Scientists at Aarhus University have actually established an approach called triplex origami, using Hoogsteen interactions to fold DNA into different compact shapes, offering prospective advantages for gene therapy and DNA nanotechnology. The approach safeguards DNA from enzymatic degradation and could transform the method we manipulate DNA, though existing limitations in requiring specific foundation are being dealt with.
Researchers from the Gothelf lab at Aarhus University have developed an innovative new approach, called triplex origami, to manipulate the shape and tight packing of DNA. The discoveries open interesting brand-new possibilities in gene treatment, nanotechnology, and more.
Every cell in your body contains about 2 meters of DNA, which carries the important genetic info about you as an individual. It would extend over a shocking distance– enough to reach the sun and back once again over 60 times if you unwind all the DNA included in a single individual. To deal with such astonishingly long particles, the cell compresses its DNA into compact packages called chromosomes.
Says Minke A.D. Nijenhuis, co-corresponding author of the brand-new paper. “The paper is folded in an extremely tight structure to fit all this information in a small cell nucleus. We, for that reason, desired to produce a method that allows researchers to engineer and study the compaction of double-stranded DNA.”
In the brand-new post released in the clinical journal Advanced Materials, scientists from Gothelfs laboratory at Aarhus University have actually introduced a simple approach for arranging DNA strands. The research reveals that utilizing this technique, DNA can be bent or “folded” in a method that creates compact structures. Figure 3: Triplex-mediated folding of dsDNA, a) A dsDNA series including triplex-forming domains (coloured) is folded by 4 TFO strands, i.e. single-stranded DNA performing as staples, into a hairpin structure b) Images of two hairpin structures made with atomic force microscopy (AFM). Due to the relative rigidness of double-stranded DNA, nevertheless, triplex origami structures require fewer beginning products. Here the scientists have used artificial DNA sequences rather of natural hereditary DNA.
Figure 1: Researchers from Aarhus University have actually found a brand-new method for building and studying the packaging of DNA. Credit: Colourbox
Triple helical structure provides protection and compactness
In nature, DNA is typically made up of two strands that are twisted together into a double helix. In addition to these widely known interactions, there is a lesser-known type of interaction between DNA strands.
Figure 2: New research reveals that by utilizing a new technique called triplex origami one can create triple DNA helices that can bend or “fold” DNA in into compact structures. Credit: Minke A. D. Nijenhuis
In the new post released in the scientific journal Advanced Materials, researchers from Gothelfs laboratory at Aarhus University have actually presented a basic approach for arranging DNA strands. The method is based upon the previously mentioned Hoogsteen interactions. The research study reveals that using this method, DNA can be bent or “folded” in such a way that creates compact structures. These structures can take different kinds, from hollow two-dimensional shapes to thick three-dimensional building and constructions and whatever in between. In reality, you can even produce structures that look like a potted flower. The scientists call their technique triplex origami (figure 3).
Potential in gene therapy and beyond
Using triplex origami, researchers can attain unmatched control over the shape of DNA particles, opening up brand-new possibilities for research study. Previous research studies have actually recommended that triplex formation contributes in the natural product packaging of DNA in cells, and this research study can help us discover more about this critical biological process.
The research study likewise shows that triplex development safeguards DNA from enzymatic degradation. The capability to secure and compress DNA utilizing the triplex origami method might therefore be of great value in gene treatment, where diseased cells are repaired by providing a function they do not have via a DNA bundle.
Figure 3: Triplex-mediated folding of dsDNA, a) A dsDNA series including triplex-forming domains (coloured) is folded by four TFO hairs, i.e. single-stranded DNA acting as staples, into a hairpin structure b) Images of 2 hairpin structures made with atomic force microscopy (AFM). c) S-shaped structure formed from a polypyrin DNA. d) Assembly of a big 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 biological properties of DNAs series and structure have already been made use of in nanotechnology, which has actually had an impact on medical treatments, diagnostics, and lots of other locations. We now understand that Hoogsteen interactions have the very same potential to arrange double-stranded DNA, which provides a significant conceptual growth for the field.”
Gothelf and co-workers showed that Hoogsteen-mediated folding works with modern Watson-Crick-based approaches. Due to the relative rigidness of double-stranded DNA, nevertheless, triplex origami structures require less starting materials. This allows bigger structures to be formed at a substantially lower expense.
The brand-new method has the restriction that triplex development normally requires long stretches of a particular structure block, called purine bases. Here the scientists have used synthetic DNA sequences rather of natural hereditary DNA. In the future, they will work towards overcoming this limitation.
Referral: “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.