Abstractions for DNA circuit design

Abstract

DNA strand displacement techniques have been used to implement a broad range of information processing devices, from logic gates, to chemical reaction networks, to architectures for universal computation. Strand displacement techniques enable computational devices to be implemented in DNA without the need for additional components, allowing computation to be programmed solely in terms of nucleotide sequences. A major challenge in the design of strand displacement devices has been to enable rapid analysis of high-level designs while also supporting detailed simulations that include known forms of interference. Another challenge has been to design devices capable of sustaining precise reaction kinetics over long periods, without relying on complex experimental equipment to continually replenish depleted species over time. In this paper, we present a programming language for designing DNA strand displacement devices, which supports progressively increasing levels of molecular detail. The language allows device designs to be programmed using a common syntax and then analysed at varying levels of detail, with or without interference, without needing to modify the program. This allows a trade-off to be made between the level of molecular detail and the computational cost of analysis. We use the language to design a buffered architecture for DNA devices, capable of maintaining precise reaction kinetics for a potentially unbounded period. We test the effectiveness of buffered gates to support long-running computation by designing a DNA strand displacement system capable of sustained oscillations.

Compiling DNA Strand Displacement Reactions Using a Functional Programming Language

“…We consider the class of DNA structures introduced in [6]: either single strands or multi-strand gates. For user convenience, we distinguish between upper and lower strands.…”

“…To enable modelling at various levels of detail it is desirable to compile reactions at different levels of abstraction, defined in [6]:…”

“…A key goal is to formalize the structures and interactions of DNA molecules, so that their behaviour may be analyzed [5]. To this end we developed a domain-specific language known as DSD [6], which is a process calculus for describing a particular class of DNA circuits that interact via strand displacement reactions [7]. Prior to the development of the DSD language, strand displacement circuits were largely designed by hand, which was time-consuming and not scalable.…”

Formalizing Modularization and Data Hiding in Synthetic Biology

“…Join gates, on the other hand, are multi-strand DNA constructs that allow for the specification of DNA-based computational processes [14,21,42]. In this approach to DNA computation, one DNA strand that is composed of several logical domains, with all but one domain being hybridized to one or more complementary strands.…”

Plasmid-derived DNA Strand Displacement Gates for Implementing Chemical Reaction Networks

“…DNA strand displacement cascades have been used to create digital and analog molecular circuits [4][5][6][7] , switchable nanostructures [8][9][10] , autonomous molecular motors [11][12][13][14][15] , and non-covalent catalytic amplifiers 13,[16][17][18][19][20][21] . Moreover, DNA devices using strand displacement reactions can be simulated and designed for diverse applications using computer-assisted design software [22][23][24] .…”