New technology simplifies production of biotech medicines

The final step in the production of a biotech medicine is finishing with the correct sugar structure. This step is essential for the efficacy of the medicine, but it also makes the production process complex and expensive.

But Leander Meuris, Francis Santens and Nico Callewaert, based at life science research institute VIB at the University of Ghent (VIB/UGent) have developed a technology that shortens the sugar structures while retaining the therapeutic efficiency. They believe this technology has the potential to make the production of biotech medicines significantly simpler and cheaper. Their research is published in the journal Nature Biotechnology.

Nearly all biotech medicines are proteins. Most of these medicines contain a mixture of complicated sugar structures that are attached to the protein. While these sugars are important for the mechanism of the medicine their complicated structure can cause problems during production. This makes the process expensive and often results in a mixture of the same protein with different sugars attached. In some cases, only a few of the many sugar forms are suitable for the treatment, meaning that a part of the production and treatment efficiency is lost.

This technology has allowed us to solve an old biotech problem

The proteins that are used as biotech medicines are produced by living cells and Meuris and Callewaert have altered these production cells so that they truncate the sugar structures to a smaller shape. To achieve this they added an enzyme obtained from a fungus, which truncates complex sugars, to the production cells. The stump that remains after truncation is then expanded by the cells to form two similar structures that are suitable for therapeutic applications. Surprisingly, these production cells grow perfectly and continue to produce the therapeutic proteins.

'This technology has allowed us to solve an old biotech problem,' says Callewaert. 'Since the 1990s, nearly everyone has been working to make the sugar synthesis in biotech production cells as similar to human cells as possible. This is a very difficult task, because there are so many steps in this synthesis pathway. We have been able to create a ‘detour’ in this synthesis pathway in a fairly simple manner, making the pathway much shorter and simpler.'

Meuris added: 'You can compare it with a pollard willow. The branches of willows are pruned to keep the tree more functional, just like our technology in which we removed the complex branches to make biotech medicines more manageable and in some cases more efficient.'

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