DNA-based AND logic gate as a molecular precision tool: selective recognition of protein pairs in lipid nanodiscs and subsequent binding of gold nanorods

The specificity of target recognition is paramount in fields such as cellular biology, diagnostics, and therapy. Traditional antibody-based methods focus on recognizing single antigens; however, the next level of specificity involves targeting pairs of antigens simultaneously. This study introduces a DNA-based molecular logic AND gate designed to recognize the two membrane proteins PD-L1 and CD3 as antigens via the corresponding antibody-oligonucleotide conjugates. The two membrane proteins are embedded in lipid nanodiscs that serve as a model system for cell membranes. By utilizing antibody-oligonucleotide conjugates as input signals, the DNA logic gate operates sequentially, becoming fully activated only upon binding both target proteins. The output signal facilitates subsequent actions, such as target isolation via magnetic bead extraction and functionalization with DNA-tagged gold nanorods for potential photothermal therapy. Our proof of concept for a molecular precision tool that processes two input signals in an AND operation and converts them to an output signal offers new avenues for high-specificity diagnostics and therapeutic interventions.