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Inspiring plant cells! Meet Anneli as she talks about the people who inspired her to work with plant cell cultures and why plant molecular technologies will be the ‘first-responder’ in future vaccine R&D

Annelie Ritala is Principal Scientist in Plant Biotechnology at VTT Technical Research Centre of Finland locatedInstitute in EspooHelsinki, Finland, and has been playing a crucial role in Pharma Factory’s ‘work package 6’ to produce complex molecules for a new HIV- neutralising drug using plant cells.

Hi Anneli, would you tell us about why you first chose to work with plants over other organisms used in bio-technology research for ‘drug discovery’?

As a pharmacy student at the end on 1980´s I got interested in plants as source of medicinal compounds. This was mainly due to the great professor Raimo Hiltunen who was one of the best lecturers in the pharmacy department at the University of Helsinki. In a practical lab course, plant cell culture technology was introduced by one of the Finnish pioneers in the field Dr. Kirsi-Marja Oksman-Caldentey. I was completely fascinated on the technology and all the possibilities it holds. I knew immediately that this is something I want to learn more and work with. Then I got a diploma thesis position at VTT in a project where the aim was to improve malting quality properties of barley with genetic engineering. I continued as a PhD student and here I´ve been ever since working in various plant biotechnology and industrial biotechnology projects.

In Pharma Factory there are a range of Plant Molecular Farming technologies being explored, can you tell us a bit more about the ‘plant cell culture’ you are using to produce the new HIV drug in work package 6?

Our expertise lies in utilisation of plant cell cultures as a production host in contained conditions instead of using whole plants in fields or greenhouses. If explained in a simplified way plant cell culture cultivation in large scale is a very similar process than brewing beer in a fermenter. Being able to operate in contained conditions is a great asset particularly when we want to produce medicinal compounds that when wrongly handled can be harmful or even toxic. Use of plant cell cultures in bioreactors brings in benefits from GMP (good manufacturing practise) and regulatory perspectives, too e.g. allowing less variation from batch-to-batch. Furthermore, contained production can be done anywhere and is not dependent on environmental, seasonal or climate conditions.

I understand your research has been quite successful in meeting one of the specific needs of the SMEs in the development of a HIV antibody, can you tell us more about what you have achieved with your research in PF?

In the Pharma-Factory project our role has been to study use of tobacco BY-2 cells as a production vehicle for HIV antibodies. We have long-term know-how with this cell line, and we have been cultivating it in a 1000 litre scale in a steel tank fermenter. Tobacco BY-2 is a very fast growing plant cell culture line that 100-fold multiplies its biomass in a week. This is fast with plant cells but clearly slower than with microbial hosts. However, plant cell cultures have other benefits in being able to synthesize and fold correctly very complex molecules like antibodies accurately and efficiently. In the Pharma-Factory project, we have managed to produce in tobacco BY-2 cells HIV-antibodies that have been difficult to produce in other host systems.

What does a future with PMF look like? (i.e. what are we aiming for with this technology, why is it important?)

The future of PMF looks good particularly for molecules where there is need for speed and volumes like vaccines. Perhaps the most promising being at the moment the transient expression system in Nicotiana benthamiana as no stable integration of the encoding gene is required. With this transient system enough target molecules can be produced in a month for pre- clinical evaluations, which makes it excellent for fast response pharmaceutical R&D.