Ltd.

Satoshi Ozawa

When joining CellFree Sciences, I had been fascinated by the ability to extract the entire machinery for protein synthesis from wheat germ particles. It fled like having much wider control over one of the key processes of life, thus allowing us to perform protein synthesis with unmatched speed and precision. This fascination proved true, when the wheat germ cell-free protein expression system was used to prepare a set of about 20,000 human full-length proteins now presented on our human protein bead array platform. The studies on human proteins also showed that our eukaryotic expression system using the translation machinery from wheat is more suited to deliver high quality proteins as compared to working with bacterial systems like the most often applied E. colicells. Having such a powerful tool, it was important for me to also bring it to the emergency response against the ongoing pandemic.

The COVID-19 pandemic caused by transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deeply disrupted daily lives around the world causing human tragedy. It continues putting people at risk of a potentially devastating disease. To protect the people, diagnostic testing proved to be essential identifying infected patients and to further monitor the spread of the virus for countermeasures. Here, serological testing is the tool at need for post infection surveillance and possible monitoring large-scale vaccine campaigns. Our wheat germ cell-free protein expression system had already enabled the rapid development and later production of similar serological tests in the past. Thus, it was a natural choice to also apply it in response to the COVID-19 pandemic.

Building on experience from having studied the MERS-CoV virus, the group of Prof. Akihide Ryo at the Department of Microbiology of the Yokohama City University School of Medicine in Japan used our wheat germ system to first express a truncated and full-length version of the Nucleocapsid Protein of SARS-CoV-2 for serologically testing patient sera [1]. This work let to the rapid development of the Cica Immuno-test SARS-CoV-2 IgG device at Kanto Chemical now sold in the Japanese market. The test was for example used in a published study on SARS-CoV-2 antibody (IgG) prevalence in 1603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture of Japan [2]. Based on the experience and successful use of theCica Immuno-test SARS-CoV-2 IgG devise, an automated chemiluminescence assay system was developed for quantitative measurement of multiple anti-SARS-CoV-2 antibodies in close collaboration of the Yokohama City University School of Medicine with Tosoh Corporation and Kanto Chemical. This system can perform 240 serological tests per hour and exhibited 100% sensitivity and specificity on blood samples taken 13 days after the onset of symptoms for an COVID-19 infection [3]. Impressive results that will certainly make this an attractive solution to monitor infections.

All steps from early research, prototyping to production of the final diagnostic tests were fully supported by the wheat germ cell-free expression system from CellFree Sciences: It is like a dream coming true, having such a powerful tool for fast, scalable, reliable support making new diagnostic products in response to the COVID-19 pandemic and possibly other diseases as well. Our cell-free wheat germ system is further used to prepare many more other proteins from the SARS-CoV-2 virus in support of the much-needed development of effective treatments for the disease. We will keep on making our best efforts working for counter measures to bring the COVID-19 pandemic to an end.

We have come a long way to make cell-free protein expression systems as versatile as they are today to address most needs in protein research, product development, and later production of life science and diagnostic products. It had been a great experience to be part of this development and to see today what tools we can provide to medical industries working for the benefits of the people and to support global health.

References:

1. Whole Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus 2 May Cause False-Positive Results in Serological Assays, Yutaro Yamaoka et al., Clinical Infectious Diseases, ciaa637, https://doi.org/10.1093/cid/ciaa637
2. Survey of the current status of subclinical coronavirus disease 2019 (COVID-19), Ikuro Matsuba et al., J Infect Chemother. 2020 Dec;26(12):1294-1300. 2020. doi: 10.1016/j.jiac.2020.09.005. 
3. Development of an automated chemiluminescence assay system for quantitative measurement of multiple anti-SARS-CoV-2 antibodies, Sousuke Kubo et al., medRxiv 2020.11.04.20225805; doi: https://doi.org/10.1101/2020.11.04.20225805