Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
ACS Nano. 2022 Apr 26;16(4):6153-6164. doi: 10.1021/acsnano.1c11631. Epub 2022 Mar 16.
The dynamic transient formation and depletion of G-quadruplexes regulate gene replication and transcription. This process was found to be related to various diseases such as cancer and premature aging. We report on the engineering of nucleic acid modules revealing dynamic, transient assembly and disassembly of G-quadruplex structures and G-quadruplex-based DNAzymes, gated transient processes, and cascaded dynamic transient reactions that involve G-quadruplex and DNAzyme structures. The dynamic transient processes are driven by functional DNA reaction modules activated by a fuel strand and guided toward dissipative operation by a nicking enzyme (Nt.BbvCI). The dynamic networks were further characterized by computational simulation of the experiments using kinetic models, allowing us to predict the dynamic performance of the networks under different auxiliary conditions applied to the systems. The systems reported herein could provide functional DNA machineries for the spatiotemporal control of G-quadruplex structures perturbing gene expression and thus provide a therapeutic means for related emergent diseases.
动态瞬态形成和消耗 G-四链体调节基因复制和转录。这一过程与癌症和早衰等各种疾病有关。我们报告了核酸模块的工程，揭示了 G-四链体结构和 G-四链体 DNA 酶的动态、瞬态组装和拆卸、门控瞬态过程以及涉及 G-四链体和 DNA 酶结构的级联动态瞬态反应。动态瞬态过程由受燃料链激活的功能 DNA 反应模块驱动，并通过切口酶（Nt.BbvCI）引导朝着耗散操作进行。通过使用动力学模型对实验进行计算模拟，进一步对动态网络进行了表征，使我们能够预测在施加于系统的不同辅助条件下网络的动态性能。本文报道的系统可以为 G-四链体结构的时空控制提供功能 DNA 机械装置，从而为相关新兴疾病提供治疗手段。
