How to program DNA like we do computers

Researchers program DNA molecules to follow specific instructions to create sophisticated molecular machines for medical and research uses
December 18, 2017

A programmable chemical oscillator made from DNA (credit: Ella Maru Studio and Cody Geary)

Researchers at The University of Texas at Austin have programmed DNA molecules to follow specific instructions to create sophisticated molecular machines that could be capable of communication, signal processing, problem-solving, decision-making, and control of motion in living cells — the kind of computation previously only possible with electronic circuits.

Future applications may include health care, advanced materials, and nanotechnology.

As a demonstration, the researchers constructed a first-of-its-kind chemical oscillator that uses only DNA components — no proteins, enzymes or other cellular components — to create a classic chemical reaction network (CRN) called a “rock-paper-scissors oscillator.” The goal was to show that DNA alone is capable of precise, complex behavior.

A systematic pipeline for programming DNA-only dynamical systems and the implementation of a chemical oscillator (credit: Niranjan Srinivas et al./Science)

Chemical oscillators have long been studied by engineers and scientists. For example, the researchers who discovered the chemical oscillator that controls the human circadian rhythm — responsible for our bodies’ day and night rhythm — earned the 2017 Nobel Prize in physiology or medicine.

“As engineers, we are very good at building sophisticated electronics, but biology uses complex chemical reactions inside cells to do many of the same kinds of things, like making decisions,” said David Soloveichik, an assistant professor in the Cockrell School’s Department of Electrical and Computer Engineering and senior author of a paper in the journal Science.

“Eventually, we want to be able to interact with the chemical circuits of a cell, or fix malfunctioning circuits or even reprogram them for greater control. But in the near term, our DNA circuits could be used to program the behavior of cell-free chemical systems that synthesize complex molecules, diagnose complex chemical signatures, and respond to their environments.”

The team’s research was conducted as part of the National Science Foundation’s (NSF) Molecular Programming Project and funded by the NSF, the Office of Naval Research, the National Institutes of Health, and the Gordon and Betty Moore Foundation.

Programming a Chemical Oscillator

Abstract of Enzyme-free nucleic acid dynamical systems

An important goal of synthetic biology is to create biochemical control systems with the desired characteristics from scratch. Srinivas et al. describe the creation of a biochemical oscillator that requires no enzymes or evolved components, but rather is implemented through DNA molecules designed to function in strand displacement cascades. Furthermore, they created a compiler that could translate a formal chemical reaction network into the necessary DNA sequences that could function together to provide a specified dynamic behavior.