Lloyd Jonathan, Tran Claire H, Wadhwani Krishen, Cuba Samaniego Christian, Subramanian Hari K K, Franco Elisa
Bioengineering, University of California at Riverside , Riverside, California 92521, United States.
Mechanical Engineering, University of California at Riverside , Riverside, California 92521, United States.
ACS Synth Biol. 2018 Jan 19;7(1):30-37. doi: 10.1021/acssynbio.7b00277. Epub 2017 Nov 10.
Nucleic acid aptamers are an expandable toolkit of sensors and regulators. To employ aptamer regulators within nonequilibrium molecular networks, the aptamer-ligand interactions should be tunable over time, so that functions within a given system can be activated or suppressed on demand. This is accomplished through complementary sequences to aptamers, which achieve programmable aptamer-ligand dissociation by displacing the aptamer from the ligand. We demonstrate the effectiveness of our simple approach on light-up aptamers as well as on aptamers inhibiting viral RNA polymerases, dynamically controlling the functionality of the aptamer-ligand complex. Mathematical models allow us to obtain estimates for the aptamer displacement kinetics. Our results suggest that aptamers, paired with their complement, could be used to build dynamic nucleic acid networks with direct control over a variety of aptamer-controllable enzymes and their downstream pathways.
核酸适配体是一种可扩展的传感器和调节剂工具包。为了在非平衡分子网络中使用适配体调节剂，适配体与配体之间的相互作用应随时间可调，以便给定系统内的功能能够根据需要被激活或抑制。这是通过与适配体互补的序列来实现的，这些序列通过将适配体从配体上置换下来，实现可编程的适配体 - 配体解离。我们证明了我们这种简单方法在发光适配体以及抑制病毒RNA聚合酶的适配体上的有效性，能够动态控制适配体 - 配体复合物的功能。数学模型使我们能够获得适配体置换动力学的估计值。我们的结果表明，与它们的互补序列配对的适配体可用于构建动态核酸网络，直接控制各种适配体可控酶及其下游途径。
