Valence-programmable nucleic acid constructs targeting FGFR1 for promotion of tissue regeneration

Abstract

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.