AminoX: Making Better Protein Drugs, Quicker and Cheaper

The Problem

Protein drugs often offer the most effective way to treat a variety of medical illnesses and conditions. However, many proteins in their naturally occurring forms make poor drugs – they can cause toxicities that force patients to discontinue treatment, and they often have such short half-lives that patients would need to receive a constant infusion of them to see a therapeutic effect.

Recently, blockbuster drugs Saxenda^Ⓡ and Ozempic^Ⓡ/Wegovy^Ⓡ have overcome this problem by adding non-standard amino acids (nsAAs) to the hormone GLP-1, dramatically extending its persistence in the body. While using nsAAs to give proteins new abilities has the potential to unlock a plethora of new drugs, synthesizing proteins with nsAAs is an extremely inefficient and time-consuming process. It can take up to a full year to synthesize a protein that contains a single nsAA, limiting the ability of the pharma industry to bring improved protein drugs to market.

Our Solution

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The Wyss Institute’s AminoX platform technology has overcome this bottleneck by inventing and patenting a novel chemistry that has revolutionized the 50-year-old process of synthesizing proteins in the lab. This new approach enables the incorporation of almost any off-the-shelf nsAA into proteins with a simple process that can be done at the bench with 10 times the efficiency of existing methods. It reduces the work of days to a process that can be completed within hours, enabling the rapid testing and iteration of novel protein drugs.

To incorporate nsAAs into protein drugs, AminoX uses a synthetic biology approach that hacks the biological process cells use to synthesize their proteins. This method enables the generation of functional intermediates that can effectively hand over their nsAAs directly to the ribosome in a scalable and specialized cell-free process. Crucially, a single intermediate can incorporate nearly any nsAA, whereas other existing methods require the creation of a new intermediate for every single nsAA. AminoX also incorporates machine learning approaches to identify new nsAA designs with therapeutic potential and candidate positions in protein sequences at which to insert nsAAs, enabling the rapid testing of multiple variants of a protein drug containing nsAAs at different positions.

Product Journey

The AminoX team formed at the Wyss Institute when Erkin Kuru from George Church’s group, Helena de Puig from James Collins’ group, started to discuss the potential of nsAAs, which they have been already exploring for diagnostic applications, as means to create better therapeutics. Erkin Kuru is an expert in the development of nsAAs and the chemistry of in vitro protein synthesis, and Helena de Puig had previously developed smart materials with diagnostic capabilities using CRISPR technology. Erkin Kuru and Helena de Puig were joined by Michaël Moret, another member of Church’s group who complements the team with critical computational, machine learning, and drug discovery expertise. Other scientific team members are Allison Flores and Subhrajit Rout. On AminoX’s validation path and its first focus on irAEs and nsAA-enhanced immune checkpoint inhibitor drugs, the team is advised by Girija Goyal, a member of Donald Ingber’s group, on questions involving the human immune system, and Wyss technology development experts Sylvie Bernier and Ken Carlson, as well as business development expert Bill Bedell.

Impact

The AminoX team formed at the Wyss Institute when Erkin Kuru from George Church’s group and Helena de Puig from James Collins’ group started to discuss the potential of nsAAs, which they had been already exploring for diagnostic applications, as means to create better therapeutics. Kuru is an expert in the development of nsAAs and the chemistry of in vitro protein synthesis, and de Puig had previously developed smart materials with diagnostic capabilities using CRISPR technology. The two were subsequently joined by Michaël Moret, another member of Church’s group who complements the team with critical computational, machine learning, and drug discovery expertise.

The AminoX team was able to apply their platform to >42 new nsAAs within one year in an academic setting. They demonstrated the utility of their platform by creating fluorescent biosensors that fluoresced immediately upon detection of their target, eliminating most of the cumbersome wash steps used in standard ELISA detection assays.

Based on its potential to rapidly create superior protein drugs in multiple therapeutic areas, AminoX was selected as a high-priority 2023 Wyss Institute Validation Project. In 2024, it was named a Northpond Project in collaboration with Northpond Labs, and received additional support to widen the set of novel chemistries with which they can endow proteins, including antibodies and oncoproteins.