Zhou Zhongqi, Chan Hau Yi, Lo Pik Kwan
Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong 999077, China.
Key Laboratory of Biochip Technology, Biotech and Health Care, Shenzhen Research Institute of City University of Hong Kong, Shenzhen 518057, China.
JACS Au. 2025 Jun 19;5(7):2953-2976. doi: 10.1021/jacsau.5c00524. eCollection 2025 Jul 28.
-nitrobenzyl (ONB) groups based photoremovable protecting groups (PPGs) stand out as significant photocleavage components in oligonucleotides, owing to their straightforward synthesis, easy incorporation, and compatibility with a broad array of functional groups. These ONB-modified nucleic acids have found widespread applications in the area of biomedicine. In this perspective, we delve into the progress and study of PPGs derived from ONB for accurately controlling nucleic acid functions using light. Various chemical approaches are explored for incorporating ONB-based PPGs in different parts of single-stranded nucleic acids, including nucleobases, backbones, riboses, and phosphate groups, along with their distinct impacts on nucleic acid hybridization. Additionally, we evaluate the benefits and constraints of these alterations. Promising strategies, such as the molecular engineering of existing ONB derivatives, the integration of established PPGs with appropriate two-photon light-absorbing antennas in a modular setup, and the coupling of ONB protective groups with upconversion nanomaterials to extend their cleavage wavelengths into longer spectra are outlined and discussed. Subsequently, we systematically explore the biological applications of these light-responsive nucleic acids as versatile tools, specifically for light-triggered gene editing and as foundational elements for constructing 3D DNA-based nanomaterials for drug delivery. By leveraging the versatile chemistry of ONB alongside diverse nucleic acid modification techniques, we aim to provide an up-to-date overview while outlining existing challenges and proposing solutions within this evolving field. This Perspective seeks to foster innovation in the design of light-responsive nucleic acids within DNA nanotechnology for biomedical applications, underscoring the ongoing pursuit of novelty in this field.
基于对硝基苄基（ONB）的光可去除保护基团（PPGs）作为寡核苷酸中重要的光裂解成分脱颖而出，这归因于它们合成简单、易于引入以及与多种官能团的兼容性。这些ONB修饰的核酸在生物医学领域有着广泛的应用。从这个角度出发，我们深入探讨了源自ONB的PPGs在利用光精确控制核酸功能方面的进展和研究。探索了各种化学方法将基于ONB的PPGs引入单链核酸的不同部位，包括核碱基、主链、核糖和磷酸基团，以及它们对核酸杂交的不同影响。此外，我们评估了这些改变的益处和限制。概述并讨论了一些有前景的策略，例如对现有ONB衍生物进行分子工程改造、在模块化设置中将成熟的PPGs与合适的双光子吸光天线整合，以及将ONB保护基团与上转换纳米材料偶联以将其裂解波长扩展到更长光谱。随后，我们系统地探索了这些光响应性核酸作为多功能工具的生物学应用，特别是用于光触发的基因编辑以及作为构建用于药物递送的基于3D DNA的纳米材料的基础元件。通过利用ONB的通用化学性质以及各种核酸修饰技术，我们旨在提供最新的综述，同时概述该不断发展领域中现有的挑战并提出解决方案。这一观点旨在促进DNA纳米技术中用于生物医学应用的光响应性核酸设计的创新，强调该领域对新颖性的持续追求。
