Work

Nucleic acid triplex stabilization through multimodal association

Year: 2026

Type: article

Abstract: Nucleic acid triplexes are crucial for gene regulation and biotechnology, yet their formation kinetics remain poorly understood. Here, we report that dangling ends from both the triplex-forming oligonucleotide (TFO) and the duplex dramatically enhance triplex stability by accelerating association rate constants. Creating a single-base-pair dangling end at either duplex terminus or generating a TFO dangling end by removing a terminal base pair or extending a base in TFO improves binding affinity and association kinetics over blunt ends. Internal locked nucleic acid modifications also enhance stability through faster association and slower dissociation. Notably, appending a Cy3 fluorophore as a dangling end in TFO outperforms natural bases, driving both faster association and slower dissociation. Our findings establish that optimal triplex design requires strategic terminal and internal optimization, supporting a multimodal association mechanism.

Source: Cell Reports Physical Science

DOI: 10.1016/j.xcrp.2026.103504

Authors: Fangyu Zhou, Yiran Liu, Zhiyu Shu, Wenjin Li, Yongqiang Wang, Gang Chen

Institutions: Chinese University of Hong Kong, Chinese University of Hong Kong, Shenzhen, Nanyang Technological University, Shenzhen University

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,620

Funders: Natural Science Foundation of Shenzhen City, National Natural Science Foundation of China, National Outstanding Youth Science Fund Project of National Natural Science Foundation of China