Bioengineering Programmable Cytokines: Redesigning Immune Communication for Safer, Smarter Immunotherapies
“Just as language enabled humans to build civilizations, protein-based communication has enabled single cells to evolve into complex organisms,” says Dr. Mohamad Abedi, recipient of the 2026 Michelson Prizes: Next Generation Grants. In particular, cytokines are the master orchestrators of immune responses, telling other immune cells what to do and where to do it, in order to protect the body. Yet despite their central role, we have yet to harness their power for therapeutics. Once unleashed, we are unable to control their actions, resulting in severe side effects and toxicity. Abedi aims to tame this force by designing smarter, targeted synthetic cytokines engineered with sensors that control exactly where and when they are activated. “Instead of taking a natural protein and trying to engineer around its flaws, we can design the right molecule for the job,” he says.
Abedi’s ambitious goals are inspired by his training under Nobel Laureate David Baker at the Institute for Protein Design, where he used AI-driven tools to generate novel cytokines not found in nature, laying the groundwork for his aspirations to engineer programmable immunotherapies. “By learning to precisely decode and engineer signaling systems, we can design more effective and predictable therapies that directly reprogram cellular behavior,” he says. “At its core, this work is about understanding the language of cells and learning how to speak it.”
Born a refugee and later immigrating to the United States at age 17, Abedi is no stranger to speaking different languages. He learned how to speak Arabic, French, and English as a child. Now having learned the language of immunology, Abedi will design what he calls “inducikines,” which are cytokines activated only in specific locations, such as within tumors. Prior attempts at cytokine immunotherapies have lacked these controls, which is why they have largely failed due to toxicity. “What we need is a sensor system that allows the cytokine to circulate throughout the body but only activate when it senses it is in a tumor. Recent advances in computational protein design now make this possible. We can design the perfect protein from scratch on a computer. We start with the desired function, then generate the structure computationally. This bypasses millions of years of evolution to build molecules with exactly the properties we need,” he says.
The grant will provide Abedi with the resources to design cytokines that sense molecules found only in tumor tissue and trigger their activation to drive an immune attack on tumor cells. But Abedi won’t stop there. “While environmental cues can help define where disease occurs, therapeutic precision also requires deciding which cells should respond to a cytokine,” he says. Abedi will prevent side effects and toxicity caused by off-target effects on unwanted cell types by adding a blocking sensor. When the sensor detects unique molecular fingerprints found on these cells, it will turn off the cytokine. The innovative strategy will enable Abedi to fine-tune his programmable cytokines to achieve the safety and efficacy that natural cytokines cannot. Ultimately, his vision is to combine these approaches and design molecules that integrate multiple signals, like a molecular logic gate, activating only when the right combination code is present.
The project is a perfect fit for the Michelson Prizes: Next Generation Grants, probing the foundational principles of immunology with the potential to transform medicine. “If we succeed, the payoff could be enormous. We would gain an entirely new therapeutic modality that has been largely inaccessible until now,” says Abedi. These cytokine-based therapies could have far reaching impacts beyond cancer. Because cytokines regulate inflammation, tissue repair, and other essential immune functions, engineered cytokines could be used to treat autoimmune diseases, chronic inflammatory disorders, infectious diseases, and promote tissue regeneration. These same protein design principles can be extended to other signaling molecules, such as growth factors or hormones, to open up more therapeutic possibilities. “Cytokines are just the starting point. Over time, this could enable entirely new classes of biologic drugs with built-in precision, safety, and programmable behavior beyond what nature evolved.”
Abedi’s work lives at the intersection of bioengineering, synthetic biology, immunology and clinical research. These disparate fields are essential to innovation, bringing fresh perspectives required to achieve true breakthroughs. “I started working on cytokines during my postdoc, with no prior experience. This lack of preconceptions was actually an advantage. I did things that others might have considered crazy,” says Abedi. Indeed, Abedi personifies the Michelson Medical Research Foundation philosophy that diverse expertise, disruptive concepts, and unconventional approaches are necessary to tackle today’s greatest immunology challenges and redefine the future of immunotherapy. “If we succeed in truly understanding the language of cells, the therapeutic opportunities that emerge may be ones we didn't even know existed,” says Abedi.
