The Short Version

The answers within us: Programmable DNA shapes and the future of biotech

Episode Summary

Arun Richard Chandrasekaran, assistant professor of nanoscale science and engineering at UAlbany, discusses how his lab is using synthetic DNA building blocks to construct nanoscale structures capable of assembling themselves into shapes specially designed for applications in medicine and nanotechnology.

Episode Notes

The longer version: 

In this week’s episode, Arun discussed how DNA nanostructures can be used for biotech as well as data storage. We asked about other applications being explored in the broader field of nanotechnology. As it turns out, materials science is fertile territory. There’s also growing interest in developing DNA barcodes.

ARC: Imagine a store where vegetables, produce or other plant or animal-based food items, all of which contain DNA, could be scanned using the DNA sequence within the item itself in lieu of a sticker. Why would this be helpful? Well, for one thing, this is an example of developing an alternative material, in the sustainability sense. Globally, we’ve already used up more materials than we should, so DNA is an alternate material that doesn’t cause environmental harm. And, since DNA is biodegradable, we don't have to worry about creating even more waste, or removing something that contains chemicals from our food before we consume it. These stickers might not seem like a big environmental problem, but they are made of plastic and glue and chemicals, so if we can use a different material instead, especially one that’s also biocompatible, that could be a good thing. And it’s not just about stickers; the bigger point is exploring DNA as a sustainable material that could potentially benefit other applications. 

I’m still picturing a futuristic grocery where you fill your cart, walk out the door, and everything is scanned, priced, and paid for automatically… 

ARC: So, yes, that’s the literal “barcode” connection. We can also extend the concept to disease diagnostics, though here the “barcode” becomes more of a visual signifier than a traditional barcode as we know it. 

For example, consider a strep throat or pregnancy test where the result readout consists of one or two lines to indicate positive or negative. I mentioned before how DNA data storage operates in binary – 1s and 0s – so we can use this system to indicate a positive or negative result for a given condition. This is something I worked on previously with Ken Halvorsen at the RNA Institute. We created a DNA-based assay where the result is a series of vertical lines, and each line encodes for a specific disease biomarker. The reason we did this is because we wanted to create a test to detect more than one biomarker or more than one disease in a single go. This could be especially helpful for DNA or RNA-based diseases which often require a complex assessment of multiple biomarkers to make a diagnosis. The readout for our assay took the form of five or six lines, each line representing presence or absence of a particular biomarker. Those lines, together, resembled a barcode. 

When it comes to creating DNA shapes, it doesn’t sound like much is off the table design-wise. For one, you mentioned DNA bunnies. What gave rise to the nano rabbit? 

ARC:The nanoscale bunnies were first made in Bjorn Hogberg's lab at the Karolinska Institute in Sweden in 2015. At the time, it was the first demonstration of making mesh-like structures using DNA and played a key role in advancing the technology that we’re working with today. (This Science Friday episode explains more.)

Go deeper:

So, nano means small. Like really, really small. It takes trillions of DNA nanostructures to form a 3D DNA crystal, which only becomes possible to see with the help of a microscope. Take a look at some examples of DNA crystals from Arun's lab.

Arun mentioned his soft spot for pop culture references in academic works including journal titles (this one’s for the Potter fans). He even wrote an op-ed on the topic, published in the journal Matter. As for how to use a movie reference to help science make sense? Arun's own Fifth Element connection passed peer review muster. 

One of Arun’s first paths of nano-exploration as a grad student focused on studying DNA’s “handedness”. Learn more about what that means, and how it recently led Arun’s team to challenge long-held truths about the structure of DNA.

Together with UAlbany’s Associate Professor of Biology Cheryl Andam, Arun initiated the “Goggles and Galleries” science + art event series late last year. Check out student artwork on display at that event. You can also view a gallery of Arun’s journal cover art here.

Take a look inside Arun’s lab at UAlbany’s Life Sciences Research Building and learn more about his research and art.

Episode credits:

Audio editing and production by Scott Freedman 

Photos by Patrick Dodson 

Interview and written by Erin Frick

Episode Transcription

Erin Frick: 

Welcome to The Short Version, the UAlbany podcast that tacklesbig ideas, big questions, and big news in less time than it takes to cross the Academic Podium. I'm Erin Frick in UAlbany's Office of Communications and Marketing.    

Arun Richard Chandrasekaran:

People are familiar with the concept that DNA is part of biology. It's in every cell and that's where we get the hereditary traits from. DNA is made up of four building blocks that we call nucleotides or bases. We can make DNA in-house using these four building blocks. And the idea is that using the programmable based pairing, we can now put together these DNA strands to make different nanoscale structures that we want.

Erin Frick: 

These days, you can buy anything online. That much isn’t new. But did you know that “anything” includes synthetic forms of the biological building blocks that make up every living thing? Yes. Nucleotide bases. If this term rings a bell, your mind might have just conjured a flashback to some early science class where you linked colorful mini marshmallows with toothpicks to form the ladder-like “double helix” structure of DNA, the blueprint that makes humans, and all other forms of life, possible.

In the model I just described, the marshmallows are the nucleotide bases. Four different bases make up DNA. Formally, these building blocks are called adenine, thymine, guanine, and cytosine, but even scientists usually call them by their nicknames: A, T, G and C. 

These letters make up the code that tells cells what to do — like how to replicate or perform the functions that keep us alive. But, these bases aren’t just a code, they’re also a physical material capable of storing vast amounts of information.

Because A always pairs with T and G always pairs with C, these bases can be programmed beyond the double helix to create any number of intricate DNA shapes. Stars, triangles, lattices, you name it. These tiny structures are like DNA origami, but instead of folding paper squares to create boats and cranes, scientists like assistant professor of nanoscale science and engineering Arun Richard Chandrasekaran are exploring new ways to mold DNA bases into structures designed to perform a particular task, like delivering medicine to a targeted part of the body. 

Key to this work is something called DNA self-assembly— that is, leveraging DNA’s predictable base pairing to instruct the building blocks to arrange themselves into precise structures with the help of special chemical solutions and temperature.

What could this be used for? Lots of things. For example, someday, this technology could be a new way to package drugs, diagnose disease, or even store data. 

I sat down with Arun to learn about how exactly his lab is building DNA nanostructures and the new scientific frontiers being explored at the intersection of biology and nanoscience. Arun is also a digital artist and a writer, so we touched on those passions too, and how they overlap with his science. 

Here’s our conversation. 

Erin Frick:

How did you become interested in studying DNA nanostructures? How did you get your start?

Arun Richard Chandrasekaran:

I was doing my master's in nanoscience at the University of Madras back in India, which is where I'm from. And during my master's, I had a course in biophysics. I thought this was really cool the moment I heard about it. I also happened to work on crystallizing Z-DNA molecules for my master's project. These are left-handed DNA molecules, which is in contrast to the usual right-handed DNA we are familiar with. And that gave me an introduction to the field and that's where I became interested and I sort of knew I wanted to do a PhD and it narrowed my focus towards DNA nanotechnology. And then I applied for my PhD in several schools. I got into NYU. It was my first yes, from any school and the rest is history. 

Erin Frick:

What brought you from NYU to UAlbany?

Arun Richard Chandrasekaran:

So at NYU, my PhD work was mostly on the design of DNA nanostructures, especially self-assembled crystals. And towards the end of my PhD, I really loved the field, so I wanted to explore more, or at least stay in the field for a bit. I also wanted a slight change to move from design and assembly into more applications. Ken Halvorsen at the RNA Institute, he had just begun his lab. I was his first postdoc, and he was developing these DNA nano-switches and the idea was to detect different biomarkers. At the time, our primary focus was to detect different micro RNA sequences, and these are sequences in the body that could, by their change in levels, could affect certain disease processes. I really liked the place and Ken's lab and I interviewed and it brought me more towards the application side of things in DNA nano.

Erin Frick:

What is a DNA nano structure? How do you make them, and what are you studying in your lab?

Arun Richard Chandrasekaran:

Currently, the field focuses both on assembly and applications. In our own lab, we are focused more on the assembly. We make different types of nanostructures. These can range from simple cubes to more complex structures. For example, a nanoscale bunny that is made entirely out of DNA. Then the question is, okay, it's so cool, but so what? We are trying to explore the applications part of it, some of which include drug delivery applications, diagnostics, and so on.

Erin Frick:

You listed a couple interesting applications there. Let's just start with drug delivery. Could you break down how a DNA nanostructure would be used for drug delivery, what that process would look like and why would it be better than current systems?

Arun Richard Chandrasekaran:

A couple of key advantages of using DNA for drug delivery, is that DNA is a natural material, so it's already in the body, so it's biocompatible. We don't expect any adverse effects from using DNA as a drug delivery carrier. And this has also been shown experimentally in a few studies. And two, we can functionalize the DNA nanostructures to include several different modifications. For example, you could make a DNA nanostructure open or close in response to light. So now you could imagine you deliver a DNA nanostructure and only when you shine light of a particular wavelength, the structure opens up and it could release whatever cargo you want to release at the tissue.

Erin Frick:

Something else that you mentioned before is that these could also be used as a diagnostic tool.

Arun Richard Chandrasekaran:

Since DNA is a biological material, diagnostics and drug delivery have been the major focus of several labs, including my post-doctoral lab here at UAlbany in the lab of Ken Halvorsen. So yes, DNA nanostructures have been very much used in biosensing and diagnostics. And these could include a variety of biomarkers. Biomarkers are molecules in the body that change level. Once we have a disease, the level could go up or down. And by finding out these changes, the idea is that we can diagnose a particular disease for each biomarker. It'll change its shape, but then the shape would be slightly different for each biomarker, which is what gives us a different readout. 

Erin Frick:

Something that you are looking at is nanostructure self-assembly and there are particular conditions that need to happen in order for that to occur. What are the particular conditions that need to happen to facilitate self-assembly? What are you looking at?

Arun Richard Chandrasekaran:

In our lab, we do currently focus more on the assembly side of things, and there are two important factors we are trying to focus on. One is the assembly process itself. Typically, when we make these structures, we mix together different DNA strands that form the structure. You heat it up and then cool it down over a range of time. We are trying to see if these structures can be made at constant moderate temperatures. So here, the idea is that you mix these strands, but instead of heating up and cooling it down, you just let them sit at a particular temperature. We think that this opens up the DNA nanotechnology process itself because we've now eliminated the use of a thermocycler or heating block. The second aspect is can we make these structures more stable? And the stability we are focusing on is called biostability wherein we see how these structures survive in physiological conditions and we could mimic it in solution, for example, by putting these structures in serum or other bodily fluids. And we found that by changing the assembly conditions, we can also modulate the biostability. While assembling these structures, we also take into account the design of the structure itself, and these structures that are more tightly packed tend to be more biostable, meaning they can withstand bodily conditions much better.

Erin Frick:

This idea of the nanostructure self-assembly and this concept of that happening in the body, how does that actually work? What is the input that is somehow put into the human body that allows you to have the components for a nanostructure to self-assemble and go off and do a job?

Arun Richard Chandrasekaran:

Most, if not all, of the stuff we do in the lab is outside the body. So, even if the DNA and the proteins that we use are biological molecules, everything is synthetic. So, we do everything outside the body. However, some of the advances, for example, these structures being able to assemble at a constant temperature, all lead to potentially making these structures in vivo, that is, inside the body or a cell. The major step towards achieving that would be to use sequences that already exist in the body instead of designing our own. So, if you can use a sequence that already exists in the body, you can now include complementary regions or complementary DNA and RNA strands which help these structures fold in a physiological system, for example, inside cells. And in some cases, this could be a gene which is now folded and prevents the gene from performing its function, thereby preventing a disease. Or it could be the opposite where things that are already bound to a gene are now relieved and then the gene is more accessible to do its function, thereby reducing the disease.

Erin Frick:

We tend to think of nanotechnology in terms of hardware, so things like semiconductors and computer chips, but really, it describes all technology operating at the nanoscale. How much overlap is there between biotech and nanotech, and where do you see the most promising areas for advances at this intersection?

Arun Richard Chandrasekaran:

There's definitely overlap between the hardware side of nanotechnology and DNA nanotechnology. The most prominent or the blossoming area is in data storage. There are several groups which have done DNA-based data storage, and typically the idea is we encode information in the DNA sequences and then eventually you can create a library of DNA sequences, which you can then read out using a DNA sequencer. The reason people started looking at it is because digital data, as we know, is almost doubling every two years, and there's only so much cloud space or server space we have to store. Companies like Microsoft and Western Digital who make these hard disks have invested money in DNA-based data storage. And that's where the actual overlap between hardware and DNA based software comes in.

Erin Frick:

What kind of data are we talking about when we're talking about using DNA to store data? Could you give some examples?

Arun Richard Chandrasekaran:

Sure. All data, you could break it down in simpler terms to binary zeros and ones. In simple cases where you want to include, let's say a sentence, you could break it down into ones and zeros, and you could encode it into a string of DNA characters. And DNA is made up of the four nucleotide building blocks. And now if you imagine a hundred nucleotide long DNA strand, and you can now imagine a pool where you contain 10 million DNA strands, all of which provide more depth of information storage. And what has been done so far is encoding information such as paragraphs, textbooks, and even musical notations within DNA. And this can be read out typically using sequencing methods.

Erin Frick:

Obviously this isn't a USB or a floppy disc or something. How do you access data that's been stored in DNA?

Arun Richard Chandrasekaran:

This would be more like a small tube which contains DNA in a solution or if it's dry. And then there's a method called DNA sequencing where you can read the sequence of each piece of DNA that you have and you can now work back what type of information you encoded in a particular string of characters. For example, if A T C G encodes the letter A, then if you sequence back out A T C G, then you can say, okay, this is an A, and so forth. It is still tedious as of now, but going forward, I think there are several advances that have made the process much cheaper, and I believe it'll be more accessible in the future.

Erin Frick:

Outside the lab, and maybe inside too, I know that you're an artist. What medium do you engage with, or media, and do you ever see crossover between your science and your art?

Arun Richard Chandrasekaran:

A lot of times. I like science-based artwork. Nowadays, I'm more on the digital side. I use digital illustration software to create science-based artwork, and typically one forum that we can relate our work to the public or general audiences through journal cover artwork. We've had several successful covers in journals, and I also encourage people in my lab to do it. So we had a former undergrad who painted a DNA-based sweater that eventually landed on the cover of a well-known journal, and she was also the first author in that publication. And I also love using pop culture references both in my articles as well as in my presentations. I try to make an analogy to pop culture references that people may connect with. And I think people remember these better than the science, and I've at least met one person who said, oh, I remember this slide where you had this movie reference. So even if they did not understand the scientific concept, they at least were able to remember the analogy and knew something about DNA. 

I also wrote an article about using pop culture references in scientific articles, so I like doing those things. Recently with Professor Cheryl Andam, who's the director of the life sciences, we started something we call “Goggles and Galleries” where we try to bridge science and art. So, we had an exhibit back in December ‘25, and we plan to make it an annual event where we invite all the students, faculty, anyone who's in UAlbany to bring forth your artistic work that is science related or science adjacent. And we hope to bridge the sciences and the art world more going forward.

Erin Frick:

Why is it important to communicate science and research to the general public?

Arun Richard Chandrasekaran:

There's a disconnect between the way we do science and talk science inside, for example, the department or between faculty, and the way we talk science to the general public. So, I think it's important for scientists to communicate what we do to the public, and that's one primary reason why I do science communication. And I try to participate in events like the “Capital Science on Tap,” where a group organizes events in a bar or a local restaurant and the public can attend and discuss science. So, I think as scientists, it's part of our job to communicate the science we do. And a lot of time we think we are communicating it, but then there's a lot of jargon or the types of words we use may not actually relate to the general audience. So, we have to break it down and convey it in a way that people will understand.

But I also try to tell my students, when you're presenting, it's not for you, it's for your audience. So, I try to bear that in mind too. When we do science communication, things are more casual. And even within University at Albany, for example, I think it motivates or encourages students to be part of research if they hear something like a pop culture analogy. For example, I speak to the Living Learning Community for the World of Chemistry every year. I think it encourages them to at least start a discussion with faculty about what type of research they do, how they can be a part of it. And keeping it casual, I think, breaks the barriers for early-stage students and high school students to be part of the research early on.

Erin Frick:

That was Arun Richard Chandrasekaran, Assistant Professor of Nanoscale Science & Engineering at UAlbany’s College of Nanotechnology, Science, and Engineering.

In this week’s episode, Arun described how he and his team are programming synthetic bits of DNA to self-assemble into nano-scale structures designed to perform distinct jobs in applications ranging from biotechnology to data storage. 

To learn more about Arun’s work, including the importance of studying DNA’s “handedness” — yes, as in left or right; how his technology could one day be used to scan produce at the grocery store; and to see psychedelic photos of what these structures look like under a microscope, check out The Long(er) Version, in our show notes. 

The Short Version would not be possible without contributions from many people, including, for this episode, Scott Freedman, who provided audio production and editing from the UAlbany Digital Media studio deep inside the Podium tunnels.   

We’ll be back next week with another short conversation about something interesting.