Antibody Activation using DNA-Based Logic Gates†
We thank Dr. Tom de Greef for stimulating discussions. This work was supported by NanoNextNL, a micro- and nanotechnology consortium of the Government of the Netherlands and 130 partners, and by an ERC starting grant (ERC-2011-StG 280255).
Graphical Abstract
Logic antibody locks: Bivalent peptide–DNA conjugates are presented as generic, noncovalent, and easily applicable molecular locks that allow the control of antibody activity using toehold-mediated strand displacement. By connecting antibody-based molecular recognition and DNA-based computing, this new approach allows the introduction of autonomous signal-processing in antibody-based targeting.
Abstract
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.
