Translating modern RNA nanotechnology innovations in the biological context possesses immense potential due to compatibility with folding and expression in cells, but it also imposes unique challenges such as tight performance conditions and inherent instability of RNA molecules.

However, a recent structural RNA design approach developed in the Andersen lab, termed "RNA origami," is trying to tackle this. This approach attempts to generate complex man-made RNA-based devices that are stable in cells, interact with other biomolecules, including other RNA and proteins, and enable unique applications, particularly in the context of gene regulation.

Demonstrated by two distinct approaches recently published in Nucleic Acids Research, RNA origami is presented as a sophisticated RNA design platform that, when applied in the cellular context, generates unique molecules for synthetic biology-based regulation.

RNA sponges regulate enzyme production in bacteria

In the first approach, the RNA origami was used to achieve precise control of protein production levels when expressed in bacteria. Self-inhibiting protein expression cassettes were made by installing a strong binding site for the expressed protein in its own gene. Afterwards, RNA origami decorated with the same protein-binding sites was expressed in large excess.