Phenotypeca win IUK grant for the ‘rapid response to COVID-19’ competition.

June 2020

Next-generation yeast developer, Phenotypeca Ltd, has been awarded funding following a successful application to the “Business-led innovation in response to global disruption” to develop yeast strains for the production of SARS-CoV-2 antigens to detect who has had COVID-19 in the UK population. This addresses an urgent unmet need by UK diagnostic companies and vaccine developers, who Phenotypeca will partner with during the project.

It has become apparent that the UK's diagnostic industry has been unable to respond to the need for the widespread testing required for effective management of the COVID-19 pandemic. This project aims to provide highly productive S. cerevisiae yeast strains for the bulk manufacture of SARS-CoV-2 viral proteins, to act as reference antigens in an effective, low-cost antibody assay, to successfully identify individuals who have immunity to COVID-19.

Parts of the SARS-CoV-2 virion have strong homology to other coronaviruses, making it challenging to produce tests that are both specific and sensitive to COVID-19. To achieve this, Phenotypeca have designed yeast plasmids which will enable the expression of antigens from unique parts of the virus particle's structural proteins, including an exposed region known to bind the human ACE2 receptor.

Baker's yeast has been safely used for over 30 years for the bulk manufacture of biologics, such as insulin and vaccines. It is also relatively inexpensive compared to mammalian systems. Using a genetically diverse collection of natural baker's yeast, Phenotypeca applies a mixture of rational synthetic biology and breeding to generate a billion progeny, from which optimised production strains are selected with beneficial phenotypes for industrial bioprocesses.

Currently, developers of serological assays and SARS-CoV-2 vaccines have a severe supply crisis for reference antigens. Yeast systems have been proven capable of producing coronavirus antigens with the appropriate immunological properties and allow for the bulk manufacture of recombinant proteins, as previously demonstrated with insulins, albumin and vaccines.

“Due to our highly experienced scientific team and strong connections within academia and industry, we are in a unique position to develop a cost-effective expression platform for SARS-CoV-2 antigens”, says Dr Chris Finnis, Research Director of Phenotypeca. “We are delighted to have been chosen out of over 8,600 applicants as part of part this government backed initiative to address the key challenges of COVID-19. We feel that this project could enable assay developers to access a consistent and affordable source of antigens to address the national need.”

This project is a testament to Phenotypeca’s ongoing commitment in improving access to life-saving medicines and promoting sustainable manufacturing using baker’s yeast as the microbial cell factory. This is a traditional technology strength in the East Midlands region which is now linked to UK capabilities in serological assays manufacture. A key constituent of assays for the detection of the antibodies to the SARS-CoV-2 virus are antigens from this virus' structure, acting as a positive control or reference standard, which can be safely produced as recombinant proteins.