New “miRacles” for Human Health

The path to studying microRNAs in diseases will be easier and cheaper, thanks to a new method developed by a team of researchers at the University at Albany.

The team, led by Ken Halvorsen and Bijan Dey, principal investigators in UAlbany’s RNA Institute, has created a DNA nanotechnology approach that enables label-free and unamplified detection of cellular microRNAs using gel electrophoresis.

MicroRNAs are short molecules of RNA (ribonucleic acid) that are involved in gene regulation. In diseases, certain microRNAs can have abnormal levels, which make them potentially useful molecules for therapeutics or diagnosis of various illnesses.

Detection of microRNAs, however, due to their small size and low levels, can be arduous and expensive, often requiring amplification, labeling or radioactive probes before they can be used for research and clinical purposes.

Halvorsen and Dey’s study, titled “Cellular microRNA detection with miRacles: microRNA activated conditional looping of engineered switches,” and published in the March 13 issue of Science Advances, has demonstrated detection without expensive equipment or reagents.

“We have used recent advances in DNA nanotechnology to create a switch made from DNA that can sense microRNAs and react by changing shape,” said Halvorsen. “Our approach is minimalistic, involving just a single mixing step, eliminating much of the cost and complexity typical to microRNA detection. We show how our method can detect various microRNAs from biological samples, and can be performed on the benchtop in as little as one hour.”

“We call it ‘miRacles,’” he added, “for ‘microRNA activated conditional looping of engineered switches,’ and it can be easily adopted by any lab.”

In the field of DNA nanotechnology, synthetic DNA is often used to build different shapes and structures. “Here, we use this concept to build a simple switch,” said Arun Richard Chandrasekaran, one of the lead authors on the study. “And we use the programmability of DNA to make this a plug-and-play device, so we can quickly custom make nanoswitches for any target.”

Dey commented, “This highly accessible technology, aiding biologists in the discovery and validation of microRNA biomarkers, has clinical potential as a simple, low cost way to detect biomarkers at the point-of-care. The miRacles technique then could be adapted for clinical use in detecting or monitoring diseases.”

The study was supported by grants from the National Institutes of Health through the National Institute of General Medical Sciences and the National Cancer Institute, and by the American Heart Association.

Other members of The RNA Institute research team that supported the study were Molly MacIsaac and Oksana Levchenko, undergraduate research assistants in Biological Sciences; Madeline Andres, an undergraduate research assistant from Cornell University; Lifeng Zhou, a UAlbany postdoctoral associate; and Paromita Dey, a senior research specialist.