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Synthetic evolution

Abstract

The combination of modern biotechnologies such as DNA synthesis, λ red recombineering, CRISPR-based editing and next-generation high-throughput sequencing increasingly enables precise manipulation of genes and genomes. Beyond rational design, these technologies also enable the targeted, and potentially continuous, introduction of multiple mutations. While this might seem to be merely a return to natural selection, the ability to target evolution greatly reduces fitness burdens and focuses mutation and selection on those genes and traits that best contribute to a desired phenotype, ultimately throwing evolution into fast forward.

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Fig. 1: Directed mutagenesis of targeted genes.
Fig. 2: Compartmentalization-mediated evolution.
Fig. 3: Shuffling-based hybridization of genes and genomes.
Fig. 4: Recombineering-based continuous evolution.
Fig. 5: CRISPR tools for genome evolution.
Fig. 6: Continuous evolution by host-mediated mutagenesis.
Fig. 7: Continuous self-evolution.

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Acknowledgements

This work was funded by the Air Force Office of Scientific Research (FA9550-14-1-0089) and by an Arnold O. Beckman Postdoctoral Fellowship held by A.J.S.

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Correspondence to Andrew D. Ellington.

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A.D.E is cofounder and advisor at GRO Biosciences, Inc, which is using computational protein design and synthetic biology to develop protein therapeutics. A.D.E has filed intellectual property disclosures that reference Compartmentalized Partner Replication: 6761ELL ‘Thermostable reverse transcriptase based on a thermostable DNA polymerase,’ US 15/410, 211, Japan 2018-538718 and EP 17741900.9, filed on 1/19/17; and 7151 ELL ‘A method for screening metabolites and their receptors’ PCT/US2018/037818, filed on 6/15/18.

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Simon, A.J., d’Oelsnitz, S. & Ellington, A.D. Synthetic evolution. Nat Biotechnol 37, 730–743 (2019). https://doi.org/10.1038/s41587-019-0157-4

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