Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Realizing the potential of synthetic biology

Nature Reviews Molecular Cell Biology volume 15, pages 289–294 (2014)Cite this article

Subjects

Abstract

Synthetic biology, despite still being in its infancy, is increasingly providing valuable information for applications in the clinic, the biotechnology industry and in basic molecular research. Both its unique potential and the challenges it presents have brought together the expertise of an eclectic group of scientists, from cell biologists to engineers. In this Viewpoint article, five experts discuss their views on the future of synthetic biology, on its main achievements in basic and applied science, and on the bioethical issues that are associated with the design of new biological systems.

An increasing number of publications and institutions are dedicated to synthetic biology. From the initial focus on the design of synthetic genetic circuits, how has the field expanded and evolved? And how does synthetic biology today relate to other disciplines such as systems biology and mathematical modelling?

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Hasty, J., McMillen, D. & Collins, J. J. Engineered gene circuits. Nature 420, 224–230 (2002).

    Article  CAS  Google Scholar 

  2. Wang, Y. H., Wei, K. Y. & Smolke, C. D. Synthetic biology: advancing the design of diverse genetic systems. Annu. Rev. Chem. Biomol. Eng. 4, 69–102 (2013).

    Article  Google Scholar 

  3. Dymond, J. S. et al. Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature 477, 471–476 (2011).

    Article  CAS  Google Scholar 

  4. Khalil, A. S. & Collins, J. J. Synthetic biology: applications come of age. Nature Rev. Genet. 11, 367–379 (2010).

    Article  CAS  Google Scholar 

  5. Voigt, C. A. Synthetic biology. ACS Synth. Biol. 1, 1–2 (2012).

    Article  CAS  Google Scholar 

  6. Endy, D. Foundations for engineering biology. Nature 438, 449–453 (2005).

    Article  CAS  Google Scholar 

  7. Smolke, C. D. & Silver, P. A. Informing biological design by integration of systems and synthetic biology. Cell 144, 855–859 (2011).

    Article  CAS  Google Scholar 

  8. Wang, H. H. et al. Programming cells by multiplex genome engineering and accelerated evolution. Nature 460, 894–898 (2009).

    Article  CAS  Google Scholar 

  9. Church, G. M. & Regis E. Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves (Basic Books, 2012).

    Google Scholar 

  10. Win, M. N. & Smolke, C. D. Higher-order cellular information processing with synthetic RNA devices. Science 322, 456–460 (2008).

    Article  CAS  Google Scholar 

  11. Bonnet, J., Yin, P., Ortiz, M. E., Subsoontorn, P. & Endy, D. Amplifying genetic logic gates. Science 340, 599–603 (2013).

    Article  CAS  Google Scholar 

  12. Mutalik, V. K. et al. Precise and reliable gene expression via standard transcription and translation initiation elements. Nature Methods 10, 354–360 (2013).

    Article  CAS  Google Scholar 

  13. Kelly, J. R. et al. Measuring the activity of BioBrick promoters using an in vivo reference. J. Biol. Eng. 3, 4 (2009).

    Article  Google Scholar 

  14. Liang, J. C., Chang, A. L., Kennedy, A. B. & Smolke, C. D. A high-throughput, quantitative cell-based screen for efficient tailoring of RNA device activity. Nucleic Acids Res. 40, e154 (2012).

    Article  CAS  Google Scholar 

  15. Michener, J. K. & Smolke, C. D. High-throughput enzyme evolution in Saccharomyces cerevisiae using a synthetic RNA switch. Metab. Eng. 14, 306–316 (2012).

    Article  CAS  Google Scholar 

  16. Czar, M. J., Anderson, J. C., Bader, J. S. & Peccoud, J. Gene synthesis demystified. Trends Biotechnol. 27, 63–72 (2009).

    Article  CAS  Google Scholar 

  17. Carr, P. A., Sun, Z. Z., Xu, G., Forest, C. R. & Church, G. M. Programming cells by multiplex genome engineering and accelerated evolution. Nature 460, 894–898 (2009).

    Article  Google Scholar 

  18. Gibson, D. G. et al. Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. 339, 819–823 (2008).

  19. Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. 319, 1215–1220 (2013).

  20. Xia, B., Leguia, M., Anderson, J. C. & Densmore, D. Eugene — a domain specific language for specifying and constraining synthetic biological parts, devices, and systems. PloS ONE 6, e18882 (2011).

    Article  Google Scholar 

  21. Czar, M. J., Cai, Y. & Peccoud, J. Writing DNA with GenoCAD™. Nucleic Acids Res. 37, W40–W47 (2009).

    Article  CAS  Google Scholar 

  22. Hillson, N. J., Rosengarten, R.D. & Keasling, J.D. j5 DNA assembly design automation software. ACS Synth. Biol. 1, 14–21 (2011).

    Article  Google Scholar 

  23. Tran, A. B., Paull, M., Keasling, J. D., Arkin, A. P. & Endy, D. Precise and reliable gene expression via standard transcription and translation initiation elements. Nature Methods 10, 354–360 (2013).

    Article  Google Scholar 

  24. Brophy, J. A. N., Clancy, K., Peterson, T. & Voigt, C. A. Characterization of 582 natural and synthetic terminators and quantification of their design constraints. Nature Methods 10, 659–664 (2013).

    Article  Google Scholar 

  25. Rhodius, V. A. et al. Design of orthogonal genetic switches based on a crosstalk map of σs, anti-σs, and promoters. Mol. Syst. Biol. 9, 1–13 (2013).

