Principles of genetic circuit design

Nat Methods. 2014 May;11(5):508-20. doi: 10.1038/nmeth.2926.


Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Clustered Regularly Interspaced Short Palindromic Repeats
  • DNA-Binding Proteins / metabolism
  • Environment
  • Fermentation
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Genetic Engineering / methods*
  • Genetic Vectors
  • Microbiota
  • Prokaryotic Cells
  • Promoter Regions, Genetic
  • RNA Interference
  • Recombinases / metabolism
  • Synthetic Biology / methods*


  • DNA-Binding Proteins
  • Recombinases