Researchers at Arizona State University (ASU) have developed a new method to stabilize engineered genetic programs in cells, addressing a key challenge in synthetic biology. The study, led by Xiaojun Tian, associate professor in the School of Biological and Health Systems Engineering at ASU, was published recently in Cell.
Engineered gene circuits often lose their function as cells grow and divide because important signaling molecules become diluted. To solve this problem, Tian’s team used a principle found in nature called liquid-liquid phase separation. This process allows cells to organize their internal environment by forming small compartments without membranes.
The researchers created microscopic droplets known as transcriptional condensates inside cells. These droplets surround key genes and protect the engineered modifications from being diluted during cell growth.
“When we try to program cells to perform useful tasks, such as diagnostics or therapeutic production, the genetic programs often fail because cell growth dilutes the key molecules needed to keep them running,” Tian said. “We addressed this challenge by tapping into the cell’s own strategy of phase separation to protect engineered systems.”
David Nielsen, a chemical engineering professor in the School for Engineering of Matter, Transport and Energy at ASU, and Wenwei Zheng, an associate professor of chemistry in the School of Applied Sciences and Arts at ASU’s College of Integrative Sciences and Arts, contributed interdisciplinary expertise in synthetic biology, modeling and metabolic engineering.
“We discovered that by forming tiny droplets called transcriptional condensates around genes, we can protect genetic programs and keep them stable even as cells grow,” Zheng said. “It’s a simple physical solution that prevents dilution and keeps circuits running reliably.”
Traditional approaches in synthetic biology have focused on modifying DNA sequences or regulatory feedback loops. Instead, Tian’s team introduced a physical design principle that uses spatial organization within cells.
“Cells already use these droplets to regulate themselves,” Tian said. “We’re now harnessing the same strategy for synthetic biology.”
According to Tian, this approach could help build more reliable biological systems with predictable functions: “This opens a new way to build more reliable living systems, from stable cell factories to future medical applications. Our strategy can become a new design principle for researchers who need their engineered cells to work consistently.”
Microscope images from the study show clusters of transcriptional condensates inside cells that demonstrate where droplets form to stabilize gene activity.
“It’s exciting to see how these droplets can be used to boost bioproduction yields,” Nielsen said. “This kind of collaboration bridges fundamental biological insights with real metabolic engineering applications.”
Tian’s group is now working on engineering different types of condensates to control various genes within cells: “We want to program different condensates to control different genes, creating smart cells that can adapt and function long term,” he said. “We’re learning how to design with the cell, not against it.”
Zheng added: “Researchers in synthetic biology who struggle with unstable circuits will see this as a new way to make their systems more reliable. Bioprocess engineers who want a consistent yield can also use it. For biophysicists like me, it’s exciting to see physical principles like phase separation turned into practical engineering tools.”
“This work reflects a new direction in synthetic biology,” Tian said. “By using the cell’s own organizing principles, we can build systems that are both powerful and inherently stable.”
ASU has been recognized for its innovation efforts; it was named number one in innovation for eight consecutive years by U.S. News & World Report according to this report. The university also ranks highly in undergraduate business, nursing and engineering programs.
Additionally, ASU has partnered with Argos Vision, an ASU tech startup developing smart traffic cameras for Phoenix as part of its broader commitment to innovative solutions.
