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Genetic circuit design automation

Published

Author(s)

Alec Nielsen, Bryan Der, Jonghyeon Shin, Prashant Vaidyanathan, Douglas Densmore, Vanya M. Paralanov, Elizabeth A. Strychalski, David J. Ross, Christopher Voigt

Abstract

Computation can be performed in living cells using DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part assembly and balancing of regulator expression. We describe a design environment (Cello), in which a user writes Verilog code that is automatically transformed to a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. Using Cello, 60 circuits were designed for E. coli (0.88 Mbp of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly (up to 10 regulators and 55 parts), and across the full set 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization.
Citation
Science
Volume
352
Issue
6281

Keywords

Synthetic biology, systems biology, genetic compiler, DNA synthesis, abstraction, standards, programming language, logic synthesis
Created April 1, 2016, Updated November 10, 2018