title: Genetic circuit design automation.
abstract: Computation can be performed in living cells by 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 into 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. We used Cello to design 60 circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 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.
authors.affiliation: Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Alec A K
authors.initials: AA
authors.lastname: Nielsen
authors.affiliation: Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Biological Design Center, Department of Biomedical Engineering, Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA.
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Der
authors.affiliation: Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jonghyeon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Biological Design Center, Department of Biomedical Engineering, Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Vaidyanathan
authors.affiliation: Biosystems and Biomaterials Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20817, USA.
authors.forename: Vanya
authors.initials: V
authors.lastname: Paralanov
authors.affiliation: Biosystems and Biomaterials Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20817, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Strychalski
authors.affiliation: Biosystems and Biomaterials Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20817, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ross
authors.affiliation: Biological Design Center, Department of Biomedical Engineering, Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Densmore
authors.affiliation: Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. cavoigt@gmail.com.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Voigt
mesh_terms: D000465:Algorithms; D020029:Base Pairing; D001483:Base Sequence; D001709:Biotechnology; D004247:DNA / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics*; D053263:Gene Regulatory Networks; D011381:Programming Languages; D012984:Software; D058615:Synthetic Biology
chemical_list: D004247:DNA