Shape switching RNA nanoparticles
The scientists used various methods to characterize RNA nanoparticles with different shapes and compositions, shown here. The model included cubes composed of RNA only, DNA only, and various combinations of RNA and DNA strands.   
The figure is reproduced under the terms of the copyright agreement from Halman JR et al. Functionally-interdependent shape-switching nanoparticles with controllable properties. Nucleic Acids Res. 2017 Feb 28;45(4):2210-2220.

Scientists have discovered an efficient and straightforward model to manipulate RNA nanoparticles, a new concept that could help trigger desirable activation of the immune system with vaccines and therapies.

A multi-institutional team of researchers used an approach to fine tune DNA and RNA nanoparticles to activate multiple biological functions and pathways. The group recently published its findings in Nucleic Acids Research.

For the study, scientists from the Frederick National Lab, University of North Carolina at Charlotte (UNCC), National Cancer Institute, Pavol Jozef Safarik University in Slovakia, and Ball State University focused on RNA nanoparticles since they are more reactive and can activate stronger immune responses than their DNA counterparts. RNAs not only carry genetic information but have additional functions through regulation of gene expression and editing. 

Building on previous studies, the researchers used advanced technology and computer simulations to characterize RNA nanoparticles with different shapes and compositions. The model included cubes composed of RNA only, DNA only, and various combinations of RNA and DNA strands. 

Kirill Afonin, Ph.D., assistant professor of chemistry, UNCC, who is the project’s principal investigator, developed a unique technology that allows for assembling traditional DNA and RNA oligonucleotides—short molecules that have a wide range of applications in research—into nanostructures of different shapes that nature doesn’t produce.

Portrait photo“We know how the immune system handles host DNA and RNA and how it responds to therapeutic nucleic acids such as RNAi or antisense oligonucleotides,” explained Marina Dobrovolskaia, Ph.D., MBA, senior principal scientist, head of the Nanotechnology Characterization Laboratory’s Immunology Section, and co-author of the study. “However, it is unknown how the immune system reacts to DNA/RNA nanoparticles which are made of the traditional nucleic acids assembled into nanostructures with different shapes. We are filling this gap by determining the immune recognition of these novel materials.”

The research team studied structural activity relationships using engineered DNA/RNA nanomaterials, which allowed the scientists to determine which structures were responsible for producing desirable or undesirable effects, Dobrovolskaia said.

The group worked with two nucleic acid structures that are invisible to the immune system and separately have no functions. Using various methods such as computational predictions, 3D modeling, nanoparticle assembly and purification, imaging, and statistical analysis, the research team reassembled the nanoparticles to form structures possessing important biological functions that can stimulate the immune system.

The scientists’ work is addressing a critical need in nanoscience. Not only does the research advance understanding of the field, but it also serves a safety and environmental health need by informing agencies like the FDA and EPA about the potential dangers of working with RNA nanoparticles.    

“The resources we have here at the Nanotechnology Characterization Laboratory are unique,” said Dobrovolskaia. “We are combining these resources to deliver results to the research community, but we are also informing regulators about what is safe and what is not safe with this type of science.”  

Further collaborative research between UNCC and the Nanotechnology Characterization Laboratory is underway to determine a precise mechanism for immune recognition of these particles, which could have a significant impact on the promising future of using nanoparticles to trigger desirable health effects and avoid undesirable toxicities.

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