DNA switches are ideally suited for numerous nanotechnological applications, and increasing efforts are being directed toward their engineering. In this review, we discuss how to engineer these switches starting from the selection of a specific DNA-based recognition element, to its adaptation and optimisation into a switch, with applications ranging from sensing to drug delivery, smart materials, molecular transporters, logic gates and others. We provide many examples showcasing their high programmability and recent advances towards their real life applications. We conclude with a short perspective on this exciting emerging field.

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Hydrogen bonding is a key element in crystal engineering to direct crystal packing. Here, hydrogen bonding with molecular glasses is rather exploited to thwart crystallization.

Unlike artificial nanosystems, biological systems are ideally engineered to respond to their environment. As such, natural molecular buffers ensure precise and quantitative delivery of specific molecules through self-regulated mechanisms based on Le Chatelier’s principle. Here, we apply this principle to design self-regulated nucleic acid molecular buffers for the chemotherapeutic drug doxorubicin and the antimalarial agent quinine. We show that these aptamer-based buffers can be programmed to maintain any specific desired concentration of free drug both in vitro and in vivo and enable the optimization of the chemical stability, partition coefficient, pharmacokinetics and biodistribution of the drug. These programmable buffers can be built from any polymer and should improve patient therapeutic outcome by enhancing drug activity and minimizing adverse effects and dosage frequency.