Synthorx, a Sanofi Company, La Jolla, California 92037, United States.
J Am Chem Soc. 2021 Apr 7;143(13):4859-4878. doi: 10.1021/jacs.0c11938. Epub 2021 Mar 23.
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 , 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.
几乎所有天然蛋白质都是由 20 种氨基酸组成的，虽然这使得它们能够执行所有功能，但能够编码为特定目的选择的其他氨基酸有望能够发现和生产具有新功能的蛋白质，包括具有更理想的药物特性的治疗性蛋白质。遗传密码扩展 (GCE) 领域多年来一直能够为学术目的生产此类蛋白质，现在正在向商业化生产更优化的蛋白质治疗药物过渡。本文重点介绍，我们回顾了该领域的历史和现状。我们还回顾了第一代商业化努力，总结了经验教训，以及这些经验教训如何指导新的努力。随着学术和工业的不断进步，GCE 方法有望使治疗用途的蛋白质的常规优化成为可能，这在以前只有小分子治疗药物才能实现。
