Programming with DNA origami?

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Today we are back at looking at some cool DNA origami applications! What if we could use them to compute information? Read ahead to learn more! And don’t forget to share with a friend if you think they might like it.

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Programming with DNA origami?

As we have seen a bunch of times, and most recently in our series about protein nanocages, self-assembly is a fundamental aspect of nanotechnology: small components can autonomously organize into larger, well-defined structures. Researchers have drawn inspiration from natural processes, like the formation of viral capsids, to create structures that have the potential to revolutionize entire fields, such as drug delivery and biosensing. My personal favorite tool for nanoscale assembly is DNA origami, hands down. A single, long stranded scaffold is folded into nanoscale shapes by short single stranded staples: self assembly at its best. In addition, DNA origami structures can also combine to make even bigger structures (we covered a cool new strategy here). Some of the approaches used, though, have limitations:

• Often, they rely on environmental queues for assembly, like pH or temperature, which can be hard to program properly.

• Most of these systems are not very versatile: they can’t be used to create diverse shapes or implement a wide range of instructions using the same building blocks.

This brings us to today’s paper, which offers a solution to these problems. The authors introduce a new type of DNA origami building block: these structures look like 3 connected crosses, and can be visualized as 1 × 3 2D rectangular units. What makes them special is the presence of 8 programmable edges, which allow flexible and (this is important) customizable interactions. Each edge can be independently programmed to bind other structures, using different DNA strands as molecular instructions. Each instruction is encoded in an instruction field, which include:

• Connection field: Specifies which edges will interact.

• State field: Controls how the edges connect (more on that later).

• Code field: Ensures distinct binding sequences, preventing unintended connections.

Each edge operates in one of three modes:

• Off: DNA hairpins make the edge inert, so it doesn’t interact with anything.

• Deterministic: Sticky-ended DNA strands ensure precise, programmable connections.

• Non-deterministic: Stacking interactions allow edges to bind randomly, adding flexibility to assembly.

Using these programmable DNA origami building blocks, they showed the assembly of different 2D arrays. They started with two DNA origami tiles: they demonstrated the creation of 12 distinct arrays, with a total of 48 different array possible! Pretty cool, if you want to program something. But they then moved into even more complex assemblies: they presented square frames, long strips and even a windmill! All of these structures were characterized using atomic force microscopy and transmission electron microscopy.

The authors didn’t just stop at making complicated shapes: the coolest part is the implementation of a logic gate. From Wikipedia, a logic gate is a device that performs a logical operation that take one or more binary inputs and produces a single binary output (this is a Boolean function). In the paper, the researchers constructed two logic gates:

• AND Gate: Output structures formed only when both input instructions were present.

• XOR Gate: Output structures formed only when one input was present but not both.

A very interesting idea! This was a fun paper to read, and it can have some interesting applications:

• Molecular computing: Of course. These building blocks could be used as a base unit for programmable nanocircuits.

• Nanofabrication: The programmable assembly of DNA origami can open new avenues in nanoscale materials and devices (DNA origami-based electronics when?)

• Biosensing: Systems like this could be used to sense biomolecules, such as RNA or other markers, by adding functional components like aptamers.

So, if you are interested, just go and read the paper here! It’s a cool one.

And as always, thanks for reading!

In other news:

• Trapping proteins in DNA cages: If you like nanocages but DNA is more your thing, run to read this paper. Here, the authors present a multistage reconfigurable DNA nanocage capable of capturing and regulating proteins through reconfiguration. The nanocage transitions between pyramid, square, and linear shapes, enabling precise control. The authors show the ability capture thrombin and regulate its activity. Quite interesting!

• Science’s breakthrough of the year: For something a bit different this time, this article covers what Science (the journal) decided was the biggest breakthrough of 2024: lenacapavir. This is a new, injectable HIV drug that targets the capsid and had an astonishing 100% efficacy in a first trial in Africa, and then a 99.99% efficacy in a trial after that. This is amazing news, and opens the possibility to final curb the HIV epidemic, and also opens the door for similar treatments for other viruses.

• Hinging on DNA origami: A sure way to make DNA origami more interesting is to add gold nanoparticles. But what is even better? When the DNA origami moves thanks to the gold nanoparticles. In this article, the authors introduce a DNA origami hinge enabling continuous pivot motion, controlled by DNA intercalator concentration.The hinge, made of two six-helix bundles linked by gold nanoparticles, offers tunable sensitivity and range of motion. Very cool!

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