Outsmarting COVID-19 and other viruses by analyzing RNA in single cells

Despite the rapid development of vaccines and drugs against COVID-19, the pandemic has left scientists with many vexing questions. What makes some people super-spreaders of SARS-CoV-2, the virus at the heart of the pandemic? Is the virus evolving so it can escape vaccines or treatments? The ability to answer those questions could point the way toward new therapeutic targets.

Scientists at Rutgers University have developed a way to detect changes in RNA at the single-cell level. Their tool, dubbed surface-enhanced Raman spectroscopy (SERS), signals that molecules are interacting by detecting subtle changes in how they give off light. They described the technique at the virtual meeting of the American Chemical Society.

“For studying a new virus like SARS-CoV-2, it’s important to understand not only how populations respond to the virus, but how individuals—either people or cells—interact with it,” said principal investigator and Rutgers associate professor Laura Fabris, Ph.D., in a statement. The technique developed in Fabris’ lab could overcome hurdles that in the past prevented efforts to study viral replication in single cells, she added.

To start, the Rutgers team used SERS to scrutinize the influenza A virus. They took DNA that’s specific to the virus and attached it to gold nanoparticles. SERS gave off a strong signal in the presence of flu RNA. But as the virus mutated, the signals got weaker. The team was able to detect changes in RNA that were so tiny they covered just two nucleotides, they reported.

RELATED: Qiagen launches new tools for tracking coronavirus mutations and strains

The ability to answer questions about how SARS-CoV-2 is evolving over time is a priority among researchers developing treatments and vaccines. Earlier this week, Qiagen introduced new tools that use reverse transcription to map the coronavirus’s evolution over time. They published research showing how the technology was able to detect changes in the SARS-CoV-2 genome, which included variations in the spike protein that allows it to infect healthy cells.

Fabris and her Rutgers colleagues are seeking funding for further research aimed at identifying areas of the SARS-CoV-2 genome that can be targeted with SERS. They are also working on a version of their assay that uses fluorescent signals in place of SERS, though Fabris believes SERS could prove to be more sensitive and less expensive. So, she has teamed up with a company to develop a portable SERS testing device.