Protein–Protein Communication Mediated by an Antibody‐Responsive DNA Nanodevice**

Abstract

We report here the rational design and optimization of an antibody-responsive, DNA-based device that enables communication between pairs of otherwise non-interacting proteins. The device is designed to recognize and bind a specific antibody and, in response, undergo a conformational change that leads to the release of a DNA strand, termed the "translator," that regulates the activity of a downstream target protein. As proof of principle, we demonstrate antibodyinduced control of the proteins thrombin and Taq DNA polymerase. The resulting strategy is versatile and, in principle, can be easily adapted to control protein-protein communication in artificial regulatory networks.The complex, tightly regulated networks [1,2] through which DNA, RNA and proteins interact underly the functioning of living systems. [3][4][5] One of the aims of synthetic biology is to create artificial pathways in which DNA, RNA and proteins interact with each other via analogously "programmed" reaction patterns to create new tools for sensing, drugdelivery, cell imaging. [6][7][8][9][10][11][12][13][14] A widely used approach to this end is the rational design of synthetic DNA/protein communication that takes advantage of the many naturally occurring proteins that recognize and bind specific oligonucleotide sequences to, for example, regulate transcription or translation. [15][16][17][18][19][20][21] Such sequence-specific recognition has been employed in synthetic systems to regulate the load/release of molecular cargos from DNA-based devices, [22] the assembly/ disassembly of DNA-based structures [23] and DNA-based reactions. [24]

Erasable and Field Programmable DNA Circuits Based on Configurable Logic Blocks

“…However, we envision that in the future, by connecting their upstream with DNA aptamer‐based “biological interface” circuits, proteins and other biomacromolecules could participate in the operation and logical switching of CLB circuits. [ 52 , 53 , 54 ] This will significantly enhance the capability of DNA circuits to perform biological signal recognition and computation within the body, bringing them closer to the ultimate goal of a biological computer. Overall, the computing potential and multiple regulatory methods endow the CLB‐based DNA circuit with a wide range of application prospects.…”

A nicking enzyme-assisted allosteric strategy for self-resetting DNA switching circuits

“…In the future design, we will continue our research based on the reusability and parallel information processing capability of self-resetting DNA switching circuits to explore multi-signal detection technologies in actual biological samples. In addition, we will further combine the selective function of self-resetting DNA switches with selfassembled structures 47,48 and macromolecular proteins such as antibodies 49,50 to provide programmable tools for building intelligent nanomachines, highly specific drug delivery systems, and multi-signal detection and reusable biosensors.…”

Biomolecule-Driven Two-Factor Authentication Strategy for Access Control of Molecular Devices

“…For example, the number of roles is limited by the overlap of emission and excitation spectra of the fluorophores, the potential impact of temperature-induced DNA degradation on future applications, and the further enrichment of authentication factor types. In the future, we plan to make full use of the high programmability and addressability of DNA sequences that lead to deeper exploration processes in time and space; , to explore ways to characterize DNA molecules with multiple signals, allowing the number of roles to be independent of the fluorescence spectrum and enhancing the quality of deception defense strategy; to investigate silica-based DNA encapsulation technology, , making molecular devices immune to temperature; to combine pH, , light, , aptamers, , and antibodies − to further enrich the authentication factor library, thus improving the overall security of the molecular device.…”