Programming cells: Revolutionizing genetic circuits with cutting-edge RNA tools

The research team led by Professor Jongmin Kim from the Department of Life Sciences at POSTECH, along with graduate students Hyunseop Goh and Seungdo Choi, has successfully developed the 'Synthetic Translational Coupling Element (SynTCE),' significantly enhancing the precision and integration density of genetic circuits in synthetic biology. This research was recently published in 'Nucleic Acids Research', an international molecular biology and biochemistry journal.

'Synthetic biology' is a research field that assigns new functions to organisms by leveraging natural and synthetic genetic regulatory tools. Organisms engineered through synthetic biology can be applied in various fields, including disease treatment, plastic-degrading microorganisms, and biofuel production. In particular, the 'polycistronic operon' system, where multiple genes are expressed in coordination to form complexes and perform specific functions, is crucial in maximizing encoding efficiency with limited resources.

However, to precisely design sophisticated genetic circuits, interference between biological parts must be minimized, and encoding density must be increased for efficient gene circuit integration. Synthetic RNA-based translation regulatory parts often encountered limitations in regulating multiple genes and achieving high precision in circuit functionality due to interferences in the protein translation process.

To address this issue, Professor Kim's team focused on 'translational coupling', a natural gene regulation mechanism commonly found in operons that regulate multiple genes, where the translation of upstream genes influences the translation efficiency of downstream genes. Through this research, the team designed 'SynTCE,' which mimics this mechanism, and successfully integrated it with synthetic biological RNA devices to create more efficient genetic circuits.

By integrating SynTCE architecture in an RNA computing system that the team previously reported, the integration density of genetic circuits is greatly enhanced by using SynTCE to accurately transmit input signals to downstream genes, enabling systems with unprecedented capability of simultaneous control for multiple inputs and outputs in a single RNA molecule.

Notably, by precisely controlling protein N-terminals and eliminating interference in protein translation, SynTCE can be applied in 'biological containment^' technology to selectively eliminate targeted cells and direct proteins to programmed cellular locations. This technology is expected to advance precise functional control and facilitate desired biological operations in cells.

Professor Jongmin Kim stated, "This research marks significant progress in enabling sophisticated and accurate genetic circuit design," expressing hope that "this new design will be applied in various fields such as customized cell therapeutics, microorganisms for bioremediation, and biofuel production."

This research was supported by various organizations including the Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry, the National Research Foundation of Korea, Gyeongsangbuk-do and Pohang City's synthetic biology funding, Korea Health Industry Development Institute's Korea Health Technology R&D Project, Gyeongbuk Techno Park support project, Ministry of Education's 4th BK21 support project, Korea Basic Science Institute project, and Leaders In Industry-University Cooperation 3.0 (LINC 3.0).