Molecular Pharming

“Molecular pharming is the production of recombinant proteins in plants with the intention to use the protein itself as the product, in purified form, crude extracts, or in planta, rather than seeking a change in phenotype, performance, or metabolism.” 2 

Research into production of proteins in plants began in the 1980’s and has been steadily increasing until now3."

The expression of pharmaceutical, and even industrial, proteins in plants is a disruptive technology that offers numerous advantages over the traditional expression systems.

The traditional systems are mammalian cell culture (CHO, HEK cells), E.coli, yeast, insect and live animals (for polyclonal antibodies). These systems are well established worldwide

Plants have been used experimentally to produce recombinant human pharmaceutical proteins since 1989 but the first commercial product was not launched until 20121.

Proteins are divided into various categories depending on their function. For example, antibodies are a class of proteins involved in the immune response to infection. They bind specifically to invading pathogens and target them for destruction within the body. This same binding specificity has been harnessed by life science researchers as a tool, and antibodies are used as reagents in research routinely. According to The Pivotal Scientific Limited Antibody Market Report, “The global market for research antibodies reached approximately USD 1.4 billion in 2018, and the global market for research reagents reached nearly USD 3 billion.”

These antibody reagents are classified as either polyclonal or monoclonal.  Polyclonal antibodies bind multiple epitopes (antigens) and are a heterologous mixture of different antibodies.  These are currently made in live animals by injecting them with an antigen and extracting blood containing the antibodies to the injected antigen.  Monoclonal antibodies are homogenous, more specific to certain antigens, and are produced in large scale systems such as mammalian cell culture platforms.

These traditional processes are very expensive and using live animals raises huge ethical concerns. They are extremely costly to set up, ranging from US$100 million to US$500 million and can take up to 5 years to build, making them unaffordable for emerging economies.  Plant-based expression platforms, however, cost a fraction of this, starting at US$200 000 and can be in full production in under 8 months.

In addition, traditional systems cannot scale-up quickly to meet rapidly changing demands such as disease outbreaks or pandemics, whereas with a plant-based platform there is rapid scalability - we just add more plants. Plant-based platforms are therefore far more flexible, ensuring a security of supply to meet sudden surges in market demand as well as being adaptable to changes in market needs.  We are also capable of responding to uniquely African needs.

The disruptive potential of the plant-based platform creates an equally disruptive product pipeline.  In traditional systems new pharmaceutical proteins can take months to develop.  In plant-based systems we can have new proteins in vials and ready for distribution within weeks of harvesting.

Plant based systems can also produce milligram quantities of novel proteins, or proteins in 'proof of concept' phase.  We can also easily produce custom proteins in small quantities for niche markets.  All that is needed is the genetic sequence, confirmation the plants can express these proteins and the proteins are of acceptable quality, purity and specificity.

Animal, cell-based and bacterial systems are also not ideal for the production of vaccines and therapeutics due to contamination/transfer of zoonotic elements. Plants are therefore the safer alternative for producing therapeutic grade proteins. Plant pathogens are not transferable to humans or animals.

For more information on plant molecular pharming, check out our resource section that contains a list of research papers on the topic. Happy reading! 

References:

    1. Fischer, R., Schillberg, S., Buyel, J. & Twyman, R. Commercial Aspects of Pharmaceutical Protein Production in Plants. Curr. Pharm. Des. 19, 5471–5477 (2013).
    2. Tschofen, M., Knopp, D., Hood, E. & Stöger, E. Plant Molecular Farming: Much More than Medicines. Annu. Rev. Anal. Chem. 9, 271–294 (2016).
    3. Ma, J. K. C. et al. Realising the value of plant molecular pharming to benefit the poor in developing countries and emerging economies. Plant Biotechnol. J. 11, 1029–1033 (2013).
    4. Paul, M., Teh, A., Twyman, R. & Ma, J. Target Product Selection - Where Can Molecular Pharming Make the Difference? Curr. Pharm. Des. 19, 5478–5485 (2013).
    5. Gomord, V. et al. Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol. J. 8, 564–587 (2010).
    6. Conrad, U. Production of vaccines and therapeutic antibodies for veterinary applications in transgenic plants : an overview. 315–332 (2007). doi:10.1007/s11248-007-9095-x
    7. Topp, E. et al. The case for plant-made veterinary immunotherapeutics ☆. Biotechnol. Adv. (2016). doi:10.1016/j.biotechadv.2016.02.007
    8. Hey, C. & Zhang, C. Process development for antibody purification from tobacco by protein a affinity chromatography. Chem. Eng. Technol. 35, 142–148 (2012).
    9. Stephan, A. et al. Simple purification of Nicotiana benthamiana-produced recombinant colicins: High-yield recovery of purified proteins with minimum alkaloid content supports the suitability of the host for manufacturing food additives. Int. J. Mol. Sci. 19, (2018).
    10. Giddings, G., Allison, G., Brooks, D. & Carter, A. Transgenic plants as factories for biopharmaceuticals. Nat. Biotechnol. 18, 1151–1155 (2000).

 

Molecular Pharming