RNA Origami – The 6 Helix Bundle

Hello everyone! I am Néstor Sampedro, you may remember me from other blog posts like Meet Néstor Sampedro…

Pretty cool things are being designed with DNA, so first of all, make sure to check out the previous exhibition from Rafa about Dynamic DNA Origami. But, unlike the rest of our friends in the DNA Robotics Network, we work with RNA instead of DNA.

RNA can also be used to build pretty cool structures, and the good thing about RNA is that it can be encoded on a gene!

200115_Nestor 1 — The RNA polymerase reads the information written on the gene and produces the respective RNA, that folds into the desired shape

Imagine genes that have the information to build synthetic machines in our bodies! … We are not there yet… but quite close, so today I will give you a brief introduction to how we do RNA design.

The 6-helix bundle is one of my favorite structures because it is built in 3 dimensions. When we design RNAs, we look at what nature has done so far and we can find very interesting motifs that act as Lego building blocks that we can piece together into cool shapes. We take those building blocks and combine then in a specific way to build our structure.

6HB_spinmovie — This is a 3D model movie of our design generated by the computer. With only 4 different motifs that we find in nature it is possible to build a 3D structure like the 6-helix bundle. See the 4 motifs in the figure below.

That’s the designing part. Then we want to make sure that this modelling looks right in real life so we take this to the lab and characterise it with some very powerful electron microscopes.

200115_Nestor 3 — With only 4 different motifs that we find in nature it is possible to build a 3D structure like the 6-helix bundle. These bundles are just below 20 nm long, scale bar is 100 nm.

Our 6HB above are fixed with a negative staining to be able to be seen under the electron beam, so they are quite steady, but that is not how they are in solution, that is very hard to see. However, there are some nice computer tools that help us simulate how these structures behave, my fellow Joakim Bohlin has written a nice blog post about how we can use the computer to get a better grasp of our designed molecules, so I will leave here a little movie made with oxRNA.

oxRNA_6HB — A simulation of a 6-helix bundle made out of RNA. These devices are actually quite floppy and this is an approximation of how they would look inside a cell!

Now, why is it cool to build these kinds of stuff? What can we use it for? Well, think of a structure like this as a scaffold, to which we can integrate different functional motifs to create our genetically-encoded nanomachines.

Stay tuned to see how this and other projects develop, new post from my fellows will come up soon, don’t sleep on them!

Néstor Sampedro, PhD Student at Aarhus University