Expanding and reprogramming the genetic code

Abstract

Nature uses a limited, conservative set of amino acids to synthesize proteins. The ability to genetically encode an expanded set of building blocks with new chemical and physical properties is transforming the study, manipulation and evolution of proteins, and is enabling diverse applications, including approaches to probe, image and control protein function, and to precisely engineer therapeutics. Underpinning this transformation are strategies to engineer and rewire translation. Emerging strategies aim to reprogram the genetic code so that noncanonical biopolymers can be synthesized and evolved, and to test the limits of our ability to engineer the translational machinery and systematically recode genomes.

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Figure 1: The natural translational machinery performs encoded amino acid polymerization.
Figure 2: Genetic code expansion for ncAA incorporation into proteins in vivo and its use for creating attenuated viruses.
Figure 3: Strategies to go beyond nonsense codons for the incorporation of multiple distinct unnatural monomers.

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Acknowledgements

I thank A. Chatterjee, K. Wang, and P. G. Schultz for suggestions and edits to earlier versions of the manuscript and V. Beranek, and K. Wang for assistance with figures. Work in my laboratory is supported by the Medical Research Council, UK (MC_U105181009 and MC_UP_A024_1008) and an ERC Advanced Grant (SGCR).

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Correspondence to Jason W. Chin.

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Reviewer Information Nature thanks A. C. Forster, A. Schepartz and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Chin, J. Expanding and reprogramming the genetic code. Nature 550, 53–60 (2017). https://doi.org/10.1038/nature24031

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