Li Huanhuan, Jin Zelong, Gao Shuxin, Kuang Shi, Lei Chunyang, Nie Zhou
State Key Laboratory of Chemo and Biosensing, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University Changsha 410082 People's Republic of China
Chem Sci. 2025 May 16. doi: 10.1039/d5sc00918a.
G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures that play a crucial role in regulating essential cellular processes such as replication, transcription, and translation. The formation of G4s is dynamically controlled by the physiological state of the cell. Accurate detection of G4 structures in live cells, as well as studies of their dynamic changes and the kinetics of specific G4s, are essential for understanding their biological roles, exploring potential links between aberrant G4 expression and disease, and developing G4-targeted diagnostic and therapeutic strategies. This perspective briefly overviews G4 formation mechanisms and their known biological functions. We then summarize the leading techniques and methodologies available for G4 detection, discussing the principles and applications of each approach. In addition, we outline strategies for the global detection of intracellular G4s, methods for conformational recognition, and approaches for targeting specific sequences. Finally, we discuss the technical limitations and challenges currently facing the field of G4 detection and offer perspectives on potential future directions. We hope this review will inspire further research into the biological functions of G4s and their applications in disease diagnosis and therapy.
G-四链体（G4s）是非经典核酸二级结构，在调控复制、转录和翻译等重要细胞过程中发挥关键作用。G4s的形成受细胞生理状态动态调控。在活细胞中准确检测G4结构，以及研究其动态变化和特定G4s的动力学，对于理解其生物学作用、探索异常G4表达与疾病之间的潜在联系以及开发针对G4的诊断和治疗策略至关重要。本文简要概述了G4的形成机制及其已知的生物学功能。然后，我们总结了用于G4检测的主要技术和方法，讨论了每种方法的原理和应用。此外，我们概述了细胞内G4s的全局检测策略、构象识别方法以及靶向特定序列的方法。最后，我们讨论了G4检测领域目前面临的技术局限性和挑战，并对潜在的未来方向提出了展望。我们希望这篇综述能激发对G4s生物学功能及其在疾病诊断和治疗中应用的进一步研究。
