Analysis of cell signaling profiles induced by DNA aptamer-based FGFR1 agonist

DNA aptamers have attracted attention as an alternative modality for biomolecules due to their excellent target binding specificity and thermal stability, and they are also expected to be applied as artificial agonists for receptor proteins. DNA aptamer agonist TD0 targeting the receptor of fibroblast growth factor (FGFR), which plays an important role in the fields of wound healing and regenerative medicine, has been reported to induce cellular responses as well as its native ligands. However, it was also noted that there were some different responses upon long-term stimulation, suggesting that the intracellular signals induced by DNA aptamer agonist TD0 are different from those of natural ligands. In this paper, we comprehensively analyzed the intracellular signals induced by DNA aptamer agonist TD0 targeting FGFR1, and compared them with those by natural protein ligand FGF2. It was found that the intracellular signals were highly similar for short-term stimulation. On the other hand, the receptor and the downstream cellular signals showed different activation behaviors for long-time stimulation. Evaluating the stability and sustained activity of DNA aptamer agonist TD0 and FGF2 in the medium suggested that ligand stability may be important in properly regulating cellular responses.

Graphical Abstract