ReCODE™ Technology
The Ambrx ReCODE™ technology (reconstituting chemically orthogonal directed engineering) confers unprecedented control over the site-directed placement of chemistry that is designed and demonstrated to be non-disruptive to protein function. Through directed evolution and selection, specialized orthogonal tRNA synthetases (RSo) are evolved to selectively and specifically amino-acylate a similarly orthogonal amber codon-suppressing (M. jannashii) tRNA (tRNAo) with unique, chemically-specified amino acids. The cell's translational apparatus then incorporates the Ambrx amino acid into the elongating peptide sequence at positions designated by the amber codon. In the absence of the Ambrx aa-amino-acyl tRNAo, protein elongation is terminated at amber. Amino acids are designed to include side chains that are chemically-reactive using coupling chemistry that preserves protein function and does not interact with native amino acids. The tRNAo and tRNAo synthetases are orthogonal because they do not interact with endogenous tRNA synthetases and tRNAs, respectively. The proprietary methods for design, evolution, and selection of amino acid and amino-acyl tRNA synthetase pairs have enabled incorporation of over 30 different chemically-specified amino acids into biosynthetic proteins in E. coli, yeast and mammalian cell systems. Ambrx's initial focus has been in the E. coli expression system. Ambrx has evolved the technology through several generations, driving amber suppression to high efficiency and to yields practical for manufacturing.
The components of this reconstituted system are represented in the diagram below, and include the unique amino acid (1), the tRNAo to which it is conjugated by (2) the tRNA synthetase (RSo) to create an amino-acyl tRNA that recognizes (suppresses) (3) the stop codon TAG (amber) (4) placed at any position in the protein of interest's coding sequence. This ReCODE™ technology has been demonstrated to confer engineering proteins for optimal performance, through site-directed placement of chemical reactivity during biosynthesis of the protein.
Ambrx’s proprietary methods for the design, evolution and selection of amino acid and amino-acyl tRNA synthetase pairs have enabled incorporation of over 30 new amino acids into biosynthetic proteins in E. coli, yeast and mammalian cell systems. Ambrx’s initial focus has been on commercialization of its E. coli expression system. Ambrx has evolved the technology to the point of commercial practicality. Importantly, Ambrx has demonstrated that its ReCODE™ technology is efficient, robust and scalable to manufacturing.
At Ambrx, we are committed to developing our own products and to forging collaborations to address the pipeline needs of partners. Our initial product candidates include novel proteins as well as improved versions of marketed, high-value drugs. Importantly, Ambrx’s ReCODE™ technology has broad application across multiple protein classes, including cytokines, peptides, antibodies and across multiple therapeutic areas, including cancer, endocrine disorders, inflammation and infectious disease.
