West Virginia University researchers are now able to look at synthetic DNA at the atomic level, giving them the ability to understand how to change its structure in hopes of improving its scissor-like function. Learning more about these synthetic DNA reactions could be the key to unlocking new technology for medical diagnosis and treatment.
In the world of chemistry, the findings help answer a 30-year-old question about this specific DNA structure and how scientists can get it to perform a reaction without changing the DNA itself, a process called catalysis.
The researchers’ findings were published in Chemistry of Communication.
“This is only, perhaps, the third example that lends views, at the very detailed atomic level, of how chemically active DNA promotes their unique functions that give all these applications their power,” said Aaron Robart, associate professor in the WVU School of Medicine Department of Biochemistry and Molecular Medicine, and principal investigator of the project. “Atomic detail gives us a long-sought road map to begin building and improving a technology that can be used widely in health and diagnostics.”
Robart said that if scientists understand how to make the technology more efficient, it could theoretically be used as a treatment for diseases such as retinal degeneration or cancer.
Robart pointed out that the synthetic DNA used in the study, known as DNAzymes, is different from human DNA. Created in a lab, DNAzymes are inexpensive to produce and can catalyze chemical reactions. It is artificially created to perform functions such as monitoring air quality and measuring heavy metals dissolved in the soil.
“Typically, we think of DNA as inert, serving as a storage unit for our genetic information,” says Robart. “However, there are some types of DNA that have evolved in the laboratory that defy the usual rules. These DNAs can be folded into complex shapes, which enable them to perform an amazing variety of reactions.
“The only problem is, after 30 years of research, we don’t really know how any of the chemistry is happening. One of the big things we’re missing is what our lab is doing with crystals, resulting in high-resolution structures of what nucleic acids look like down to atomic detail and how they do all this chemistry.”
To see DNA at the atomic level, Robart and his lab students, Evan Cramer, in Lake Ann, Michigan; Sarah Starcovic, of Cameron; and Beka Avey of Martinsburg, working with the Advanced Photon Source at the US Department of Energy’s Argonne National Laboratory in Chicago. The process—X-ray crystallography—involves crystallizing synthetic DNA and then zapping it with super powered X-rays to reveal its structure. Working with APS, the team was able to control X-rays and collect data via the internet.
“Using this information, we can better understand what other DNAzymes can do in their cleavage reactions,” said Starcovic, who is pursuing a doctoral degree in biochemistry and molecular medicine.
Robart said that what they see is a structure with small arms that can reach to find another section in a complementary sequence and clamp themselves, similar to the way Velcro is attached.
“These DNAs can act as molecular scissors with the right specificity to cut RNA or DNA, or they can act as glue,” explains Robart. “Say you have a mutated gene that causes a disease, we can make this DNA in the cells and it can get all kinds of messages that cause proteins that lead to the disease.”
Cramer, lead author of the published paper and a biochemistry and molecular medicine student, hopes that future studies will fill the knowledge gaps for clinical implementation.
“It’s hard to improve something when you don’t fully know how it works,” he said.
Robart says the next step is to focus on alternative methods to capture DNAzymes at different points in their function.
“It’s like we’re doing an old school molecular flipbook animation,” Robart said. “This level of detail is used to understand how to develop, target and regulate their activity. This is just one of hundreds of different types of DNAzymes, all with their own unique properties that beg to be used in human health topics.”
He said he also hopes to gain insight from colleagues at the School of Medicine on how model systems can be used for therapeutics.
“We’re in a unique place,” Robart said. “We have a potential cure for a disease. I feel fortunate to be in an environment surrounded by so many talented collaborators at the School of Medicine to help this exciting technology reach its full potential.”
More information:
Evan R. Cramer et al, Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation, Chemistry of Communication (2023). DOI: 10.1038/s42004-023-00924-3
Provided by West Virginia University
Citation: Researchers capture atomic view of synthetic DNA, revealing ‘molecular scissors’ that could cure disease (2023, July 24) retrieved on July 24, 2023 from https://phys.org/news/2023-07-capture-atomic-view-synthetic-dna.html
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