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Coming together to engineer new treatments for serious diseases

Three researchers from different disciplines and faculty labs joined forces to develop AminoX, a technology that uses non-standard amino acids to improve protein therapies

Coming together to engineer new treatments for serious diseases
This photo shows AminoX team members Michaël Moret, Helena de Puig, and Erkin Kuru (from left to right) at the Wyss Institute. Credit: Wyss Institute at Harvard University

By Jessica Leff

Immunotherapy is often seen as the next frontier in cancer treatment, offering many benefits over traditional therapies like radiation and chemotherapy. Unfortunately, immunotherapy patients frequently experience painful side effects because antibodies affect healthy tissues along with the tumor. What if these drugs could more accurately target cancer cells, improving existing therapeutics and opening new options for cancer patients and beyond?

Assembling the team

Chemist Erkin Kuru began working in the lab of Core Faculty member George Church in 2016. He focused on using non-standard amino acids to augment proteins, first concentrating on enhancing them with a fluorescent property. A year later, mechanical engineer Helena de Puig joined the lab of Core Faculty member Jim Collins. In 2020, the two began collaborating with the idea that they could take advantage of de Puig’s experience in disease diagnostics and high-throughput antibody screening to develop a new class of instant diagnostics using Kuru’s fluorescent amino acids. Soon, they realized they could pivot from diagnosing diseases to treating them by using non-standard amino acids to endow proteins with new-to-nature functions. Thus, AminoX was born.

Once you have a technology in your hands that can be used to generate therapies for serious diseases like cancer, you’re making a mistake if you’re not trying to do that.

Helena de Puig

In August of 2022, Michaël Moret joined the Church lab and quickly became part of the team, sharing his expertise in machine learning and drug discovery. The three continued to refine their work, and AminoX became a Wyss Validation Project in July 2023.

Now, the three work together seamlessly, speaking to each other daily to continue to develop their ideas and plan the future of the project. De Puig’s familiarity with product development through her previous experiences makes her the natural leader. Moret handles the computational aspects, along with research and literature review on the drug discovery side. Kuru has been working with non-standard amino acids for more than a decade, so he focuses on the chemistry. Kuru explains, “Our complimentary expertise makes this AminoX project really shine.”

Cancer and beyond

The team has ambitions beyond helping cancer immunotherapies better target tumors. They eventually aim to address several problems that cannot be solved with the 20 naturally occurring amino acids. This could range from treating autoimmune diseases to resurrecting existing protein therapies that failed in clinical trials because they were cleared too quickly from the body or couldn’t bind to their target strongly enough.

Medicinal chemists have been working for decades to take a small molecule and perfect it for therapeutic effects. Now, we’re able to do the same thing to proteins, incorporating non-standard amino acids.

Erkin Kuru

De Puig explains, “While others are evolving cellular machinery to incorporate one new non-standard amino acid [into a protein], we’ve discovered chemistry that allows us to actually incorporate an unprecedend amount of non-standard amino acid without the need to evolve the cellular machinery at all.”

A uniquely Wyss project

This project perfectly exemplifies the multidisciplinary, collaborative nature of the Wyss Institute, where working with researchers from different faculty labs is encouraged.

Since AminoX became a Validation Project, the team has further benefitted from everything the Institute has to offer. They are connecting and collaborating with researchers across various disciplines, accelerating the de-risking of their technology.

Research Fellow Subhrajit Rout, who specializes in organic chemistry, and graduate student Allison Flores round out the team. They’re incredibly grateful for the support from multiple members of the Advanced Technology Team: Sylvie Bernier, Ken Carlson, Jim Niemi, Girija Goyal, and Jenny Tam, along with Business Development Manager, Bill Bedell, and Associate Director of IP, Vani Velamoor. Though none of them are members of his lab, Founding Director Donald Ingber also advises the team.

Forward thinking has been so helpful to this project and is an essential part of the Wyss. If in 20 years small molecules are still one of the main ways we treat people, it would be very sad because of how limited they are. We’re considering, how can we solve these problems now in a more intelligent way?

Michaël Moret

As the team further refines and de-risks their technology with the goal of eventually forming a startup, they’re looking for investors, as well as industry partners focused on biologics for partnerships. If you are interested in helping to accelerate the development of AminoX, please get in touch with Bill Bedell.

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