For mass protein production, try moss

Dow Chemical has teamed up with Germany's greenovation Biotech to develop ways of manufacturing therapeutic proteins such as monoclonal antibodies in plants.

The Freiburg-based company is developing ways to use plants to make proteins with glycosylation patterns - the glycan or sugar side chains that are part of a protein's structure - that more closely resemble the human form. This is one of the primary hurdles to overcome when using non-mammalian production systems.

Currently, most therapeutic proteins must be produced in mammalian cell lines, and this is not only time-consuming, but also requires a significant investment in research (on cell lines and reagents, for example) and manufacturing capacity. One solution is to use non-mammalian cell lines, but an obstacle here is that the protein products do not have the same structure as those made in mammalian cells.

Many high-value therapeutic proteins must contain specific glycan or sugar structures to be fully effective and work safely in the human body. Glycoproteins produced by plants have structures which are similar but not identical to those produced by mammalian systems. A primary goal of the companies is to enable production of therapeutic antibodies in a moss system that are fully comparable to those produced in mammalian cell systems.

Using plants to produce biopharmaceuticals is a key strategy for Dow​. Earlier this year, the company entered into an agreement​ to manufacture a potential drug for cancer in transgenic plants developed by Sunol Molecular. The agreement covers production of the protein in plants and a comparison with a version grown in mammalian cell culture.

And in 2002 Dow acquired key patents in glycosylation and began collaborating with Plant Research International of Wageningen, the Netherlands, to speed development of therapeutic proteins with mammalian-like glycan structures in transgenic plants.

In the latest project, greenovation​ will license selected Dow intellectual property covering certain modifications of glycosylation patterns in plants, and Dow will receive greenovation's data on its progress of such work in moss. No financial details are being released.

Research will focus on optimising galactosylation, the major step for achieving mammalian-like glycosylation for monoclonal antibodies. The German company has already developed a way of knocking out plant-specific glycosylation, according to Dr Sabrina Wagner, greenovation's CEO.

"Dow's know-how and experience in modifying plant glycosylation patterns ideally complements our own work in this field,"​ she said.