Sarah Starcovic, a West Virginia University doctoral student in biochemistry and molecular medicine, conducts research in WVU School of Medicine Associate Professor Aaron Robart’s lab. Credit: WVU Photo/Hannah Maxwell
Researchers at West Virginia University have unveiled the intricate structure of DNAzymes by utilizing X-ray crystallography to capture an atomic-level view of its structure. The structural data obtained will prove to be essential for further optimization of DNAzymes and it’s potential future therapeutic applications.
Over the last few decades, researchers have been attempting to discover a method to encourage synthetic DNA to produce a reaction without the need for changing the DNA itself. In the study, published in Communications Chemistry, the researchers believe they have laid the groundwork to answer this longstanding question. “Atomic detail gives us a long-sought road map to start building and improving a technology that can be broadly applicable to health and diagnostics,” said Aaron Robart, associate professor in the WVU School of Medicine Department of Biochemistry and Molecular Medicine.
By utilizing X-ray crystallography, the researchers discovered that the structure of DNAzymes allowed them to find other sections of a complementary sequence and attach themselves together. “These DNAs can act as molecular scissors with precise specificity to cut RNA or DNA, or they can function as glue,” Robart explained. “Say you have a mutated gene that’s causing disease, we could get this DNA into the cells and it would be able to get rid of all that kind of message that’s causing the proteins that lead to the disease.”
The team intends to continue their research to capture DNAzymes at various points along their function to better understand how to optimize them. “It will be like we’re making an old school animation molecular flipbook,” Robart said. “This level of detail is used to understand how to improve, target and regulate their activity. This is only one of hundreds of different varieties of DNAzymes, all with their own unique properties begging to be applied to topics in human health.” They also have plans to collaborate with colleagues from the school of medicine to identify ways in which the model could be used for therapeutic applications.