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Genome engineering

Nature Biotechnology volume 27, pages 1151–1162 (2009)Cite this article

Abstract

For more than 50 years, those engineering genetic material have pursued increasingly challenging targets. During that time, the tools and resources available to the genetic engineer have grown to encompass new extremes of both scale and precision, opening up new opportunities in genome engineering. Today, our capacity to generate larger de novo assemblies of DNA is increasing at a rapid pace (with concomitant decreases in manufacturing cost). We are also witnessing potent demonstrations of the power of merging randomness and selection with engineering approaches targeting large numbers of specific sites within genomes. These developments promise genetic engineering with unprecedented levels of design originality and offer new avenues to expand both our understanding of the biological world and the diversity of applications for societal benefit.

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Figure 1: Milestones in the sizes of de novo synthesized DNA.
Figure 2: Efficiency trends in synthesis and sequencing over the past 30 years (base pairs per dollar).
Figure 3: Examples of engineering at the genome scale.
Figure 4: Current projects in genetic engineering exhibit a trade-off between the scale that can be manipulated and the scale at which one can effectively design.
Figure 5: Chemical synthesis of DNA.
Figure 6: Ligation.
Figure 7: DNA joining by polymerization.
Figure 8: DNA joining by recombination.
Figure 9: DNA assembly in series.
Figure 10: Hierarchical DNA assembly.
Figure 11: DNA assembly in parallel.
Figure 12: Pooling approaches.
Figure 13: Error control.
Figure 14: The general process of assembling large genetic constructs.

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Acknowledgements

The authors wish to acknowledge helpful discussions with J. Jacobson, A. Forster, B. Chow, members of the Church and Jacobson laboratories and the comments of anonymous reviewers. Grant support has been provided by Department of Energy-GTL, National Science Foundation (SynBERC, Center for Bits and Atoms, and Genes and Genomes Systems Cluster) and Defense Advanced Research Projects Agency programmable matter programs.

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  1. Massachusetts Institute of Technology, Media Lab, Center for Bits and Atoms, Massachusetts, Cambridge, USA

    Peter A Carr

  2. Department of Genetics, Harvard Medical School, Massachusetts, Cambridge, USA

    George M Church

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Correspondence to Peter A Carr.

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G.M.C. serves in an advisory role for several companies: Gen9, LS9, Joule Biotechnologies, Sigma-Aldrich. P.A.C. has no competing interests.

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Carr, P., Church, G. Genome engineering. Nat Biotechnol 27, 1151–1162 (2009). https://doi.org/10.1038/nbt.1590

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