Thermo-programmed synthetic DNA-based receptors

Here we present a generalizable and versatile strategy to rationally design synthetic DNA ligand-binding devices that can be programmed to load and release a ligand over a specific temperature range. We do so by re-engineering two model DNA-based receptors: a triplex forming bivalent DNA-based receptor that recognizes a specific DNA sequence and an ATP-binding aptamer. The temperature at which these receptors load/release their ligands can be finely modulated by controlling the entropy associated with the linker connecting the two ligand-binding domains. Through a thermodynamic characterization we demonstrate that this approach is highly programmable and allows to modulate the load/release temperature of the DNA receptors over a wide range of temperatures. By combining in the same solution a set of receptors with tunable and reversible temperature dependence we can also achieve complex load/release behavior such as sustained ligand release or loading at different temperatures. Similar programmable thermo-responsive synthetic ligand-binding devices can be of utility in applications such as drug delivery and production of smart materials.