Less than one percent of individuals who contract the flu each year undergo testing, mainly due to the need for trained professionals and costly equipment for most tests. However, researchers have now created an affordable paper strip test that could enable more patients to determine which strain of flu they have and receive appropriate treatment.
The test, developed by a team from the Broad Institute of MIT and Harvard, as well as Princeton University and supported by the US Centers for Disease Control and Prevention, utilizes CRISPR technology to differentiate between the primary seasonal flu types, influenza A and B, along with seasonal flu subtypes H1N1 and H3N2. It can also pinpoint strains that are resistant to antiviral treatment and has the potential to detect swine and avian flu strains like H5N1, presently affecting cattle.
The findings published in The Journal of Molecular Diagnostics could enhance response to outbreaks and healthcare by making accurate, low-cost, and rapid tests available in doctors’ offices and labs nationwide and abroad.
“Ultimately, we aim for these tests to be as easy to use as rapid antigen tests while maintaining the specificity and performance of a nucleic acid test typically performed in a laboratory environment,” explained Cameron Myhrvold, co-senior author of the study alongside 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, currently an assistant professor at Princeton University, was a postdoctoral researcher in Sabeti’s lab at the start of the study.
SHINE a light
The test is based on a technology known as SHINE, developed by Sabeti’s lab in 2020, which employs CRISPR enzymes to identify specific viral RNA sequences in samples. Initially, SHINE was used to test for SARS-CoV-2 and later to differentiate between the Delta and Omicron variants. In 2022, the researchers began adapting the assay to detect other viruses that are consistently circulating, such as influenza. Their aim was to create tests suitable for use in the field or in clinics without requiring expensive equipment found in hospitals or diagnostic labs.
“The use of a paper strip readout instead of costly fluorescence machinery represents a significant advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” stated Ben Zhang, co-first author of the study, a medical student at Harvard Medical School, and an undergraduate researcher in Sabeti’s lab during the study’s inception.
Traditional diagnostic methods like polymerase chain reaction (PCR) involve lengthy processing, trained personnel, specialized equipment, and storage at -80°C, while SHINE can be performed at room temperature in about 90 minutes. Currently, the assay only necessitates an inexpensive heat block for reaction warming, and efforts are underway to expedite the process with the goal of delivering results within 15 minutes.
The researchers also adapted SHINE to differentiate between various flu strains. In the future, they suggest that the assay could be modified to detect two different viruses with similar symptoms, such as influenza and SARS-CoV-2.
“Distinguishing the strain or subtype of influenza infecting a patient has implications for both treatment and public health strategies,” noted Jon Arizti-Sanz, a postdoctoral researcher in Sabeti’s lab and co-first author of the study.
For instance, the tests could aid clinicians in deciding whether to administer Oseltamivir, a common antiviral effective against only certain strains, added Arizti-Sanz. In the field, rapid testing could assist researchers in strategically collecting samples during an outbreak to monitor the virus’s spread more effectively.
Next, the researchers are adapting SHINE to detect both avian and swine influenza strains. Arizti-Sanz remarked, “With SARS-CoV-2 and now the flu, we have demonstrated the adaptability of SHINE to detect new or evolving viruses. We are eager to apply it to H5N1.”
