The GRO platform expands the amino acid alphabet to overcome the limitations of protein therapeutics currently impeding the treatment of disease
Our platform comprises Genomically Recoded Organisms (GROs) — the first production organisms with modified genomes and engineered protein translational machinery for high-efficiency production of non-standard amino acid (NSAA) proteins at commercial scale. NSAAs enhance proteins with capabilities inaccessible to the 20 standard amino acids such as unprecedented duration of action and precise control of the immune system.
Click on the hotspots below to see how GROs uniquely enable scalable production of NSAA proteins.
NSAA protein production in a standard organism
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In a standard organism target codons are scattered throughout the genome, leading to off-target incorporation of NSAAs that impairs fitness and productivity. Protein translation machinery also competes with NSAA tRNA for recognition of target codons, driving productivity even lower.
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Target codons are scattered throughout the genome, leading to off-target incorporation of NSAAs and depletion of NSAA tRNA.
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Protein translation machinery such as the Release Factor competes with NSAA tRNA for target codons in the gene of interest, resulting in truncated protein or misincorporation of standard amino acids into the protein product.
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Protein products have low yield and poor activity due to truncation and misincorporation.
NSAA protein production in a Genomically Recoded Organism (GRO)
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In a Genomically Recoded Organism (GRO) all genomic target codons are reassigned to synonymous codons. Only the gene of interest (encoding the therapeutic NSAA protein) contains target codons directing NSAA incorporation. Competitive translational machinery for the target codon is then deleted, resulting in efficient, scalable production of NSAA proteins.
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Target codons are present only in the gene of interest, maintaining high organismal fitness and productivity.
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Protein translation machinery that recognizes the target codon is deleted, removing competition for NSAA incorporation into the protein product.
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Protein products have high yield and novel capabilities empowered by NSAAs.
Biofoundry
Our Biofoundry dramatically accelerates development timelines while standardizing workflows for expanding the NSAA alphabet.
- Adding a new NSAA to the platform requires engineering novel protein translational machinery
- To perform this task we’ve built a Biofoundry that combines state-of-the-art computational protein design tools with high-throughput robotics
- Our Biofoundry workflows bring dramatic acceleration and million-fold increases in sampling, making routine work of the once cumbersome process of engineering NSAA protein translational machinery
- Biofoundry workflows are also heavily utilized to construct and screen libraries of functional NSAA therapeutics produced in the GRO platform
1 – Start with a proprietary database of translational machinery templates
2 – Apply computational protein design tools to templates to generate large libraries of NSAA-specific candidates
3 – Construct designed libraries with automated DNA assembly workflow
4 – Develop customized functional screen specific for the NSAA
5 – Run high-throughput customized screen on the constructed libraries.
6 – Resulting translational machinery has high specificity and activity towards the new NSAA
Additional Chemistries
DuraLogic™
The DuraLogic platform chemistry encompasses a product family integrating non-standard amino acids (NSAAs) to enhance and maintain the three-dimensional structure of proteins needed for therapeutic activity. DuraLogic NSAAs allow creation of proteins with unprecedented duration of action imparting safer and more convenient therapeutic benefits such as flatter pharmacodynamic profiles and relaxed dosing schedules.
A new universe of amino acids
GRObio has access to expansive new therapeutic capabilities provided by non-standard amino acids (NSAAs). Each NSAA is carefully selected to overcome specific limitations found in current therapies.
- GRObio taps into the universe of NSAAs to address pressing unmet clinical needs
- New NSAA chemistries will support a portfolio of protein therapeutics that fulfill the promise of precisely controlled activity, catalysis of novel reactions, defined cellular targeting, and other novel capabilities
- The GRO platform is readily extensible to new NSAAs by leveraging our proprietary Biofoundry
