Genetic engineering is poised to help biopharma realize the potential benefits of commercial-scale, plant-based protein production, according to a leading researcher.

The idea of making therapeutic proteins in plants is not new. The FDA approved Elelyso (taliglucerase alfa)—a treatment for Gaucher’s disease that is expressed in engineered carrot cells—in 2012.

The rationale is simple: plant cells are free of some of the problems associated with mammalian-, insect-, bacterial-, or yeast-based systems. For example, microbial cells cannot produce proteins that require defined oligomerization. Likewise, mammalian cells are unsuitable for the manufacture of toxic proteins.

Plant-based expression systems, in contrast, have the machinery required for complex protein formation and can sequester toxic molecules.

Despite this, beyond Elelyso and a few vaccines—notably the SARS-CoV-2 jab Covifenz— to date, plants have not been widely used for commercial-scale protein production.

One of the most commonly cited issues is that plant glycosylation mechanisms differ from those of mammalian cell-based expression systems.

But, this issue can be overcome using genetic modification, according to Johannes Buyel, PhD, professor at the Institute of Bioprocess Science and Engineering at the University of Natural Resources and Life Sciences, Vienna, Austria.

“You can express human glycosyltransferases in plants that will add the same sugar residues as in humans. Glycosylation in plant expression systems is only a concern for those who have not looked into it.

“In fact, plant glycosylation can be advantageous as seen for glucocerebrosidase, where human glycosylation reduces serum half-life compared to the plant counterpart,” Buyel tells GEN.

Cost benefits

And there are other benefits of plant cell expression systems, notably their impact on the cost of goods sold (COGS).

Buyel says, “There are several cost advantages. Cultivation of plants is much cheaper than that of animal cells. For example, 1 L of plant cell culture medium costs around 10 cents while 1 L of mammalian cell culture medium costs in the €150–250 range.”

There are also potential productivity advantages, according to Buyel, who points to the relative ease with which plant-based production can be scaled up as a major benefit.

“Compared with mammalian cell-based expression systems, the yield for plant-based production is often lower. However, the scalability of plant systems is better, as you can use greenhouses instead of costly bioreactors made of stainless steel or disposable bioreactors.”

In addition, Buyel says, although investment would be required to establish greenhouses or vertical farms, all downstream processing operations can be carried out with technology used for mammalian cell-based expression systems.

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