基于核酶的人工DNA回路系统构建及分析

近年来，基因调控机制研究在生物医药和疾病诊疗领域产生了革命性的影响。但由于基因网络和细胞微环境高度复杂，使得体外调控与胞内基因网络系统难以衔接。本世纪初，新型人工DNA回路系统发展迅速，有望突破“体外-胞内生物系统联通屏障”的限制。本项目拟结合分子自组装，构建自变构核酶DNA人工逻辑回路，以实现基因分子网络精细调控、信号检测和分子智能系统控制。重点围绕DNAzyme逻辑分子回路、分子逻辑单元和神经网络等多个前沿交叉领域，对自变构核酶人工DNA逻辑回路系统展开多角度的研究。首先，围绕DNA编码，利用分子编程设计，筛选优化回路所需DNA序列。其次，基于DNAzyme的分子逻辑单元，研究单元接口的兼容性和可连通性。最后，结合多种单分子检测手段，实现多层级联DNA回路和分子神经网络回路的构建。项目聚焦DNA智能分子系统等前沿领域，研究成果在信息和材料等领域具有广泛的潜在应用。

In recent years, the gene regulatory mechanism has had a revolutionary impact in the field of biomedicine and disease diagnosis and treatment. However, due to the complexity of gene network and cell microenvironment, it is difficult to connect the in vitro regulation with the in cell gene network system. At the beginning of this century, the novel artificial DNA circuits has been rapidly developed, which is expected to break through the limitation of "in vitro intracellular biological system connection barrier". In this project, we plan to combine molecular self-assembly to build an artificial DNAzyme logic circuit to realize the regulation of gene molecular network, signal detection and molecular intelligent system control. This project focuses on the research of the DNAzyme logic circuit system, combining DNAzyme logic molecular circuit, molecular logic unit and neural network. First, using molecular programming design, DNA sequences required in the circuit are screened and optimized. Second, based on the molecular logic unit of DNAzyme, the compatibility and connectivity of unit interface are studied. Finally, combining with a variety of single molecule detection methods, the construction of multi-layer cascade DNA circuit and molecular neural network circuit is realized. The project focuses on the frontier fields such as DNA intelligent molecular system, and the results have a wide range of potential applications in the fields of information and materials.