CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, 11 ZhongGuanCun BeiYiTiao, Beijing, 100190, China.
School of Chemistry and Biological Engineering, Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, 30 XueYuan Road, Beijing, 100083, China.
Angew Chem Int Ed Engl. 2024 Apr 24;63(18):e202404064. doi: 10.1002/anie.202404064. Epub 2024 Mar 22.
DNAzymes exhibit tremendous application potentials in the field of biosensing and gene regulation due to its unique catalytic function. However, spatiotemporally controlled regulation of DNAzyme activity remains a daunting challenge, which may cause nonspecific signal leakage or gene silencing of the catalytic systems. Here, we report a photochemical approach via modular weaving active DNAzyme into the skeleton of tetrahedral DNA nanocages (TDN) for light-triggered on-demand liberation of DNAzyme and thus conditional control of gene regulation activity. We demonstrate that the direct encoding of DNAzyme in TDN could improve the biostability of DNAzyme and ensure the delivery efficiency, comparing with the conventional surface anchoring strategy. Furthermore, the molecular weaving of the DNA nanostructures allows remote control of DNAzyme-mediated gene regulation with high spatiotemporal precision of light. In addition, we demonstrate that the approach is applicable for controlled regulation of the gene editing functions of other functional nucleic acids.
DNA zyme 由于其独特的催化功能，在生物传感和基因调控领域表现出巨大的应用潜力。然而，DNAzyme 活性的时空控制调节仍然是一个艰巨的挑战，这可能导致催化系统的非特异性信号泄漏或基因沉默。在这里，我们通过将活性 DNAzyme 模块化编织到四面体 DNA 纳米笼（TDN）的骨架中，报告了一种光化学方法，用于光触发按需释放 DNAzyme，从而实现对基因调控活性的条件控制。我们证明了 DNAzyme 在 TDN 中的直接编码可以提高 DNAzyme 的生物稳定性，并确保与传统的表面锚定策略相比，提高输送效率。此外，DNA 纳米结构的分子编织允许用光的高时空精度远程控制 DNAzyme 介导的基因调控。此外，我们证明该方法适用于其他功能核酸的基因编辑功能的控制调节。
