New RNA-based “light switch” technology could speed disease testing

Researchers at the University of Florida have unveiled an affordable new technique that can spot single-letter genetic mutations in minutes, which could improve infectious disease testing, cancer genotyping and personalized medicine.

The new system, called FARSIGHT, acts like a programmable molecular “light switch.” When FARSIGHT encounters a perfectly matched genetic sequence, it folds into a fluorescent structure and lights up. Even a one-nucleotide mismatch, which is the smallest possible genetic letter difference, prevents activation.

In a study published in Nature Chemistry, researchers demonstrated that FARSIGHT can distinguish closely related viral variants, including SARS-CoV-2 lineages such as Omicron, with 100% accuracy in clinical saliva samples.

“With this work we can now not only recognize the existence of a specific virus but the strain of it as well, in a rapid, less expensive manner,” said Fan Hong, Ph.D., an assistant professor of chemistry at UF and co-author of the study. “Different strains of viral infections have to be treated differently, so this is critical in clinical settings.”

Unlike existing diagnostic tools such as PCR, FARSIGHT does not rely on enzymes, making it less expensive, simpler and more robust. The system uses engineered RNA switches paired with fluorescent molecules, enabling detection times as short as five minutes and a per test cost of under $2.

The switches remain dark unless they encounter an exact genetic match. This low background signal allows FARSIGHT to detect mutations present at just 0.1% of a sample, which is a level usually accessible only through specialized laboratory sequencing.

Because FARSIGHT switches are fully programmable, researchers can rapidly redesign them to target emerging pathogens, drug-resistant cancer mutations or even very small changes in RNA that are hard to detect. The system is compatible with portable testing equipment, making it ideal for point-of-care diagnostics and rapid outbreak response.

For now, the FARSIGHT system can only spot mutations in RNA, such as from RNA-based viruses, not DNA. But improvements are in the works. The team envisions using FARSIGHT to visualize mutations inside living cells allowing for the ability to transform cancer research and the study of DNA damage and repair.

“The next step is to use this expand the application of not just viral detection but genomic mutations, small molecule and protein markers as well,” Hong said.