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Our DNA stores the information that makes us who we are, but that's not all it can do! There are applications for DNA that go way beyond its use for life, like storing data and folding it into complicated shapes.

Hosted by: Stefan Chin

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Sources:
Biological computers
https://www.scientificamerican.com/article/dna-data-storage-is-closer-than-you-think/
https://escholarship.org/uc/item/004485qm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714485/
https://news.mit.edu/2016/programming-language-living-cells-bacteria-0331
https://www.sciencemag.org/news/2017/03/dna-could-store-all-worlds-data-one-room
https://science.sciencemag.org/content/355/6328/950
https://jbioleng.biomedcentral.com/articles/10.1186/s13036-019-0211-2

Aptamers
https://www.basepairbio.com/what-is-an-aptamer
https://pubmed.ncbi.nlm.nih.gov/21720957/
https://www.frontiersin.org/articles/10.3389/fmolb.2018.00041/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704523/
https://www.bausch.com/ecp/our-products/rx-pharmaceuticals/rx-pharmaceuticals/macugen-pegaptanib-sodium-injection
https://www.annualreviews.org/doi/pdf/10.1146/annurev-pharmtox-010716-104558
https://pubs.acs.org/doi/10.1021/acs.accounts.9b00167
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730239/
https://www.frontiersin.org/articles/10.3389/fchem.2020.00434/full

DNA origami
https://pubs.acs.org/doi/10.1021/acssynbio.0c00235
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543475/
https://www.idtdna.com/pages/education/decoded/article/practical-applications-of-dna-origami
https://www.nature.com/articles/s43586-020-00009-8
https://www.sciencedirect.com/science/article/abs/pii/S0927796X19300427
https://www.digitaltrends.com/cool-tech/dna-origami-allows-for-3d-printed-dna-bunnies-to-deliver-medication/
https://www.jhunewsletter.com/article/2020/02/dialogues-in-research-dna-origami-and-labyrinths
https://pubmed.ncbi.nlm.nih.gov/24963790/
https://pubmed.ncbi.nlm.nih.gov/26988942/
https://scitechdaily.com/dna-origami-used-by-mit-engineers-to-identify-vaccine-design-rules/

Nanomanufacturing
https://www.nature.com/articles/natrevmats201768
https://science.sciencemag.org/content/368/6493/878.full
https://engineering.stanford.edu/magazine/article/stanford-scientists-use-dna-assemble-transistor-graphene

Images:
https://commons.wikimedia.org/wiki/File:DNA_animation.gif
https://commons.wikimedia.org/wiki/File:German_microdots_World_War_II_Mexico_Spain.jpg
https://commons.wikimedia.org/wiki/File:Aptamer_biotin.png
https://commons.wikimedia.org/wiki/File:Base_pair_GC.svg
https://www.eurekalert.org/multimedia/pub/135765.php?from=353525
https://www.eurekalert.org/multimedia/pub/242138.php
https://www.eurekalert.org/multimedia/pub/84649.php?from=285507
https://www.nature.com/articles/micronano201772/figures/5
https://commons.wikimedia.org/wiki/File:DNA-AuNP0022.jpg
https://commons.wikimedia.org/wiki/File:Transbauformen.jpg
https://www.eurekalert.org/multimedia/pub/242287.php
https://commons.wikimedia.org/wiki/File:Graphen.jpg
https://commons.wikimedia.org/wiki/File:Kohlenstoffnanoroehre_Animation.gif
https://commons.wikimedia.org/wiki/File:DNA_nanostructures.png
https://commons.wikimedia.org/wiki/File:Dnaconformations.png
[♪ INTRO].

Good old deoxyribonucleic acid. You might hear ‘DNA’ and think, ‘the blueprint of life.’ And while, yes, our DNA stores the information that makes us who we are, that’s not the only thing it can do.

A quick primer on

DNA: If you think of DNA as a molecule, it’s this iconic twisted ladder made of two strands that join together down the middle. Each strand is a long chain of building blocks called nucleotides, which have a sugar, deoxyribose, that creates the backbone of the strand along with another chemical called phosphate, and a nucleic acid that sticks off to the side and makes half of a rung of the ladder. And that’s how you get the name deoxyribonucleic acid, DNA. There are four nucleic acids, and each one has a buddy.

