High-Fidelity DNA Hybridization using Programmable Molecular DNA Devices

The hybridization of complementary nucleic acid strands is the most basic of all reactions involving nucleic acids, but has a major limitation: the specificity of hybridization reactions depends critically on the lengths of the complementary pairs of strands and can drop to very low values for sufficiently long strands. This reduction in specificity occurs especially in the presence of noise in the form of other competing strands that have sequence segments identical to the target. This limits the scale and accuracy of biotechnology and nanotechnology applications which depend on hybridization reactions. Our paper develops techniques for ensuring specific high-fidelity DNA hybridization reactions for target strands of arbitrary length. Our protocol is executed autonomously, without external mediation and driven by a series of conversions of single stranded DNA into duplex DNA that help overcome kinetic energy traps, similar to DNA walkers.