RNA molecules can be folded into complex molecular machines. Inspired by natural RNA machines, researchers at Aarhus University in Denmark developed a method called “RNA origami,” which makes it possible to artificially design nanostructures folded from a single RNA scaffold.

The research paper, published in the new issue of Nature Nanotechnology, describes how RNA origami techniques are used to design RNA nanostructures characterized by Danish cryo-electron microscopy (Cryo-EM). Using Cryo-EM, researchers were able to fine-tune molecular designs to build increasingly complex nanostructures.

An RNA cylinder sample contains two very different shapes, and by freezing the sample at different times, a shift between the two shapes becomes apparent. The researchers observed this transition in real time and found that the folding transition occurred after about 10 hours. The researchers identified a phenomenon known as a “folding trap,” in which RNA is captured during transcription before it is released.

Researchers say the folding is usually done in less than a second, and it’s surprising that RNA molecules fold so slowly. They hope to be able to use similar mechanisms to deliver RNA therapy to patients at the right time and place.

Inspired by the Hubble Space Telescope, the team combined RNA rectangles and cylinders to create a multi-domain “nano-satellite” that can explore the folded space of RNA and determine the 3D structure of individual particles using electron tomography.

This research into the origin of RNA will help improve the design of RNA molecules for use in medicine and synthetic biology. In the future, researchers from computer science, chemistry, molecular biology, and microbiology will be able to design, model, and measure folding at higher temporal resolution.