Circular mRNA helps cell factories make up to six times as much protein
A synthetic biology technology has been developed that converts easily degraded messenger RNA (mRNA) into a ring-shaped form inside microbial cells, increasing protein production.
Researchers from Seoul National University College of Engineering have created a new synthetic biology technology that converts linear messenger RNA (mRNA) into a circular form within microbial cells. This innovation, named CRESEnT (Circular RNA Expression for Stable and Enhanced Translation), improves both mRNA stability and protein production efficiency.
The technology was found to increase protein production by up to 5.95 times and intracellular mRNA levels by 3.95 times compared to a control with no circularization. The enhanced mRNA stability is crucial for cell factories, as it allows for continuous production of desired compounds, such as biofuels, chemicals, and pharmaceuticals.
The researchers achieved circularization by rearranging the front and back portions of an intron in reverse order, allowing the mRNA to self-splice and reconnect inside the cell. Two design principles were identified to improve CRESEnT efficiency: optimal lengths for untranslated regions (UTRs) and a mechanism to help the intron fragments bind precisely.
The optimized CRESEnT system was tested in various microorganisms, including Escherichia coli, Bacillus subtilis, and Corynebacterium glutamicum, demonstrating its applicability as a platform technology for industrial microorganisms.
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