Zou Kexuan, Zhang Pengfei, Wang Yuqi, Liu Yan, Ji Bin, Zhan Pengfei, Song Jie
Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Small Methods. 2024 Sep 5:e2401041. doi: 10.1002/smtd.202401041.
DNA nanostructures have shown great potential in biomedical fields. However, the immune responses, especially the activation of the cGAS-STING signaling (A-cGSs), induced by DNA nanostructures, remain incompletely understood. Here, the ability of various DNA nanostructures from double-stranded DNA (dsDNA), single-stranded tiles (SSTs) to DNA origami is investigated on A-cGSs. Unlike natural dsDNA which triggers potent A-cGSs, the structural interconnectivity of various DNA configurations can substantially reduce the occurrence of A-cGSs, irrespective of their form, dimensions, and conformation. However, wireframe DNA nanostructures can activate the cGAS-STING signaling, suggesting that decreasing A-cGSs is dsDNA compactness-dependent. Based on this, a reconfigurable DNA Origami Domino Array (DODA) is used to systematically interrogate how dsDNA influences the A-cGSs and demonstrates that the length, number, and space of dsDNA array coordinately influence the activation level of cGAS-STING signaling, realizing a regulation of innate immune response. The above data and findings enhance the understanding of how DNA nanostructures affect cellular innate immune responses and new insights into the modulation of innate immune responses by DNA nanomedicine.
DNA纳米结构在生物医学领域已显示出巨大潜力。然而，DNA纳米结构诱导的免疫反应，尤其是cGAS-STING信号通路的激活（A-cGSs），仍未被完全理解。在此，研究了从双链DNA（dsDNA）、单链片（SSTs）到DNA折纸等各种DNA纳米结构对A-cGSs的影响。与触发强烈A-cGSs的天然dsDNA不同，各种DNA构型的结构互连性可大幅降低A-cGSs的发生，无论其形式、尺寸和构象如何。然而，框架DNA纳米结构可激活cGAS-STING信号通路，这表明降低A-cGSs依赖于dsDNA的紧密性。基于此，使用可重构DNA折纸多米诺阵列（DODA）系统地探究dsDNA如何影响A-cGSs，并证明dsDNA阵列的长度、数量和间距协同影响cGAS-STING信号通路的激活水平，实现了对先天免疫反应的调控。上述数据和发现增进了对DNA纳米结构如何影响细胞先天免疫反应的理解，并为DNA纳米医学对先天免疫反应的调节提供了新见解。
