Using plant cells to produce diagnostic and pharmacological proteins—that’s the challenge taken up by the researchers at IgGreen, a funding recipient of UCL’s ‘First Spin-off’ programme. IgGreen’s goal: more ethical, cost-effective production.
Currently, the diagnostic proteins and, more specifically, antibodies that are available on the market are produced using animal cells, a well-tried but limited production method. ‘Animal cells used for this kind of production are expensive, have a limited lifespan and require using foetal bovine serum, which is ethically problematic’, says Bertrand Magy, a researcher at UCL’s Institute of Life Sciences and start-up project manager of the spin-off IgGreen. His solution to avoiding these problems is using plant cells instead. ‘This project is the fruit of more than ten years of fundamental research conducted in the Institute of Life Sciences molecular physiology laboratory under the supervision of Professor Marc Boutry and Dr Catherine Navarre.’
In practice, bioreactor-grown plant cells are used as tiny factories for producing the desired proteins. For the protein generated by this process to interest a diagnostic or pharmaceutical company, the gene responsible for producing it must first be inserted into the plant cell genome. Several plants have proven effective in this type of process: Arabidopsis thaliana, Nicotiana benthamiana and Nicotiana tabacum, the last better known as tobacco.
Boosting plant cells’ yield
‘Our experience shows that it’s altogether possible to use plant cells for this type of production but their yield until recently was too low to be profitable. We had to find a way to increase it.’ To do so, he and his team explored several ways that could be combined to achieve an optimal result:
- Boost expression of the gene responsible for producing the protein. In other words, increase the gene’s work capacity. ‘The more this gene is expressed in the plant cell, the more the latter will produce the desired protein’.
- Increase the number of copies of the gene in the cell to increase in turn the quantity of protein produced.
- Manipulate for greater yield the composition of the cell culture medium, which, in a way, is the factory’s fuel. ‘To do this, we optimise proven media by varying factors such as nitrogen source content, hormones, etc.’
Of course, there’s no miracle recipe that works for all proteins. Each factor in the process will require review for every protein IgGreen produces.
More efficient production
Thanks to several years of research, IgGreen has achieved profitable yields in bioreactors with a four-litre capacity. ‘Our process is getting better,’ explains Mr Magy, ‘especially at producing antibodies, and unlike with animal cells, it has the advantage of being stable over time. Indeed, the animal cells typically used to produce diagnostic proteins decline in productivity in 10% of cases, which doesn’t happen with IgGreen’s technology. Our production is assured continuously and consistently by the plant’s undifferentiated cells’.
Two companies specialised in marketing proteins used for diagnosing disease have already expressed interest. ‘Currently, we’re working on the production of antibodies and testing their functionality. We still need to assess production on a scale of about 100 litres.’
In the medium-term, the future company plans to build on the 100% animal-free nature of its platform in order to target the therapeutic sector. ‘Indeed, the absence of cells and substances of animal origin guarantees the absence of mammalian pathogens. Thus it’s a safer pharmacological protein production method.’
Business research and development
A particularity of this Walloon Region-financed research project is its entrepreneurial component. Mr Magy’s team isn’t contenting itself with developing an efficient scientific process; it’s also building a company. ‘Parallel to the scientific component, we have to work on IgGreen’s business plan in order for the project to launch successfully as an independent company. To do this, we’ve surrounded ourselves with business developers who share their knowledge and network.’ Le project won the Prix spécial du public (‘Audience Award’) at the 2015 Start Academy, a student entrepreneurial competition organised by Solvay Entrepreneurs. The company’s creation is planned for late 2016.