DNA origami!

03 April 2016

Interview with

Kerstin Goepfrich, The University of Cambridge

Origami, the ancient art of paper folding, is popular all over the world as a way of Origami Frogsrelaxing or expressing creativity. But a new type of origami which is making waves in science celebrates its 10th anniversary this year - Georgia Mills has the story...

Georgia - Scientists in Cambridge are currently using origami to make structures which could change the face of drug delivery.  There's just one twist - it's not paper they're using...

Kerstin - We are assembling DNA into arbitrary two and three dimensional shapes on the nanoscale.  So we are literally building with the building blocks of nature, so to speak.

Georgia - That's Kerstin Goepfrich who's working on this technique at the Cavendish Lab in Cambridge and she kindly agreed to show me around.  But first, I wanted to know why anyone would want to use DNA to build with...

Kerstin - What makes DNA a good building structure is, first of all, it's availability.  It's safe to use, you get it everywhere; it's very cheap and it's very easy to process; it's quite stable and we can programme it's assembly and that's, of course, the big plus.  You can programme assembly with near atomic precision.  So how do you fold a piece of DNA?  

Let me take out a piece of velcro tape actually, because I really like to use that for illustration.  So imagine, you had a long piece of velcro tape which is basically a long single strand of DNA - it's very floppy.  But now, imagine you had a short piece of DNA (a short piece of velcro tape) which matches the long one at one side and say at a distant end.  By doing that, you can pull the long piece together and now you've got something like a loop just made from velcro tape.  Now with many short pieces of velcro tape you could, essentially, fold the long piece up into any shape and here this is a bit, broken, but you will see you can make a flower or a clove by attaching a few pieces of velcro tape together and this is exactly how DNA origami works.  You take a long single strand of DNA and fold it up using short pieces, which we call staples.

Georgia - The four letters that form DNA (A, T, G and C), they like to stick to one another.  G always stick to C and A always sticks to T, and these are known as the base pairs.  So if you use this knowledge, you can design sections of the DNA strand that will always like to stick to one another and this would make the DNA automatically fold up on itself which can be used to build any structure you like.  So, if I wanted to fold some DNA into the origami classic shape of a crane, how would I go about it?

Kerstin - Today you just go online, you download a programme which is actually available for free and this programme is just a 3D drawing software so you literally draw  the shape you want.  So, you can literally draw a single strand of DNA and then it appears in the 3D view...

Georgia - Once Kirsten has drawn the right shape, she sends off the specifications to a company who then synthesise the DNA with the right pattern of base pairs needed.  They then send it back to her in a small white box which can then be processed in the lab...

Kirsten - This is the DNA room and, as you can see, it's not very exciting.  There are lots of fridges and freezers, which we use to store the DNA, and I will go to one of those now and I'll show you the little box in which the DNA comes...

Let me see... here.  And in every single one of the wells here we've got one DNA sequence and now we can take a pipette and we would use this pipette to mix all the difference sequences together, essentially...

Georgia - This is like no pipette I've ever seen.

Kirsten - Oh, this has 12 tips so that you don't have to do them one by one, we just get 12 at the same time.

Georgia - You're so busy here you need 12 in 1 pipettes?

Kirsten - Yes. We don't have a pipetting robot yet!  So, once we've mixed all the bits and pieces of DNA together, we put them in a small tube like this one here and then we put them into this machine, which looks fancy, but all it is an oven.  It's called a 'thermocycler' but it just heats the DNA up, cools it down slowly and then as it cools down it forms the predesigned shape.

Georgia - Why does heating it up and cooling it down help the individual strands form into whatever shape you've made?

Kirsten - You just give it a bit of energy so that when the DNA is already coiled up a bit it can straighten out and by cooling it down, you allow the DNA double helices to form.

Georgia - After seeing the lab I was satisfied I knew roughly how to make a DNA crane. What I wasn't clear on was why anyone would want to do this...

Kirsten - This is a great example of how something which might seem like art and a scientist playing around can be transformed into something real and into something which does have applications in the real world.  So, it is simply a way of assembling atoms with near atomic precision and, in my lab, we're using DNA origami to make small channels or pipes which can punch holes into membranes and into the envelope which surrounds the cell, and we are doing that because 50% of the drugs that we currently use target channels in cells.  So just imagine what you could do if you could could create artificial channels exactly the way you want them.

Georgia - So it will be a way of drug delivery?

Kirsten - It could be a way of drug delivery.  It could be a way of simply understanding the process which is really fundamental in biology, namely the way cells communicate.

Georgia - As well as potential medical applications, the technique has also be used to build tiny basic computers and also nanoscale rulers.  And, while paper origami is hundreds of years old, DNA origami celebrates it's tenth birthday this year.  So new possibilities for applications are still being dreamt up and, as far as Kirsten is concerned, the sky's the limit.

Kirsten - I think one day origami might even save a life which is what paper origami artist Robert Lange once said.  One day I hope the same may be true for DNA origami in a way.

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