Turning plant seeds into medicine factories

29 April 2016

​Thanks to a collaboration between two VIB/UGent research groups, Ann Depicker and Nico Callewaert have achieved a biotechnology breakthrough. The GlycoDelete technology, which simplifies the production process for biotech medicines, was originally developed in mammalian cells by Nico Callewaert. By jointly applying this technology to plant seeds, the researchers have demonstrated that plant seeds can serve as a medium for the inexpensive and large-scale production of biotech medicines. The results of their research were published in Nature Biotechnology.

Why is plant-based production of medicines such an important milestone?
Nico: “Because of the major advantages. First of all, plants don’t need expensive fermenters and control systems, so it is much easier and cheaper to grow them. Second, you can store the dried plant seeds containing the protein of interest for years at room temperature. When you need the protein, all you have to do is isolate it from the seeds. This is a huge advantage, as it enables
stockpiling of pharmaceutical proteins that could treat epidemic or rapidly spreading infections such as the recent Ebola outbreak. In those cases, production capacity is often a bottleneck.”

A crucial hurdle were the sugar chains attached to plant-produced proteins.
Ann: “Yes. Plants produce different sugar structures than human cells do. When eating plants, this usually does not pose a problem, since the sugars are digested. However, if we inject plant-based biotech medicines into the bloodstream, those plant-specific sugars will be identified as foreign by 25 to 50% of the population, resulting in a severe allergic reaction. This problem has long hampered the wider use of plants to manufacture biotech medicines.”

Nico, how did your team come up with a solution?
Nico: “In 2014, we developed GlycoDelete technology, which shortens the undesirable sugar structures. This solves the issue completely, by making the sugar chains homogeneous and removing the plant-specific immunogenic epitopes.”

“The simplicity of the modification makes an industrial approach possible and could lead
to the inexpensive large-scale ‘pharming’ of medicines using plants.” - Ann Depicker

How was the technology tested and what are the next steps?
Ann: “We let unmodified Arabidopsis seeds and seeds with the GlycoDelete mutation both produce a specific test protein. Rabbits that were injected with the proteins containing plant-specific sugar structures displayed an undesirable immune response, but that response was absent upon injection with the truncated proteins from the GlycoDelete seeds. What’s more, the GlycoDelete modification did not hinder the seeds’ growth. The application of GlycoDelete to plants opens the door to many promising advances. Now we’re working on transferring a next-generation version of our joint technology to plant species that produce protein-rich seeds in large quantities. The simplicity of the modification makes an industrial approach possible and could lead to the inexpensive largescale ‘pharming’ of medicines using plants.”

Piron et al., Nature Biotechnology 2015

Ann Depicker and Nico Callewaert (VIB/UGent)