Adenine and thymine are one base pair, and cytosine and guanine are the other base pair. And that’s basically what you need to make this efficient, predictable system that stores the instructions to create a person in each cell, and can be passed down over generations. But some scientists and engineers have been looking at DNA and saying,.

Hey, what if we used that to, like, make some other stuff? Like DNA is predictable with its base pairs, relatively simple and we know all the building blocks, it can self-assemble, and biologists have already figured out how to manipulate it in the lab. It has lots of potential.

So here are four ways that scientists and engineers are using DNA in new technology. DNA is often described as the code for life so biological computers treat it like, well, code. Biological computing refers to all of the ways that scientists can apply the principles of biology to the field of computer science.

That can mean using DNA for storing data, writing programs, and running those programs. When a computer stores data, the code is written in ones and zeroes, which get recorded in the physical hard drive by transistors, tiny switches that can be flipped on or off. But transistors rely on electrons to flow through them, and as the size of a transistor gets smaller, you start to run into the weird world of quantum physics.

And using DNA to store data could get around the size limits of silicon and electricity. Like, one transistor switches with ‘bits’ of data, the one or zero. But DNA has four nucleotides, so you can get more creative and efficient.

Because there are four ways to pair ones and zeros. So if you translate each nucleotide to a pair of binary digits, one nucleotide could theoretically store two bits of data. Although researchers haven’t quite reached that level of efficiency yet.

Scientists began testing DNA’s ability to store data in 1999 with a 23-character message. They treated it like a World War II-era secret message called a microdot and chose the message JUNE6 IN

VASION:NORMANDY. In 2017, researchers at Columbia University stored six large files, including an entire 1895 French film, in lots of small DNA fragments that could be reconstructed into one long chain. And their system had an efficiency of 1.6 bits per nucleotide. Data storage like this would probably be applied to archives, the kind of data that people want to store for a long time but don’t necessarily access every day.

But many of us do use computers every day, for a lot more than just storing data. Fundamentally, computers also receive inputs to process data, like a click for example, and then give outputs, like the display or audio. And biological computers are moving in that direction, too.

Genetic circuits rely on the same logic as computer circuits to process inputs, which could be a specific change in the environment, and DNA expression creates the outputs. A simple circuit might sense whether one chemical is present, and if it is, it could make a specific protein. This is an action known as a logic gate, a computer science term that usually refers to how circuits interpret and respond to electrical signals.

Some biological logic gates involve sensing many chemicals before making outputs from DNA. In others, the output is actually to block DNA expression. Stack them together, and you make a biocomputer program!

Researchers are developing programming languages so that you can write up your biological software on a computer, turn it into DNA sequences, and then stick it in some cells to make them do your bidding. The goal of all this is to make data storage and processing more space and energy-efficient. Which is to say, more like biology.

Now when we’re working at this microscopic scale, it would be really hard to go into a test tube and pluck out the exact molecule that we want. DNA can help in the form of aptamers. An aptamer is a short, single-stranded piece of either DNA or its cousin RNA, between 20 and 80 nucleotides long, that gets folded up into a shape that can stick to other things, like proteins.

And the shape of the DNA will dictate whether it sticks to what you want, but the shape needs to match just right, like Cinderella’s foot into her glass slipper. But chemically, nucleotides have a lot going on that makes them stick to other molecules. Their ends can form hydrogen bonds, which is a magnetic-like attraction between an exposed hydrogen atom and a neighboring electron cloud.

These magnetic-like forces keep the DNA strand stable, by interacting with bases above and below, which is also called base stacking. When these characteristics come together, an aptamer is like super-specific velcro, so if it bumps into its target it’ll grab on. To design an aptamer, scientists most often use a process called.

Sequential Evolution of Ligands by Exponential Enrichment, or SELEX. You begin with a bunch of possible aptamer options, a library of short DNA strands that you hope might fit on the target molecule. Let’s say it’s a protein that looks like this.

You mix together your possible aptamers and target proteins. Sequences that stick to the protein will do that, and others will stay loose in the solution. Wash away those loose bits of DNA, and you’re left with protein-plus-DNA.

Then, separate the protein and DNA, and purify the DNA. The molecules left in your test tube should be pretty good aptamers. And by repeating this process a few times, you can narrow down your aptamers to the very best of the best.

