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Genetic Code Expansion: Inception, Development, Commercialization

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 143, Issue 13, Pages 4859-4878

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c11938

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Almost all natural proteins consist of only 20 amino acids, but the ability to encode other amino acids opens up the possibility of producing proteins with novel functions, including more optimal therapeutic proteins. The field of genetic code expansion is moving towards commercialization for the production of improved protein therapeutics through academic and industrial progress.
Virtually all natural proteins are built from only 20 amino acids, and while this makes possible all the functions they perform, the ability to encode other amino acids selected for specific purposes promises to enable the discovery and production of proteins with novel functions, including therapeutic proteins with more optimal drug-like properties. The field of genetic code expansion (GCE) has for years enabled the production of such proteins for academic purposes and is now transitioning to commercialization for the production of more optimal protein therapeutics. Focusing on E. coli, we review the history and current state of the field. We also provide a review of the first generation commercialization efforts, the lessons learned, and how those lessons are guiding new efforts. With continued academic and industrial progress, GCE methodologies promise to make possible the routine optimization of proteins for therapeutic use in a way that has only previously been possible with small-molecule therapeutics.

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