Abstract

Plant cell suspension cultures have several advantages that make them suitable for the production of recombinant proteins. They can be cultivated under aseptic conditions using classical fermentation technology, they are easy to scale-up for manufacturing, and the regulatory requirements are similar to those established for well-characterized production systems based on microbial and mammalian cells. It is therefore no surprise that taliglucerase alfa (Elelyso®)—the first licensed recombinant pharmaceutical protein derived from plants—is produced in plant cell suspension cultures. But despite this breakthrough, plant cells are still largely neglected compared to transgenic plants and the more recent plant-based transient expression systems. Here, we revisit plant cell suspension cultures and highlight recent developments in the field that show how the rise of plant cells parallels that of Chinese hamster ovary cells, currently the most widespread and successful manufacturing platform for biologics. These developments include medium optimization, process engineering, statistical experimental designs, scale-up/scale-down models, and process analytical technologies. Significant yield increases for diverse target proteins will encourage a gold rush to adopt plant cells as a platform technology, and the first indications of this breakthrough are already on the horizon.

Highlights

  • Industry platforms for the production of recombinant proteins are based mainly on microbes and mammalian cells

  • Plant cell cultures are often successful in the laboratory because they can be grown in well-aerated shake flasks and the products can be extracted in small volumes of buffer, allowing the use of protease inhibitors and other expensive additives that cannot be used at the process scale

  • Plant cell suspension cultures will most certainly become the preferred choice among plant-based systems for the production of high-value recombinant proteins, because they combine the advantages of all other systems

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Summary

Introduction

Industry platforms for the production of recombinant proteins are based mainly on microbes and mammalian cells. The immense diversity of molecular farming systems reflects the fact that recombinant proteins have been produced in many different plant species wherein there is a choice of whole plants or various cell/tissue culture formats (Twyman et al, 2003, 2005).

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