A New Era in Gene Therapy and DNA Nanotechnology with Triplex Origami

by Henrik Andersen
5 comments
Triplex Origami

Scientists have devised a novel technique known as triplex origami, which utilizes Hoogsteen interactions to create diverse compact DNA structures. This groundbreaking approach has the potential to significantly impact gene therapy and DNA nanotechnology, as it safeguards DNA from enzymatic degradation. However, its dependency on certain building blocks is a challenge currently being addressed.

Researchers at Aarhus University’s Gothelf lab have crafted an innovative technique, triplex origami, to control DNA shaping and denseness. This development promises intriguing opportunities in various fields like gene therapy, nanotechnology, and beyond.

Inside each of your cells, there’s about 2 meters of DNA that contains the critical genetic information that defines you. If we unraveled all the DNA in a single human, it would cover an awe-inspiring distance, capable of going to the sun and back over 60 times. To manage these extraordinarily long molecules, the cell condenses its DNA into compact parcels, known as chromosomes.

“Our genetic information is inscribed on DNA, liken it to a sheet of paper,” comments Minke A.D. Nijenhuis, co-lead author of the new study. “This ‘sheet’ is folded into a highly compact structure to fit the small cell nucleus. However, to access this information, portions of the ‘paper’ must be unfolded and then refolded. We aimed to develop a technique that lets scientists engineer and examine the condensation of double-stranded DNA.”

![Image](Researchers from Aarhus University have discovered a new method for constructing and studying the packaging of DNA. Credit: Colourbox)

The Triple Helical Structure: A Beacon of Protection and Compactness

Typically, DNA is composed of two strands twisted together forming a double helix. One strand encodes our traits, while the other serves as a backup. These strands are bound together by Watson-Crick interactions. There’s another less recognized type of interaction, known as normal or reverse Hoogsteen interactions, allowing a third strand to form a triple helix, a triplex.

![Image](New research shows that by using a new method called triplex origami one can create triple DNA helices that can bend or “fold” DNA into compact structures. Credit: Minke A. D. Nijenhuis)

In a recent paper published in the scientific journal Advanced Materials, Gothelf’s lab introduced a simple method for organizing DNA strands based on Hoogsteen interactions. This technique enables DNA to fold into diverse compact structures, ranging from hollow two-dimensional shapes to dense three-dimensional constructions. The technique is known as triplex origami.

Unleashing the Potential in Gene Therapy and More

Triplex origami enables unprecedented control over DNA shape, paving the way for innovative research opportunities. Previous studies indicated that triplex formation plays a part in natural DNA packaging within cells, and this study could further our understanding of this critical biological process.

Moreover, triplex formation shields DNA from enzymatic degradation. This feature of the triplex origami technique could prove vital in gene therapy, where faulty cells are rectified by introducing a missing function via a DNA package.

![Image](Triplex-mediated folding of dsDNA, a) A dsDNA sequence containing triplex-forming domains (coloured) is folded by four TFO strands, i.e. single-stranded DNA acting as staples, into a hairpin structure b) Images of two hairpin structures made with atomic force microscopy (AFM). c) S-shaped structure formed from a polypyrin DNA. d) Assembly of a large TFO origami resembling a potted flower structure from a 9000 bases long piece of double-stranded DNA. Scale bar = 100 nm. Credit: Gothelf Lab, Aarhus University)

The remarkable properties of DNA’s sequence and structure have already been harnessed in nanotechnology, influencing medical treatments, diagnostics, and more. “DNA nanotechnology has traditionally depended almost entirely on Watson-Crick base interactions to assemble single-stranded DNA into customized nanostructures for the past forty years,” says Professor Kurt V. Gothelf. “We now understand that Hoogsteen interactions offer the same potential for organizing double-stranded DNA, marking a substantial conceptual expansion in this field.”

Gothelf’s team has shown that Hoogsteen-mediated folding is compatible with conventional Watson-Crick-based methods. With the relative rigidity of double-stranded DNA, triplex origami structures demand fewer starting materials, making larger structures cost-effective.

However, the technique has a drawback that it typically requires long stretches of a specific building block, known as purine bases, which led researchers to use artificial DNA sequences instead of natural genetic DNA. They plan to overcome this limitation in future works.

Source: “Folding Double-Stranded DNA into Designed Shapes with Triplex-Forming Oligonucleotides” by Cindy Ng, Anirban Samanta, Ole Aalund Mandrup, Emily Tsang, Sarah Youssef, Lasse Hyldgaard Klausen, Mingdong Dong, Minke A. D. Nijenhuis and Kurt V. Gothelf, 13 June 2023, Advanced Materials.
DOI: 10.1002/adma.202302497

Frequently Asked Questions (FAQs) about Triplex Origami

What is Triplex Origami?

Triplex Origami is a novel technique developed by scientists that uses Hoogsteen interactions to fold DNA into various compact shapes. It shows potential benefits for gene therapy and DNA nanotechnology by protecting DNA from enzymatic degradation.

Who developed the Triplex Origami method?

The Triplex Origami method was developed by researchers at the Gothelf Lab at Aarhus University.

How does the Triplex Origami method work?

The Triplex Origami method works by utilizing a less recognized type of interaction between DNA strands, known as normal or reverse Hoogsteen interactions. These interactions allow a third DNA strand to join and form a triple helical structure, a triplex. The DNA can then be bent or folded in a way that creates compact structures.

Why is the Triplex Origami method important for gene therapy?

Triplex origami enables unprecedented control over the shape of DNA molecules, opening up new possibilities for research. It also shows that triplex formation protects DNA from enzymatic degradation. This feature could be very important in gene therapy, where diseased cells are repaired by delivering a function they lack via a DNA package.

What are the limitations of the Triplex Origami method?

The current limitation of the Triplex Origami method is its requirement for long stretches of a specific building block, called purine bases. In the initial research, the scientists used artificial DNA sequences instead of natural genetic DNA, but they plan to overcome this limitation in future works.

More about Triplex Origami

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5 comments

BioGeek42 June 18, 2023 - 4:58 pm

Imagine the applications of this in gene therapy! This could be a real game-changer… And props to the team at Aarhus Uni, great job.

Reply
NeilBio101 June 19, 2023 - 4:11 am

This Triplex Origami sounds fascinating, but I’m curious how they’re planning to overcome the limitation of needing purine bases? Hope they update us on progress soon.

Reply
SarahScienceFan June 19, 2023 - 4:14 am

Amazing! dna folding in compact shapes, the implications for gene therapy could be revolutionary. Can’t wait to see where this leads.

Reply
TechGuru123 June 19, 2023 - 8:02 am

Reading this I was like, DNA what now? But I get it, they’re using dna as a building block, similar to nano tech. Crazy stuff, thanks for sharing!

Reply
JohnD87 June 19, 2023 - 10:26 am

Wow, this is some serious sci-fi stuff! Who’d’ve thought we could fold DNA like origami… the future’s here, folks!

Reply

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