Journal
SCIENCE
Volume 352, Issue 6281, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac7341
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Funding
- Office of Naval Research, Multidisciplinary University Research Initiative [N00014-13-1-0074]
- Siebel Scholarship
- Air Force Office of Scientific Research
- National Defense Science and Engineering Graduate fellowship [FA9550-11-C-0028]
- National Institute of General Medical Sciences [P50 GMO98792]
- NSF Synthetic Biology Engineering Research Center [SynBERC EEC0540879]
- NSF [1147158]
- NIST Strategic and Emerging Research Initiative
- National Research Council postdoctoral program
- AWS in Education Grant
- Thermo Fischer (Life Technologies) [A114510]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1147158] Funding Source: National Science Foundation
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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 for Escherichia 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.
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