Some years, as much as 20% of the U.S. population becomes infected with the influenza virus, according to the Centers for Disease Control. Most people who get the flu experience mild illness that amounts to little more than an unpleasant inconvenience. However, some cases of the flu can be very severe, and even mild cases can be life-threatening for young children, the elderly, and those with certain medical conditions. For these vulnerable patients, early treatment with antiviral drugs is critical.
Yet, to be treated, the flu must first be diagnosed, and doing that is not as easy as many clinicians would like. Although there are two different kinds of tests that can be used to diagnose the flu while a patient is in the doctor’s office, these tests don’t catch every case. A third test is more accurate, but requires processing and analysis in a lab, making it more expensive and time-consuming as well. The net effect is that critical treatment may be delayed, if it happens at all.
Xiao-Wen Cheng is working on a better way. An associate professor of microbiology at Miami University, Cheng’s innovation is to detect a virus directly, using a method that doesn’t require extracting viral RNA. Detecting a virus directly is more diagnostically reliable than detecting the antibodies a patient has developed in response to a viral infection – the method used in currently available rapid influenza diagnostic tests (RIDTs) – because patients in the very early stages of infection may not yet have developed antibodies. Cheng’s method is also cheaper and faster than direct-detection lab tests that rely on RNA extraction.
The key to Cheng’s innovation is an engineered enzyme known as RTAKAS-mix. RTAKAS-mix was initially inspired by an enzyme produced by a group of German scientists. That enzyme – which Cheng learned about in a paper the team published – was capable of detecting certain viruses. However, as Cheng discovered when he replicated it, the enzyme was not very robust, so its usefulness in practical applications was limited.
To benefit clinicians and patients, Cheng knew a useful viral diagnostic enzyme would have to be sturdy enough to withstand some harsh conditions. “Diagnostic test kits have to be shipped from the manufacturer to doctors’ offices,” he says. “They’re transported by truck across the country all year. It can be more than 100 degrees Fahrenheit inside a truck in the summer, and the test kit has to be able to survive that.”
Since the enzyme originally created by the German team was not that robust, Cheng and his team put the enzyme through a series of mutations, finally developing the stable, long-lived RTAKAS-mix, which can withstand temperatures up to 54°C (129°F) for at least two days.
Once his lab had an optimized enzyme, Cheng needed a path to commercialization, so he applied and was accepted to I-Corps@Ohio, a program that uses methodologies pioneered by the National Science Foundation in its Innovation Corps (I-Corps) program. As its website explains, I-Corps@Ohio is “a statewide grant-funded program to assist faculty and graduate students from Ohio universities and colleges to validate the market potential of their technologies and launch startup companies.”
In addition to Cheng, who serves as the project’s principal investigator, the I-Corps@Ohio project team includes Michael Nau, a senior microbiology major and management minor who serves as the entrepreneurial lead; Hui Shang, a graduate student in the cell, molecular, and structural biology program who serves as the co-entrepreneurial lead; and Dan Rose, an angel investor, entrepreneur, and I-Corps@Ohio instructor who serves as the entrepreneurial mentor.
Together, Nau and Shang interviewed more than 100 potential customers – nurses, doctors, veterinarians, and other clinicians – to learn about their day-to-day practices and what they need from a viral diagnostic tool. Some of the interviews were via phone or email, but many of them were in person, with Cheng driving Nau and Shang to hospitals and doctors’ offices all over the Columbus area.
One insight that came from the interviews surprised Cheng: when it comes to flu, clinicians don’t really care about viral load, or how many copies of the virus are circulating in a patient’s body. Cheng’s test is so sensitive it can detect the presence of a single virus particle in a sample, and that’s all that’s needed for the flu – a simple infected/not infected diagnosis is enough to make appropriate treatment decisions.
But Cheng’s test can also determine viral load, and he learned from the interviews with clinicians that viral load is very important to treatment decisions for certain other viral infections, including HIV. Cheng has already used RTAKAS-mix to detect FIV, a feline virus similar to HIV that causes an AIDS-like disease in cats. Now he’s heading back to the lab to see if he can apply his solution to develop a direct-detection test for HIV – and HIV viral load – that doctors can use in their offices while patients wait.
At the same time, Cheng and his I-Corps@Ohio team will look for an investor to form a company that will manufacture and market a flu test kit using RTAKAS-mix. “The company will probably operate for a short time before it is bought by a larger company,” he says. “That’s the business model, to attract investment through acquisition.”
Being involved, however briefly, in the management of the new start-up company will provide Nau and Shang with valuable experience. Even negotiating their eventual exit from the company will become part of a roadmap they can use to navigate future entrepreneurial ventures.
That’s important because commercialization of biomedical innovations is as critical to improving the lives of Ohio’s citizens and ensuring the vibrancy of its economy as the scientific discoveries behind those innovations. After all, as Cheng puts it, “If technology stays in the lab, it creates no value.”
Written by Heather Beattey Johnston, Associate Director of Research Communications, Office for the Advancement of Research and Scholarship, Miami University.
Photo of Xiao-Wen Cheng by Jeff Sabo, Miami University Photo Services. Photo of I-Corps@Ohio project team by I-Corps@Ohio.