The researchers improved the stability of the DNA nanostructures

June 06, 2023

(Nanowerk News) Researchers at the University at Albany’s RNA Institute have demonstrated a new approach for assembling DNA nanostructures that does not require magnesium. This method improves the biostability of the structure, making it more useful and reliable in a variety of applications. The work appears in the journal Small (“Self-assembly of DNA Nano Structures in Various Cations”).

When we think of DNA, the first association that comes to mind is most likely genetics – the double helix structure inside cells that houses an organism’s blueprint for growth and reproduction. A rapidly growing area of ​​DNA research is that of nanotechnology and DNA nanostructures — synthetic molecules composed of the same building blocks as DNA found in living cells, engineered to solve critical challenges in applications ranging from medical diagnostics and drug delivery to materials science and data storage.

“In this work, we assembled DNA nanostructures without the use of magnesium, which is normally used in this process, but came with challenges that ultimately reduce the usefulness of the resulting nanostructures,” said Arun Richard Chandrasekaran, the study’s corresponding author and senior investigator. scientist at the RNA Institute. “For example, magnesium can cause DNA nanoparticles to agglomerate, which changes the characteristics of the drug being delivered. This can interfere with drug loading in the body, which in turn reduces drug efficacy. Magnesium can also increase the activity of enzymes in the body that degrade DNA, thereby reducing the lifespan of nanostructures in the body.”

The research team, including scientists at the University of Illinois Urbana-Champaign, collected four types of DNA nanostructures in six different metal ions including calcium, barium, sodium, potassium and lithium, as well as magnesium. Images of four types of DNA nanostructures assembled by the team using six different metal ions including calcium, barium, sodium, potassium, lithium and magnesium. (Image: University at Albany and University of Illinois at Urbana-Champaign)

“We found that DNA nanostructures assembled in monovalent ions (sodium, potassium, lithium) are much more biostable than those assembled in divalent ions (magnesium and calcium),” said Chandrasekaran. “We demonstrated the broad applicability of our findings by assembling four types of DNA nanostructures of different complexity and size using these different ions. These range from small DNA motifs such as the double crossover motif and the three-pointed star motif to larger assemblies such as the DNA tetrahedron and the DNA origami triangle.

“Assembling structures that can withstand degradation by nucleases, such as the one we have assembled here, will be useful in biological applications such as drug delivery where the DNA nanostructures used as drug carriers must be intact until delivering the drug to the target. site.”

“Our work focuses on identifying conditions that can be used to build an effective drug delivery system,” said Arlin Rodriguez, the study’s first author and research support specialist in the Chandrasekaran lab at the RNA Institute. “One of the important aspects highlighted in this study is the resistance of nanostructures assembled in monovalent ions to nuclease degradation, which is useful for preventing damage to these structures in the presence of nucleases. The increased durability of these nanostructures can help optimize drug release in the body.”

“Magnesium has traditionally been the main ion used in the assembly of DNA nanostructures,” said first co-author Dhanush Gandavadi, a PhD student at the University of Illinois Urbana-Champaign. “However, by limiting ourselves to magnesium, we have neglected the possibility of assembling DNA nanostructures using alternative ions.” “Our study broadens the design horizons of DNA nanostructures and facilitates the development of superior drug delivery systems by exploring diverse ions,” said co-author Xing Wang, a member of the biotechnology and chemistry faculty at the University of Illinois Urbana-Champaign.

“In addition, our study sheds light on the influence of various ions on the stability and compactness of DNA origami nanostructures, thereby broadening our understanding of their basic properties.”

Next, the team plans to further optimize the assembly of the nanostructures in various metal ions for higher assembly yields, and to test the biostability of the assembled structures in the absence of magnesium in the cells.

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