Once you have a good aptamer, what can you do with it? Well, one way to use aptamers is as medicine. One of the first medical aptamers was designed to fight wet macular degeneration.

This is an eye condition that can cause blurry vision or a blind spot because of fluid buildup in the middle of the retina. The condition is caused by a chemical called Vascular endothelial growth factor. And when it attaches to a protein on the surface of a cell, it sets off a cascade of reactions that ends up creating new blood vessels, which then leak fluid into the retina.

But an aptamer, in this case made of RNA, can latch onto that Vascular endothelial growth factor like velcro and prevent it from causing trouble. But aptamers are kind of small. Let’s think bigger.

If you take a strand of DNA that’s 8,000 bases long, and fold that up into a specific shape, you get DNA origami. Like the Japanese art of folded paper, DNA origami is based on one super long, single-stranded DNA molecule, called the scaffold. But DNA is more stable when it’s double-stranded because of that nucleotide buddy system, base-pairing.

So, much shorter ‘staple’ strands that are more like 30 to 80 bases long are designed to match up with short sections of the scaffold. Half of the staple might match up way over here on the scaffold, and the other half might match way over there. So the staple can pinch the scaffold together, with a loop of single-stranded scaffold hanging out behind it.

If engineers do that to the scaffold a bunch of times, they can fold DNA like a wire sculpture. The attraction between nucleotide buddies is strong enough that these structures can self-assemble, mixing around in the test tube until all of the staples find their match on the scaffold and voilá: a bunny! But DNA origami isn’t just cute.

A major application of origami is in DNA nanorobots. But they’re not mini mecha-bots, like “Optimus 5-Prime-to-3-Prime.” Scientists are studying them as a way to deliver cancer drugs straight to tumors. A study from 2018 described them as robotic DNA burritos.

The origami in this case, is a rectangular sheet of DNA that gets rolled into a tube, held closed by an aptamer while carrying a drug in the middle. The aptamer on the DNA burrito is designed to stick to a molecule on the surface of cancer cells. And when the aptamer sticks to its target, it can no longer hold the burrito closed.

So the DNA origami unrolls, releasing the drug to fight the tumor. But DNA does more than just folding; it’s one of the tools in nano manufacturing, the creation of nano-scale structures. Nano manufacturing combines DNA with lots of different small-scale materials, like metal.

It all started in 1996, when scientists first combined gold nanoparticles with short pieces of single-stranded DNA. When the complementary DNA strands were added to the gold mix, the DNA doubled up because of the buddy system and it pulled the pieces of nano-scale gold along with it. So nano manufacturing takes advantage of DNA’s ability to self-assemble as a way to combine tiny, non-biological materials into their final forms.

So this is where everything comes together. Remember transistors? Well, right now, they’re made of silicon, but carbon nano materials are in the running for next-generation transistors.

There are two major kinds of carbon nano materials :. Graphene, which is a single-atom-thick sheet of carbon that looks kind of like honeycomb, and carbon nanotubes, which is what you get when you roll that sheet into a cylinder. And researchers are testing both of these as replacements for silicon transistors.

But when you’re trying to engineer with something so extremely small, you can’t really go in with tweezers and, like, move stuff around. You have to get creative. In 2013, scientists used DNA as a template.

They created straight lines of DNA, and by adding copper and methane, they released carbon atoms from the DNA that then attached with each other to create graphene ribbons, which could then be used in tiny transistors. And in 2020, a team of scientists in China showed that they could put carbon nanotubes for transistors precisely where they wanted them by using DNA origami bricks. In this case, the DNA origami are folded into dozens of unique bricks that specifically attach to only a few other bricks or DNA sequences, so that engineers can plan ahead for what bricks and sequences to use.

So the researchers created a template of DNA origami bricks, and wrapped their carbon nanotubes with matching single strands of DNA. In a feat of self-assembly, the nanotubes found their bricks with precision down to 10 nanometers! But the origami bricks aren’t the final product, just a part of the manufacturing process.

The DNA interferes with the transistor, so it gets washed away leaving the nano-scale structures in place. So from storing data to folding into complicated shapes,. DNA has a lot of potential beyond the blueprint of life.

Thanks for watching this episode of SciShow! We have made thousands of educational videos over the years, and we’ve been able to offer them for free because of our patrons on Patreon. So, to all our patrons, thank you for what you do to make SciShow happen.

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