A research team led by Professor Jongmin Kim of the Department of Life Sciences at POSTECH, along with graduate students Taeyang Heo, Dongwon Park, and Woosub Shin, has developed the 'SUPER (Synthetic Upcycling Platform for Engineering Regulators)' platform, which dramatically enhances the performance and stability of gene regulatory devices. This research was recently published in Advanced Science , an international peer-reviewed journal.
Synthetic biology utilizes genetic components as programmable building blocks to endow cells with new functions. As such, synthetic biology is poised to revolutionize bioengineering and biotechnology in addressing future challenges. The adoption of synthetic genetic switches that control genes 'ON' and 'OFF' is accelerating due to the advantages of compact and modular architecture and strong performance for developing next-generation biosensors, cell-based therapeutics, and biofactories.
Still, a critical challenge remains for these synthetic genetic switches where the ‘OFF’ state is not really OFF at the molecular level. Much like a dripping faucet even when completely turned off, genetic switches continue to express at low levels even in the 'OFF' state—a phenomenon known as 'leakage.' Although it may look harmless on the surface, this small leakage can accumulate over time, place a long-term metabolic burden on cells, and compromise circuit stability, ultimately requiring a complete overhaul of the system.
To address this challenge, the team developed ‘SUPER’, a platform technology that utilizes synthetic small RNAs as add-on controllers for genetic switches. This principle is analogous to inserting an extra gasket into a leaky faucet to restore its function. The key advantage of ‘SUPER’ is to bypass engineering target devices altogether, yet still achieve dramatically enhanced functionality by simple add-on controllers.
When enhanced with the SUPER platform, natural and synthetic genetic switches showed performance improvements of up to 1,011% with a tunable dynamic range—the ability to distinguish between ON and OFF signals—up to 22,000-fold. These performance metrics could be easily adjusted by small RNAs in the SUPER platform, thereby enabling flexible, context-dependent regulation of synthetic genetic switches.
Building on this foundational technology, the team also demonstrated dramatic improvement in cellular 'kill switches'—safety mechanisms designed to prevent unintended spread of engineered organisms in gene therapy and bioprocessing. Previously, kill switch circuits often suffered from residual leaky expression that could lead to loss of functional circuits and the emergence of resistance in cells. Kill switches enhanced with SUPER remained stable for over 30 days in engineered cells, with the ability to integrate environmental signals such as chemical inputs and temperature.
Professor Jongmin Kim stated, "SUPER is an upcycling technology that enhances both the performance and stability of existing genetic components without changing those components." He added, "With SUPER, we anticipate that a wide array of genetic parts that were previously overlooked could be put to use for broad application areas including live biotherapeutics and biomanufacturing“.
This research was supported by the Korea Health Industry Development Institute, the Gyeongsangbuk-do and Pohang City Synthetic Biology Support Program, the Ministry of Education BK21 FOUR Program, Gyeongbuk Technopark, the Ministry of Agriculture, Food and Rural Affairs' Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry, the Korea Basic Science Institute, and the National Research Foundation of Korea.
Advanced Science
SUPER: Upcycling Genetic Parts for Precise Gene Expression Control, Leakage Minimization, and Genetic Circuit Stability
15-Dec-2025