代方案，它能够通过可预测的碱基对杂交原理实现级联反应的合理设计。现在报道了多层DNAzyme信号传导和逻辑级联反应。DNAzyme之间的信号传导是通过一种结构化嵌合底物（SCS）实现的，该底物在被上游DNAzyme切割后会释放下游激活剂。SCS可以被各种上游DNAzyme激活，可以与DNA链置换装置耦合，并且对背景DNA的干扰具有高度抗性。这项工作实现了合成DNAzyme调控网络的合理设计，在生物分子计算、生物检测和自主治疗诊断方面具有潜在应用。
