可光裂解的邻硝基苄基保护的 DNA 结构及其应用,Chemical Reviews

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可光裂解的邻硝基苄基保护的 DNA 结构及其应用
Chemical Reviews ( IF 62.1 ) Pub Date : 2023-04-20 , DOI: 10.1021/acs.chemrev.3c00016
Michael P O'Hagan ₁ , Zhijuan Duan ₂ , Fujian Huang ₂ , Shay Laps ₁ , Jiantong Dong ₁ , Fan Xia ₂ , Itamar Willner ₁

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这篇综述文章介绍了光化学脱保护原位的机理和应用-硝基苄基 (ONB) 功能化核酸及其对 DNA 纳米技术和材料化学、生物化学和系统化学等不同研究领域的影响。讨论的具体主题包括 ONB 修饰核酸的合成、ONB 单元光化学脱保护所涉及的机制，以及调节光脱保护过程所需的照射波长的光物理和化学方法。介绍了激活 ONB 笼状纳米结构、ONB 保护的 DNAzyme 和适体框架的原理。具体来说，解决了使用 ONB 保护的核酸在单细胞水平上对细胞内 mRNA 进行光触发时空放大传感和成像，并控制转录机制，证明了 ONB 去保护核酸对蛋白质翻译和基因表达的时空沉默。此外，ONB 修饰核酸的光脱保护在控制材料特性和功能方面也有重要应用。这些是通过ONB核酸功能化脂质体的光触发融合作为细胞-细胞融合的模型、ONB核酸功能化载药脂质体与细胞的光刺激融合用于治疗应用以及ONB核酸的光刻图案化而引入的。修改接口。特别是，实现了对膜状界面刚度的光刻控制，以引导细胞图案化生长。此外，ONB功能化微胶囊可作为光响应载体来控制药物的释放，ONB 修饰的 DNA 折纸框架充当机械装置或刺激响应容器，用于运行 CRISPR-Cas9 系统等 DNA 机器。讨论了光保护 DNA 结构的未来挑战和潜在应用。

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Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications

This review article introduces mechanistic aspects and applications of photochemically deprotected ortho-nitrobenzyl (ONB)-functionalized nucleic acids and their impact on diverse research fields including DNA nanotechnology and materials chemistry, biological chemistry, and systems chemistry. Specific topics addressed include the synthesis of the ONB-modified nucleic acids, the mechanisms involved in the photochemical deprotection of the ONB units, and the photophysical and chemical means to tune the irradiation wavelength required for the photodeprotection process. Principles to activate ONB-caged nanostructures, ONB-protected DNAzymes and aptamer frameworks are introduced. Specifically, the use of ONB-protected nucleic acids for the phototriggered spatiotemporal amplified sensing and imaging of intracellular mRNAs at the single-cell level are addressed, and control over transcription machineries, protein translation and spatiotemporal silencing of gene expression by ONB-deprotected nucleic acids are demonstrated. In addition, photodeprotection of ONB-modified nucleic acids finds important applications in controlling material properties and functions. These are introduced by the phototriggered fusion of ONB nucleic acid functionalized liposomes as models for cell–cell fusion, the light-stimulated fusion of ONB nucleic acid functionalized drug-loaded liposomes with cells for therapeutic applications, and the photolithographic patterning of ONB nucleic acid-modified interfaces. Particularly, the photolithographic control of the stiffness of membrane-like interfaces for the guided patterned growth of cells is realized. Moreover, ONB-functionalized microcapsules act as light-responsive carriers for the controlled release of drugs, and ONB-modified DNA origami frameworks act as mechanical devices or stimuli-responsive containments for the operation of DNA machineries such as the CRISPR-Cas9 system. The future challenges and potential applications of photoprotected DNA structures are discussed.

更新日期：2023-04-20

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