VIB/UGent researchers enable safer production of biotech medicines using plant seeds

1 December 2015

The VIB and Ghent University professors Ann Depicker and Nico Callewaert have achieved a significant biotechnology breakthrough that targets the production of medicines. The GlycoDelete technology, which simplifies the production process for biotech medicines, was originally developed in mammalian cells by prof. Callewaert. By jointly applying this technology to plant seeds, the two researchers have demonstrated that plant seeds can also serve as a medium for the inexpensive large-scale production of biotech medicines. The results of their research were published in the leading scientific journal Nature Biotechnology.

Nico Callewaert (VIB/UGent): “The major advantage of the plant-based method is that seeds containing biotech medicines can be stocked until they’re needed. Here we’re thinking primarily of an epidemic or rapidly spreading infection, such as Ebola or the flu.”

Proteins have been used as therapeutics for decades. These biotechnology medicines are the fastest-growing segment of the pharmaceutical industry. To date, nearly every therapeutic protein has been produced by microorganisms and mammalian cells into which the information required to produce the protein is injected.

Speeding up drug production
These therapeutic proteins have already delivered a treasure trove of new medicines, with a starring role for antibodies. Over the past decade, this type of protein has increasingly been used to treat cancer, autoimmune illnesses and infectious diseases, and researchers keep discovering additional ways to use them. However, it is often very expensive and time-consuming to set up the processes required to produce antibodies in mammalian cells.

Nico Callewaert (VIB/UGent): “For some applications, rapid production is essential: for example, when there is a need for vast quantities of antibodies during an outbreak of an infectious disease such as the flu or Ebola. In cases like these, it would be ideal to have an inventory of these antibodies in dried plant seeds, which can be inexpensively stored for years. Note that these seeds would never be used as food; rather, in an emergency the therapeutic proteins could quickly be purified from them to treat the disease.”

Shortening sugar structures
Antibodies contain a mix of complex sugar structures. These sugars are important for the biotech medicine’s proper functioning.

Ann Depicker (VIB/UGent): “Plants produce different sugar structures than human cells do. If we inject plant-based biotech medicines into the bloodstream, those plant sugars will be identified as foreign to the body by part of the population, evoking an immune reaction. This problem has long hampered the wider use of plants to manufacture biotech medicines. In 2014, however, prof. Callewaert’s team developed a way to efficiently solve this type of issue. Their GlycoDelete technology shortens the undesirable sugar structures.”

Nico Callewaert (VIB/UGent): “It was a natural next step to test our GlycoDelete technology in the plant seeds in which prof. Depicker’s team is able to create biotech medicines. We had 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, as to a foreign substance. That response was absent, however, upon injection with the truncated proteins from the GlycoDelete seeds. What’s more, the GlycoDelete modification did not hinder the seeds’ growth. This solves a problem that has long obstructed the large-scale ‘pharming’ of medicines that contain sugar structures.”

Turning plant seeds into medicine factories
The development of the GlycoDelete technology is itself a major breakthrough, and its application to plants opens the door to many promising advances.

Ann Depicker (VIB/UGent): “Arabidopsis is a model plant that lends itself to the rapid testing of new ideas such as GlycoDelete. 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 GlycoDelete technology is useful for all therapeutic proteins that can function with a truncated sugar structure. The simplicity of the modification makes an industrial approach possible and could lead to the inexpensive large-scale production of medicines using plants.”


Using GlycoDelete to produce proteins lacking plantspecific N-glycan modification in seeds, Piron et al., Nature Biotechnology 2015

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Nico Callewaert is one of the organizers of the upcoming VIB Conference Genome Engineering and Synthetic Biology: Tools & Technologies, held on January 28 and 29, 2016 in Gent, Belgium. More information can be found on the conference website.

Ann Depicker, Nico Callewaert