Harnessing DNA Nanotechnology for Nongenetic Manipulation and Functionalization of Cell Surface Receptor

Cell surface receptor oligomerization-mediated signal activation is a fundamental molecular mechanism governing cell behavior, with broad implications across a wide spectrum of health and disease contexts. The exploration of the biophysical principles underpinning cell receptor signaling and activation has been a major focus in biological research, paving the way for the development of molecular tools for the rational functionalization of receptors to synthetically modulate cell signaling. Over the past few decades, DNA nanotechnology has emerged as a highly designable, structurally predictable, and programmable methodology that allows for the precise construction of a variety of molecular recognition modules, spatial scaffold modules, and dynamic assembly modules. These advantageous features enable precise manipulation and activation of cell surface receptors for diverse functionalities, offering versatile and highly tailored approaches enabling non-genetical regulation of cells. This review outlines the recent advancements in the use of DNA nanotechnology for spatiotemporal manipulation of receptors and cell function reprogramming. Finally, we discuss the potential and challenges of DNA-based receptor engineering, especially for its future applications in regenerative medicine and cell-based therapy.