Antibody activation using DNA-based logic gates

Oligonucleotide-based molecular circuits offer the exciting possibility to introduce autonomous signal processing in biomedicine, synthetic biology, and molecular diagnostics. Here we introduce bivalent peptide–DNA conjugates as generic, noncovalent, and easily applicable molecular locks that allow the control of antibody activity using toehold-mediated strand displacement reactions. Employing yeast as a cellular model system, reversible control of antibody targeting is demonstrated with low nM concentrations of peptide–DNA locks and oligonucleotide displacer strands. Introduction of two different toehold strands on the peptide–DNA lock allowed signal integration of two different inputs, yielding logic OR- and AND-gates. The range of molecular inputs could be further extended to protein-based triggers by using protein-binding aptamers.