Irvine, Calif., April 3, 2026 — Many of today’s most serious diseases are driven by harmful proteins inside the body. These proteins can fuel cancer, chronic inflammation and neurodegenerative disorders, yet scientists still do not have good ways to target many of them. In fact, most human proteins are still considered out of reach for traditional drug development. A new study from the lab of Assistant Professor Lauren Albrecht at the UC Irvine Charlie Dunlop School of Biological Sciences offers a promising new way forward. Published in Chem, the research, led by PhD student Laurence Seabrook, introduces a strategy that could help scientists remove disease-causing proteins that were once thought untreatable.
Instead of merely blocking harmful proteins, the researchers focused on helping cells destroy them altogether. Cells already have built-in systems for disposing of unwanted material, but scientists have struggled to redirect those systems toward many of the proteins involved in disease. In this study, the team explored a natural pathway that cells use to break down proteins and then designed small molecules, called MrTACs, that can guide harmful proteins into that pathway for destruction. The approach uses enzymes already found inside cells, making it a potentially powerful platform for future therapies.
Seabrook said the findings are compelling because they could greatly expand what is possible in drug discovery. “Most diseases are driven by proteins, but over 90% of human proteins are considered undruggable because we lack the right tools to target them,” he said. “This research innovates a new solution to address this untouched fraction of human proteins. We discovered an untapped pathway that cells use to degrade proteins, which we could hijack with small molecules called MrTACs (“Mister-TACs”) that send disease-driving proteins to be degraded. This research closes the gaps between fundamental biology and drug discovery by providing a streamlined route to new therapeutics.”
To develop this strategy, the team first studied which proteins cells naturally send through this degradation process. They then identified features that help predict which proteins might be good candidates for MrTAC targeting. From there, they created a flexible, modular design that can be adapted to different protein targets. The study showed that these molecules could selectively degrade multiple disease-linked proteins and improve the effectiveness of existing therapeutic approaches in glioblastoma and cervical cancer models.
Seabrook said designing the molecules required solving a major challenge. “We found that enzymes called protein arginine methyltransferases (PRMTs) can add methyl tags onto proteins, which targets the protein to be degraded in lysosomes,” he said. “By forcing PRMTs into very close proximity with a given protein target, we could initiate this degradation cascade and break down the protein target. We were challenged by the task of designing small molecule MrTACs that could bind both the PRMT and the target at the same time, all while preserving the enzymatic activity of the PRMT. We took lessons from covalent chemistry and allosteric drug design to develop highly effective MrTACs capable of degrading multiple drug targets with high selectivity. We developed a modular, plug-and-play design that can now be easily modified to design MrTACs that bind to new protein targets.”
Looking ahead, the team is exploring how this strategy performs in living disease models and how it might one day help patients. “MrTAC degraders provide a new strategy to stop several diseases, including cancer, chronic inflammation and neurodegeneration,” Seabrook said. “This paper highlights that MrTACs can improve the efficacy and potency of current therapeutics, using glioblastoma and cervical cancer models. We are currently exploring how we can extend the application of MrTAC across in vivo disease models, with the ultimate goal of closing gaps in disease treatment.” With further research and support, this work could help open a new chapter in the fight against diseases driven by hard-to-target proteins.
About the University of California, Irvine Charlie Dunlop School of Biological Sciences:
Recognized for its pioneering research and academic excellence, the Charlie Dunlop School of Biological Sciences plays a crucial role in the university’s status among the nation’s top 10 public universities, as ranked by U.S. News & World Report. It offers a broad spectrum of degree programs in the biological sciences, fostering innovation and preparing students for leadership in research, education, medicine and industry. Nestled in a globally acclaimed and economically vibrant community, the school contributes to the university’s impact as Orange County’s largest employer and a significant economic contributor. Through its commitment to exploring life’s complexities, the Dunlop School embodies the UC Irvine legacy of innovation and societal impact. For more on the Charlie Dunlop School of Biological Sciences, visit https://www.bio.uci.edu/.