Engineering Entropy-Driven Reactions and Networks Catalyzed by DNA

TLDR

Artificial biochemical circuits could transform biological engineering, but incorporating signal amplification into nucleic‑acid-based designs has been challenging. The study proposes a design strategy enabling an input oligonucleotide to catalyze the release of an output oligonucleotide that can further catalyze other reactions. The reaction is driven by the configurational entropy of the released molecule, yielding a simple, fast, modular, composable, and robust amplifying circuit element. Several circuits were built and characterized, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics.

Abstract

Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics.