DNA – More Than Just Genetic Material
As is widely known, DNA base pairing (Figure 1) provides the chemical foundation for the world of genetics. DNA is the hereditary material in humans and almost all other organisms. It contains the instructions needed for an organism to develop, survive and reproduce [1]. This establishes it as the primary building block of biology. DNA is talked about, mostly, in the context of this role. However, its use as the basis for the creation of new materials is gaining an increasing level of traction [4]. DNA and protein-based materials have vast potential as chemical tools for the synthesis of more advanced systems. This ultimately leads to the development of improved diagnostic and therapeutic techniques. It is this facet of DNA that Dr. Devleena Samanta from the University of Texas, Austin, explores at the Samanta Laboratory.
Figure 1: Specific base pairing in DNA
A base pair is a connection between nitrogenous bases that helps hold the two strands of DNA together. This connection essentially creates the rungs of the ladder in the DNA molecule. There are specific patterns for how the bases match together, called Chargaff’s rules. These rules explain that adenine always pairs with thymine (A with T) and cytosine pairs with guanine (C with G).
DNA Origami
One of Dr. Devleena’s research projects involves the technology known as ‘DNA origami’, a more recent technique that uses DNA for the synthesis of nanoparticles. Imagine the double-helix structure typically associated with DNA. Heating it results in the separation of the two DNA strands. The single strands thus obtained are utilised in the DNA origami method [4]. “Origami” is the Japanese art of paper folding, with the goal being to fold a flat sheet of paper into a finished sculpture. Similarly, these long strands of DNA are folded into a complex structure of “staple strands” which each have 200–300 nucleotides* [2].
The underlying principle behind DNA origami is based on a simple rule: base-pair complementarity. Generally, hydrogen bonds in DNA that pair the bases adenine and thymine (A to T), and cytosine and guanine (C to G) allow complementary DNA strands to form into a double helix spontaneously. However, if the two strands are only partially complementary, both strands can accept multiple DNA molecules and be folded into multiple different shapes [3]. Thus, DNA sequences are designed and folded onto themselves using the origami method. Here, the folded structures are held together using the aforementioned staple strands of DNA [4].
Applications of DNA Origami
The result is a vast array of structures of different complexities. Creating a map of the United States completely out of folded DNA is one of its more amusing applications. But DNA origami has the immense potential to contribute significantly in a wide range of fields, such as diagnosis and drug delivery. Cancer therapy is one such potential domain where it showed significant efficacy and may contribute immensely [2].
*A nucleotide is one of the structural components, or building blocks, of DNA and RNA. It consists of a base (one of four chemicals: adenine, thymine, guanine, and cytosine) plus a molecule of sugar, and one of phosphoric acid.
DNA Nanostructures: What’s So Special?
Structure and composition are the two main characteristics of a material that determine its chemical and physical properties. Graphite and diamond, for example, are both made of carbon – yet, graphite is slippery and soft while diamond is one of the hardest substances known to humankind. Similarly, the structure of DNA-based materials at the molecular level is what determines the properties they display.
A demonstration of the importance of molecular structure can be seen in the DNA nanostructures that Dr. Samanta works with in her research lab. Generally, proteins and short sequences of DNA do not enter our cells in large quantities with ease; in fact, the presence of foreign DNA in the bloodstream is actually a sign of infection and is rapidly combated using bodily enzymes. However, tiny snippets of DNA can be arranged densely on the surface of a nanoparticle – Dr. Samanta encourages her students to imagine a Koosh ball for reference (Figure 2) – and the resulting nanostructure is able to enter cells with a high degree of permeation, up to two orders of magnitude more than regular DNA.
This feature allows for the use of DNA nanostructures not only in gene therapy but also in the treatment of diseases and detection of genetic conditions, which is what the Samanta Lab focuses on.
Figure 2: A Koosh Ball
Following Dr. Samanta’s analogy, the tiny centre of the ball represents the chosen nanoparticle. The snippets of DNA that are attached to its surface are seen as spikes on the ball.
Learn More
If you’d like to hear more about the fascinating world of DNA and its immense potential, visit us on Spotify to listen to our ChemTalk podcast with Dr. Devleena Samanta, associate professor of chemistry at the University of Texas, Austin, to learn more about the favourite part of her job, why she wanted to be a scientist, and what she believes is the most important problem we need to solve.
Find the ChemTalk podcast here.
Works Cited
[1] “Deoxyribonucleic Acid Fact Sheet.” National Human Genome Research Institute. 24 August 2020.
[2] Rukkumani Rajagopalan, Jatinder V. Yakhmi, in Nanostructures for Cancer Therapy, 2017
[3] “What is DNA Origami?” BioSynthesis. 17 July 2017.
[4] Samanta, Devleena. Personal Interview. Conducted by Roxanne Salkeld. 2 December 2022.