Abstract
Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits.
Highlights
Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments
In addition to software tools that facilitate automated design and analysis of DNA strand displacement circuits, we need to simplify the experimental procedures for creating these circuits in vitro, so that it is possible for researchers with diverse backgrounds to build their own circuits and explore potential applications
We show that one can successfully build a complex DNA strand displacement circuit, using DNA sequences automatically generated from a molecular compiler
Summary
Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. We demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. In addition to software tools that facilitate automated design and analysis of DNA strand displacement circuits, we need to simplify the experimental procedures for creating these circuits in vitro, so that it is possible for researchers with diverse backgrounds to build their own circuits and explore potential applications. We show that one can even do so using cheap, unpurified DNA strands, following simple and systematic experimental procedures
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