Functional Nucleic Acids for Cell–Cell Interactions

Cell-cell interactions play an important role in maintaining tissue homeostasis and regulating physiological processes, involving direct contact, signal molecule transmission, vesicle-mediated communication, and other modes. A profound understanding and precise regulation of cell-cell interactions can help reveal cellular function mechanisms, guide tissue engineering, and promote the development of novel therapeutic strategies. In recent years, functional nucleic acids (FNAs) have become important tools for analyzing and regulating cell-cell interactions, owing to their excellent biocompatibility, structural programmability, and dynamic responsiveness. This review summarizes the progress of FNAs in cell-cell interactions, systematically sorts regulatory strategies of cell-cell interaction based on DNA hybridization, molecular recognition, scaffold construction, and response to environmental stimuli, and highlights their applications in cellular immunotherapy, cellular force monitoring, reconstruction of 3D tissue models in vitro, and cell-cell communication. Finally, current challenges and future development directions are discussed, aiming to provide new perspectives for advancing the application of FNAs in cell-cell interactions and precision medicine.