This article originally appeared on the UKRI Biotechnology and Biological Sciences Research Council website.
Jake Carter, a PhD student at BHP founder-member the University of Birmingham, was in his last year when COVID-19 and the first England lockdown forced him to leave the lab and stay at home.
With the support of his supervisors, university colleagues, the business that hosted his placement and the wider research community, he was able to translate his work in assays into a new test for the virus.
The test takes less than 5 minutes using a technique they have called Reverse Transcriptase Free EXPAR (RTF-EXPAR) and is now being tested by the NHS. The preprint paper describing the process on MedRxiv lists Jake Carter as lead author. Jake and the team are currently exploring how to make the test easier to deploy and use as part of opening up society, plus exploring its potential use for other diseases.
Labs locked down
Jake Carter’s research had gone well, papers were in and he could have concentrated on the write-up. But as his co-supervisor, Professor Tim Dafforn from the School of Biosciences, explains, “he said he wanted to make a difference and create a COVID-19 assay. He went into the lab and, though we provided the intellectual support, he has been incredible.”
Jake’s two co-supervisors, Tim and Professor Jim Tucker from the School of Chemistry, were frustrated by the lack of activity to mobilise the academic sector; with nowhere to create and shape ideas like Jake’s to tackle the national public health emergency.
The two co-supervisors bring a wealth of experience to the BBSRC Midlands Integrative Bioscience Training Partnership. Along with several BBSRC and UKRI grants for their research, Tim has received a BBSRC Enterprise Fellowship to spin out Linear Diagnostics and held positions in the Department for Business, Enterprise, Innovation and Skills (BEIS). This experience and their connections meant they were well placed to organise a series of town hall style meetings for academics, including Jake, to address the pandemic.
Tim outlines how it happened: “I knew we had the intellectual capacity in the UK to do something, and we needed to find a way to self-organise, so we did it ourselves. We thought we could do something, so we set up a group in the Midlands. It was like a community group. By the time we were finished, we were having meetings with 40 or so scientists from all sorts of different areas, just brainstorming ideas and trying to link up.”
He was keen the meetings be as inclusive as possible: “When we had those first meetings, we didn’t consider whether people would be useful; we just considered people who might be of the right mind to have some exciting ideas. And Zoom is a great enabler of these things; it’s almost better than doing it face to face because you remove some of the hierarchical issues – Jake is a window like I am a window.”
Those meetings strengthened the Birmingham team’s resolve to develop a new and faster assay. As part of Jake’s Doctoral Training Programme, he had completed a work placement with Linear Diagnostics Ltd (a University of Birmingham spin-out) to better understand the practical aspects of assay research and to increase his bioscience skills. The relationships and skills he had developed with the team there now meant he could turn to them for their knowledge and advice around building upon his research.
From two steps to one
Current tests include the ‘gold standard’ PCR (polymerase chain reaction) test and the more rapid but less accurate lateral flow tests. The former takes more than an hour to process, while the latter still requires 30 minutes to get a result. PCR tests use a reverse transcriptase enzyme to convert RNA to DNA as the first step, then use a DNA polymerase enzyme to copy the DNA, ‘amplifying’ the material many times over to detectable levels.
The method developed by Jake – Reverse Transcriptase Free EXPAR (RTF-EXPAR) – uses very short, single strands of DNA (Binder DNA) that recognises and binds to the viral RNA, plus an enzyme that recognises the DNA once RNA is present and cuts a short section. That releases the RNA to bind to more Binder DNA, and the cycle repeats.
The entire test can be run on standard laboratory equipment at lower temperatures, which Jim describes: “This is an extremely promising approach to developing a rapid, accurate test which could increase NHS testing capability by up to five times.”
Pride in the city
The final member of the team is Professor Andrew Beggs, from the University’s Institute of Cancer and Genomic Sciences. He also evaluates diagnostic tests for the Department of Health and Social Care and is now supporting Jake to take the test through to the next stage.
As well as seeing the potential in hospitals to identify the virus, Andrew sees the importance of such a rapid test in opening up the economy – offices, sport, retail and entertainment. Andrew explains that: “Mass events like next year’s Birmingham 2022 Commonwealth Games and big concerts and sports gatherings would benefit enormously from having a rapid and reliable test for competitors and visitors, with almost instant results.”
This potential has made the story of global interest but the focus on the West Midlands was no surprise to Tim: “Birmingham has the largest collection of med-tech companies in the UK, so it’s a good place to do it.” The importance of the story and connection to the city, the university, and Jake has also inspired others, as Tim adds: “My undergrads were asking me to give updates on Jake’s assay; they requested extra tutorials.”
Trialling the technology
Jake has worked with University of Birmingham Enterprise to file a patent application, seeking funding for the next step – testing thousands of samples to confirm the findings before being adopted by the NHS. The results are looking promising; no cross reaction with the majority of other respiratory pathogens and better sensitivity than PCR and loop-mediated isothermal amplification (LAMP) tests. The team expect that, in the long-term, the use of the RTF-EXPAR technology will be extended for use with other RNA-based viruses and infectious agents, as well as other diseases, including cancer.
“I would say to have a go. We didn’t know this would work, but we gave it a go. If you get caught up in making it work perfectly in theory, you slow everything down. We had about 80% of a plan, and then we tried it. It quickly evolved into something really good. If we kept thinking about it, we could still be thinking about it today,” – Jake Carter
“Not just funding projects as they come through, but funding the scientists to get together, is cheap. In any emergency, the limitation on what comes out is the communication between people. The more people talk, the more likely a solution will be found,”- Prof Tim Dafforn