Modular DNA-origami-based nanoarrays enhanced cell binding-affinity through “lock-key” interaction

Abstract

Surface proteins of cells are generally recognized through receptor-ligand interactions (RLIs) in disease diagnosis, but their nonuniform spatial distribution and high-order structure lead to low binding-affinity. Constructing nano-topologies that match the spatial distribution of membrane proteins to improve binding-affinity remains a challenge. Inspired by the multi-antigen recognition of immune synapses, we developed modular DNA-origami-based nanoarrays with multivalent aptamers. By adjusting the valence and inter-spacing of the aptamers, we construct specific nano-topology to match the spatial distribution of target protein clusters and avoid potential steric hindrance. We found that the nanoarrays significantly enhanced the binding-affinity of target cells, and synergistically recognize low-affinity antigen-specific cells. In addition, using DNA nanoarrays for the detection of clinical circulation tumor cells successfully verified its precise recognition ability and high affinity RLIs. Such nanoarrays will further promote the potential application of DNA materials in clinical detection and even cell membrane engineering.

Engineering Circular Aptamer Assemblies with Tunable Selectivity to Cell Membrane Antigens In Vitro and In Vivo

“…DNA-based materials offer another platform for engineering highly controllable and addressable scaffolds and binding agents. − For instance, DNA nanotechnology allows for constructions of various nanostructures for precise modification of different binding agents. − System evolution of ligands by exponential enrichment (SELEX) technology facilitates the discovery of aptamer panels that can recognize a wide range of targets, especially the cell surface antigens. , In addition, it is generally believed that these pure DNA-based delivery platforms are with low immunogenicity and therefore have been explored as tools for targeted drug delivery in vivo . However, most reported DNA-based targeting platforms were focusing on improving the binding affinity by functionalizing multiple aptamers on the scaffolds. − Limited studies were reported to investigate the facets of avidity optimization such as tuning the binding selectivity based on antigen densities, ligand valency, and antigen/ligand affinity . Specifically, there is still lack of theoretical models and experimental data that elaborate the performance (i.e., affinity and specificity) of multivalent high/low-affinity interactions of DNA aptamers to their antigens on cell membranes in vitro and in vivo .…”