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Winter 2024

Targeting shapeshifting proteins for drug development

By: Kristy Wendt

New Madison-based biotech platform company Immuto Scientific demystifies protein structure for dynamic “undruggable” proteins.

Proteins constantly shapeshift in living beings, wiggling and transforming their three-dimensional shape to adapt to the body’s ever-changing flow of chemical and environmental cues. This flexibility is essential for the day-to-day functions of proteins that recognize and bind other molecules, turn bodily functions on and off, and transmit messages within and between cells. 

However, the many shapes a protein can assume can also be the bane of medical researchers attempting to stop diseased proteins.

Recent work has developed new methods to capture these moving targets. Through their doctoral work in the electrical engineering laboratory of Professor Leon Shohet, fellow alums Dr. Faraz Choudhury and Dr. Dan Benjamin collaborated with biochemistry professor Dr. Michael Sussman to invent a new technology aimed at identifying these “undruggable” proteins in living cells.

The technology, called Plasma Induced Modification to Biomolecules (PLIMB), is patented by the Wisconsin Alumni Research Foundation (WARF) and is a foundation of Immuto Scientific, the company that Choudhury and Benjamin co-founded in 2018.

“The seed for every drug discovery program is starting with sometimes difficult-to-characterize proteins in the human body,” Choudhury says. “Designing a drug is kind of like designing a key for a lock. You must have a better understanding of what the lock looks like to design a key that fits.”

Potential applications for PLIMB include Chimeric Antigen Receptor (CAR) T-cell therapy, a breakthrough form of cancer care that modifies a patient’s white blood cells, enabling them to better recognize and attack cancer cells.

“[PLIMB] allows us to identify specific structures unique to tumors to help clients design therapies that only bind to the tumor cells and not go after healthy tissues,” Choudhury explains. “One of the biggest issues with CAR-T right now is that the targets are not highly tumor specific and have a lot of side effects that fail in the clinic. We work with immuno-oncology programs as well as just standard antibodies for different diseases [through our] unique capabilities in [identifying] disease-related protein structures.”

While the traditional method for characterizing protein structure can take several months per sample and entails removing the protein from its native environment, Immuto strives to overcome these difficulties.

“A unique aspect of the technology is that we can identify protein structures directly in living cells in the most native conformation and environment of the protein,” Choudhury says. Further, Immuto internally runs about 100 samples a day, including analyses.

 “Our speed is unprecedented,” Choudhury notes. “Patient samples contain hundreds of thousands of protein structures, and we can analyze these samples with a throughput that matches the scale. We’re the only platform in the industry that enables that sort of analysis.” 

Choudhury receives funds from multiple Madison-based accelerator programs for graduate students and postdocs to support his company, including WARF, Discovery to Product (D2P), Gener8tor, gBETA, and Merlin Mentors. He encourages other burgeoning inventors on campus to do the same.

“Designing a drug is kind of like designing a key for a lock. You must have a better understanding of what the lock looks like to design a key that fits.”

– Dr. Faraz Choudhury

“Even before we raised our first round of funding, we tapped into resources in Madison and the University of Wisconsin-Madison community. There are challenges, but I would say there are many resources if someone’s really interested,” Choudhury explains.

Immuto Scientific is currently focused on expansion and commercialization, working to form partnerships with medical researchers and pharmaceutical companies. Together, they aim to develop more precise, targeted therapies with fewer side effects for patients.

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