Martin Hirst. Photo: UBC.
Public health authorities around the world are facing a significant challenge: ensuring a large enough supply of reagents to scale-up diagnostic testing for COVID-19. Researchers at UBC, Canada's Michael Smith Genome Sciences Centre at BC Cancer (GSC) and the BC Centre for Disease Control (BCCDC) are working to develop new non-proprietary reagents to support testing in British Columbia. UBC geneticist Martin Hirst, senior scientist at the GSC, is leading the project with support from Genome BC through its Rapid Response Funding for COVID-19 Research program.
How are people tested for COVID-19?
There are a couple ways. One is to test for antibodies produced by the patient in response to infection by the virus. This is useful in retrospect, to learn more about how and where populations of people were infected. The other is to test for the presence of the virus itself, in order to determine if someone is currently infected. We’re focused on the latter, using a method called reverse transcription, quantitative polymerase chain reaction (RT–qPCR) to test for SARS-CoV-2 from nose, throat or saliva samples.
How does RT-qPCR work?
Polymerase chain reaction (PCR) is a technique that causes a very small well-defined segment of DNA to be amplified, or multiplied many hundreds of thousands of times so that there is enough of it to be detected and analyzed (polymerase is an enzyme that synthesizes long chains of nucleic acids). However, viruses such as SARS-CoV-2 do not contain DNA, but RNA and “reverse transcription” is the process used to convert RNA into DNA, which has to happen for PCR to work. The amount of viral DNA is then “quantified” using chemicals that fluoresce more brightly with the presence of more DNA. If the virus is present in a sample from a nose or throat swab, for example, this method will first convert its RNA to DNA and then amplify it to the point that it becomes detectable.
What problem with testing are you aiming to address?
COVID-19 testing in BC involves the extraction of RNA from biospecimens using proprietary platforms, and diagnostic testing using a laboratory developed RT-qPCR test with other proprietary reagents. These proprietary reagents are under increasing global demand—extraction kits and probes are back-ordered, and contaminated testing reagents have been received stemming from an inability of companies to keep up with good manufacturing practices. We need to develop the capacity to develop reagents quickly and at the scale needed to support rapid diagnostic testing on an ongoing basis, until this current pandemic subsides and if or when we face another one like it.
How is your research supporting more testing for COVID-19?
We are using the infrastructure at the GSC, UBC and BCCDC to develop scalable and automated non-proprietary extraction and RT-qPCR workflows for the development of stable reagent supply chains. We are producing reagent formulas and automated workflows, shared initially between the UBC and BCCDC sites and, following qualification, to testing sites in B.C. and across Canada. We are working with STEMCELL Technologies to formulate and produce reagents at scale and documenting our automated workflows under Quality Management Systems to provide as turn-key solutions to testing sites in B.C. and beyond.
Where is this research happening?
Our research is being carried out at sites that are uniquely positioned to respond to this testing crisis with world class molecular diagnostic capability, and the appropriate technical and scientific expertise. Specifically, the work will be carried out at UBC’s Michael Smith Laboratory and the Life Sciences Centre, the GSC at BC Cancer and Public Health Lab at BCCDC.
How will this project impact the current COVID-19 pandemic?
Our research is ensuring a secure supply of laboratory reagents needed in B.C. to maintain and expand its capacity for COVID-19 testing. In the medium term, these reagents will be further validated and production will be scaled-up to meet accelerating testing demands in the province. The establishment of molecular resources, protocols and formulations to support large scale RT-qPCR viral testing will also ensure that Canada is prepared to meet future pandemics, particularly in the case of any disrupted global supply chains. Ultimately, a stable supply of reagents, produced locally, will help ensure testing can meet demands, resulting in enhanced contact tracing and isolation that will ultimately limit transmission and manage the spread of COVID-19.