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Valence-programmable nucleic acid constructs targeting FGFR1 for promotion of tissue regeneration
Jieyu Wang1, Xue Wang1, Fang He1
1State Key Laboratory of Chemo and Biosensing, College of Chemistry and Chemical Engineering, College of Biology, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan, 410082, China. wanghonghui@hnu.edu.cn.
None:
We report a valence-programmable nucleic acid construct platform targeting FGFR1 (NACFs) comprising monovalent NACF-mono, Y-shaped NACF-Bi, and dendritic NACF-multi for engineering stable and efficient agonists. The bioactivity of NACFs exhibited strong valency-dependence, with the higher-valence NACF-multi demonstrating optimal performance. The dendritic construct promoted receptor oligomerization, enhanced serum stability, and elicited potent downstream signaling, thereby stimulating fibroblast proliferation and migration while accelerating tissue regeneration in vivo. This modular DNA-based agonist platform establishes valency engineering as a general strategy to tune receptor oligomerization and regenerative outcomes.
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