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Red blood cells perform many crucial functions, most notably carrying oxygen from the lungs to tissues throughout the body in a loop that repeats thousands of times each day. But what if those same cells were smarter?

A new agreement with the US Defense Advanced Research Projects Agency (DARPA) will bring two labs from the Northwestern University Center for Synthetic Biology (CSB) together with Scarlet Therapeutics Ltd (‘Scarlet’)—a biotech company developing red blood cell-based therapeutics—to advance the development of smart red blood cells (SRBCs).

“This project will develop red blood cells with added functions that help protect a person from physiological insults that occur in extreme environments or after extended exertion,” said Josh Leonard, principal investigator in the Leonard Lab and a professor of chemical and biological engineering. “This project seeks to develop smart red blood cells that can circulate in the body for long periods of time, can sense whether such an insult is occurring, decide how to mitigate the problem, and then act by performing functions such as breaking down toxins and driving the production of substances that fuel muscles and the brain, to help the body cope.”

Leonard’s lab and the lab led by Neha Kamat, associate professor in biomedical engineering, will develop the fundamental synthetic biology ‘parts’ that, when placed in red blood cells, enable them to carry out the “sense, decide, and act” capabilities.

This work builds on over a decade of research experience in engineering novel biological sensors—called receptors—in both living cells and in synthetic systems. Taylor Dolberg (PhD ’20) and Taylor Gunnels (PhD ’24, MS ’22), alumni of the Leonard and Kamat labs, helped the Northwestern team identify how to engineer red blood cells to sense an environmental signal and then turn on an activity in a particular enzyme in response.

Leonard is excited by the potential made possible by this DARPA agreement.

“This DARPA project extends that synthetic biology approach by partnering with Scarlet Therapeutics, a company with expertise in engineering and manufacturing advanced red blood cell-based medicines,” Leonard said. “Together, the team will both pioneer new red blood cell capabilities and evaluate their clinical potential.”

Scarlet Therapeutics is developing a next generation biologics platform that engineers universal red blood cells (RBCs) into long-acting medicines, initially for metabolic disease. The company’s proprietary cell line technology enables scalable manufacturing of lab-grown red blood cells that can carry therapeutic proteins while maintaining the natural safety and circulation properties of RBCs.

Scarlet will lead the project, which also includes collaborators from the University of Bristol in the United Kingdom and Unicorn Biotechnologies.

“We are excited to lead this consortium and to explore how engineered red blood cells can sense and respond to changes in human physiology, while also advancing capabilities in protein retention, biological control, safety and automated manufacturing that could support a new generation of long-acting medicines,” said Bristol professor Ash Toye, chief scientific officer of Scarlet Therapeutics and the principal investigator of the consortium.

For Leonard, the collaboration is another example of the excitement for and possibilities of synthetic biology.

“This project exemplifies the power of synthetic biology—an engineering discipline that enables researchers to break down a complex and ambitious goal into a series of challenging, but realistic steps,” he said. “Ultimately, this ability to engineer living systems in advanced ways unlocks new strategies for addressing unmet societal needs.”

This program is funded by the Defense Advanced Research Projects Agency under Agreement HR0011-26-9-E150. The work is exploratory and intended only to assess feasibility; no clinical use is implied.

About the Center for Synthetic Biology
The Northwestern University Center for Synthetic Biology is home to the first-of-their-kind, U.S. National Science Foundation (NSF)-funded education programs for undergraduate and graduate students to train the next generation of synthetic biologists. Seven startups have emerged from the center in the last several years. And the center’s faculty have played leadership roles within the Engineering Biology Research Consortium, a public-private partnership partially funded by the NSF to advance synthetic biology research to address national and global needs.

Story written by Marc Zarefsky
Feature image created by Ashley Toye using Chat GPT