    Google Scholar 

  26. Stanton, B. C. et al. Genomic mining of prokaryotic repressors for orthogonal logic gates. Nature Chem. Biol. 10, 99–105 (2014).

    Article  CAS  Google Scholar 

  27. Schirmer, A., Rude, M. A., Li, X., Popova, E. & del Cardayre, S. B. Microbial biosynthesis of alkanes. Science 329, 559–562 (2010).

    Article  CAS  Google Scholar 

  28. Mali, P., Esvelt, K. M. & Church, G. M. Cas9 as a versatile tool for engineering biology. Nature Methods 10, 957–963 (2013).

    Article  CAS  Google Scholar 

  29. Ruder, W. C., Lu, T. & Collins, J. J. Synthetic biology moving into the clinic. Science 333, 1248–1252 (2011).

    Article  CAS  Google Scholar 

  30. de Jager, V. et al. antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res. 39, W339–346 (2011).

    Article  Google Scholar 

  31. Tumpey, T. M. et al. Characterization of the reconstructed 1918 spanish influenza pandemic virus. Science 310, 77–80 (2005).

    Article  CAS  Google Scholar 

  32. Lajoie, M. J. et al. Genomically recoded organisms impart new biological functions. Science 342, 357–360 (2013).

    Article  CAS  Google Scholar 

  33. Lajoie, M. J. et al. Probing the limits of genetic recoding in essential genes. Science 342, 361–363 (2013).

    Article  CAS  Google Scholar 

  34. Elowitz, M. & Lim, W. A. Build life to understand it. Nature 468, 889–890 (2010).

    Article  CAS  Google Scholar 

  35. Danino, T. et al. A synchronized quorum of genetic clocks. Nature 463, 326–330 (2010).

    Article  CAS  Google Scholar 

  36. Stricker, J. et al. A fast, robust and tunable synthetic gene oscillator. Nature 456, 516–519 (2008).

    Article  CAS  Google Scholar 

  37. Fung, E. et al. A synthetic gene-metabolic oscillator. Nature 435, 118–122 (2005).

    Article  CAS  Google Scholar 

  38. Elowitz, M. B. & Leibler, S. A. Synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2010).

    Article  Google Scholar 

  39. Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).

    Article  CAS  Google Scholar 

  40. Nandagopal, N. & Elowitz M. B. Synthetic Biology: integrated gene circuits. Science 333, 1244–1248 (2011).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

G.M.C. is supported by grants from the US Department of Energy (DOE), US Defense Advanced Research Projects Agency (DARPA), US National Human Genome Research Institute (NHGRI), US National Science Foundation (NSF) and Personal Genome Project (PGP). C.D.S. is supported by funds from the US National Institutes of Health (NIH), NSF, DARPA, Human Frontiers Science Program (HFSP), and Bill and Melinda Gates Foundation.

Author information

Authors and Affiliations

  1. The Department of Genetics, Harvard Medical School, Harvard University, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.,

    George M. Church

  2. The Division of Biology and Biological Engineering and Department of Applied Physics, Howard Hughes Medical Institute, California Institute of Technology (Caltech), M/C 114-96, Pasadena, California 91125, USA.,

    Michael B. Elowitz

  3. The Stanford University School of Medicine, 473 Via Ortega, University of Stanford, Stanford, California 94305, USA.,

    Christina D. Smolke

  4. Department of Biological Engineering, The Synthetic Biology Center, Massachusetts Institute of Technology (MIT), 500 Technology Square, Cambridge, Massachusetts 02139, USA.,

    Christopher A. Voigt

  5. Department of Biological Engineering, Department of Electrical Engineering and Computer Science, The Synthetic Biology Center, Massachusetts Institute of Technology (MIT), NE47-223, 500 Technology Square, Cambridge, Massachusetts 02139, USA.,

    Ron Weiss

Authors
  1. George M. Church
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael B. Elowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christina D. Smolke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher A. Voigt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ron Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Michael B. Elowitz, Christina D. Smolke, Christopher A. Voigt or Ron Weiss.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

George M. Church's homepage

Michael B. Elowitz's homepage

Christina D. Smolke's homepage

Glossary

CRISPR

(Clustered regularly interspaced short palindromic repeats). An adaptive immune system that is found in bacteria and archaea, which is based on an RNA-guided nuclease (Cas9). Components of the CRISPR system are being repurposed to provide powerful, flexible and precise genome engineering, and regulatory systems across diverse species.

Genetic switches

Natural or synthetic systems for regulating gene expression in response to one or more external or internal signals. The output of genetic switches is often a complex logical function of input signals that in many cases can provide a persistent response to transient inputs or other capabilities.

Genomically recoded organisms

(GROs). Changing every instance in a genome of one or more of the 64 codons in the genetic code for higher safety and productivity.

Multiplex-automated genome engineering

(MAGE). Efficient genome editing that is capable of making dozens of changes per genome and billions of genomes by inserting short (90 bases long) single-stranded DNA into the cellular replication fork with one or more DNA changes.

Optogenetics

A technique to control and perturb cellular behaviour using light and genetically encoded light-sensitive proteins. It has been extensively used to precisely control neuronal activity spatially and temporally through light.

Oscillator

Produces oscillations that underlie diverse biological behaviours from neurobiology to multicellular development. Synthetic biology has shown that remarkably simple circuit designs can produce clock-like oscillations of protein levels in individual living cells.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Church, G., Elowitz, M., Smolke, C. et al. Realizing the potential of synthetic biology. Nat Rev Mol Cell Biol 15, 289–294 (2014). https://doi.org/10.1038/nrm3767

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm3767

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research