Citation: Kun Liu, Junjun Lu, Jincheng Lin, Yulin Cong, Xiongfeng Luo, Zihong Huang, Tianyi Zhang, Miao Wang, Zhiyong Xie, Hao Li. A transformable DNA Nano-windmill for the activation and regulation of the heterodimerization receptors across RTK families[J]. Chinese Chemical Letters, ;2026, 37(4): 111049. doi: 10.1016/j.cclet.2025.111049 shu

A transformable DNA Nano-windmill for the activation and regulation of the heterodimerization receptors across RTK families

Kun Liu ^{a, 1} ,
Junjun Lu ^{a, 1} ,
Jincheng Lin ^a ,
Yulin Cong ^a ,
Xiongfeng Luo ^a ,
Zihong Huang ^a ,
Tianyi Zhang ^c ,
Miao Wang ^{b, *,} ,
Zhiyong Xie ^{a, *,} ,
Hao Li ^{a, *,}

a.
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China
b.
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
c.
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China

wanger726@163.com

xiezhy@mail.sysu.edu.cn

lihao258@mail.sysu.edu.cn

Received Date: 24 December 2024
Revised Date: 5 March 2025
Accepted Date: 6 March 2025
Available Online: 7 March 2025

Figures(4)

Heterodimerization of receptor tyrosine kinases (RTKs) plays unique roles in cell signaling and functions. However, engineering heterodimerization of multiple receptors remains largely unexplored. Herein, we developed an aptamer-based DNA Nano-windmill (TA3) to regulate heterodimerization of three different RTK families, simultaneously activating fibroblast growth factor receptor 1 (FGFR1), hepatocyte growth factor receptor (Met) and epidermal growth factor receptor (EGFR) signaling. It is the first DNA Nano-windmill that activates heterodimerization of FGFR1, Met and EGFR, leading to the down-stream signals transduction, such as the phosphorylation of protein kinase B (Akt) and extracellular regulated protein kinases (Erk), inducing the cell migration and proliferation. We further designed transformable DNA Nano-windmill (TMA) that can convert DNA Nano-windmill into DNA Nano-kite using complementary strands or small molecules to reduce the activation of specific receptor. We believe that the DNA Nano-windmill for heterodimerization of different RTK families have potential applications in biomedicine fields.
- DNA Nano-windmill,
- Heterodimerization,
- Receptor tyrosine kinases,
- Aptamer,
- Cell regulation
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