Fewer than 1% of people who contract the flu are tested each year, in part because most tests need experienced professionals and expensive equipment. Researchers have developed a low-cost paper strip test that could help more patients identify the type of flu they have and receive the appropriate medication.
The test, developed by a team from the Broad Institute of MIT, Harvard, and Princeton University, and funded by the US Centers for Disease Control and Prevention, employs CRISPR to distinguish between the two main types of seasonal flu, influenza A and B, as well as seasonal flu subtypes H1N1 and H3N2. It can also identify strains that resist antiviral treatment, and with further work, could potentially detect swine and avian flu strains, including H5N1, which is currently infecting cattle.
Appearing in The Journal of Molecular Diagnostics, the results could help improve outbreak response and clinical care by bringing tests that are accurate, low-cost, and fast to doctors’ offices and labs across the US and in other countries.
Using paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes.
Ben Zhang
“Ultimately, we hope these tests will be as simple as rapid antigen tests, and they’ll still have the specificity and performance of a nucleic acid test that would normally be done in a laboratory setting,” said Cameron Myhrvold, co-senior author on the study along with Pardis Sabeti, an institute member at the Broad and a professor at Harvard University and the Harvard T.H. Chan School of Public Health, as well as a Howard Hughes Medical Institute investigator. Myhrvold, who is currently an assistant professor at Princeton University, was a postdoctoral researcher in Sabeti’s lab when the study began.
SHINE a light
The test is based on a method called SHINE, which was created by Sabeti’s lab in 2020 and employs CRISPR enzymes to detect specific viral RNA sequences in samples. The researchers first utilized SHINE to detect SARS-CoV-2, then to differentiate between the Delta and Omicron strains. Then, in 2022, they started customizing the assay to detect additional viruses that they knew were constantly present: influenzas. They intended to develop tests that could be utilized in the field or in clinics rather than hospitals or diagnostic labs with high-end equipment.
“Using a paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” said Ben Zhang, co-first author on the study, a medical student at Harvard Medical School and an undergraduate researcher in Sabeti’s lab when the study began.
Typical diagnostic approaches such as polymerase chain reaction (PCR) require lengthy processing times, trained personnel, specialized equipment, and freezers to store reagents at -80°C, whereas SHINE can be conducted at room temperature in about 90 minutes. Currently, the assay only requires an inexpensive heat block to warm the reaction, and the researchers are working to streamline the process with the goal of returning results in 15 minutes.
The researchers also adapted SHINE to distinguish between different flu strains. In the future, they say the assay could be adapted to detect two different viruses with similar symptoms, such as influenza and SARS-CoV-2.
“Being able to tease apart what strain or subtype of influenza is infecting a patient has repercussions both for treating them and public health interventions,” said Jon Arizti-Sanz, a postdoctoral researcher in Sabeti’s lab and co-first author on the study.
For example, the testing could assist clinicians in deciding whether to take Oseltamivir, a common antiviral that is only effective against a subset of strains, Arizti-Sanz said. Rapid testing could also help scientists collect samples more strategically during an outbreak, allowing them to better monitor how the virus spreads.
Next, the researchers are modifying SHINE to detect both avian and swine influenza strains. “With SARS-CoV-2 and now flu, we’ve shown that we can easily adapt SHINE to detect new or evolving viruses,” Arizti-Sanz told reporters. “We’re excited to apply it to H5N1.”
