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What do you think about engineering plants for the production of biopharmaceuticals?

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Andrew Muchlinski
Andrew Muchlinski Aug 04, 2020
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This session is designed to open a collaborative discussion on the use of genetically engineered crops for the production of valuable pharmaceuticals. Current production methods are slow and expensive, but is this a safe and sustainable alternative?

Genetic engineering of plants can be used to facilitate the production of important pharmaceuticals. Such examples include hormones, vaccines, antibodies and natural products. However, the controversy over the safety and efficacy of this production mechanism remains high. This is primarily due to the possibility of these pharmaceuticals entering the food chain via cross-pollination with non-GMO plants. In addition, there is concern over resource usage by designating high-quality farmland for the production of non-food items. Due to less stringent regulation of GMO crops in the USA, and cheaper costs associated with using GMO plants for drug production, it is likely this industry will continue moving forward.

I intend this to be a very broad discussion, but some prompts below may help guide us forward.

Given the state of the global COVID-19 pandemic, would you support the idea of producing vaccines in plants if it proved to be a faster and cheaper method?

As the USA is rather unique globally in their looser GMO regulations, and will likely continue forward with this production process, do you expect other countries to follow suit?

Farmers have been increasingly struggling due to volatile food prices and increased frequency of drought, pests, and disease. This would likely give them a substantial avenue for increased profits. Is that alone enough to justify this practice?

[1]Daniell H, Streatfield SJ, Wycoff K. Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci 2001; 6:219–26.

[2]D.A. Goldstein, J.A. Thomas, Biopharmaceuticals derived from genetically modified plants, QJM: An International Journal of Medicine, Volume 97, Issue 11, November 2004, Pages 705–716.

[3]Giddings G, Allison G, Brooks D, Carter A. Transgenic plants as factories for biopharmaceuticals. Nature Biotechnol 2000; 18:1151–5.

Creative contributions

Start the plant pharms, but first solve these riddles:

Subash Chapagain
Subash Chapagain Oct 05, 2020
It would indeed be a timely strike if we could optimize the process and start producing vaccines against SARS-CoV-2 at this point of time by using plants as the production systems. In theory, and also to some extents in experimental practice, this is quite achievable. However, to be confidently routing for this biotechnological marvel, we have to first address some challenges:
  • How to eliminate the possibility of unintentional and unwanted contact and contamination?
This problem pertains to any other GM plant as well. This might be even more problematic if the chosen plant species have invasive characteristics.
  • How to establish universal standards for vaccine-producing plants?
Like any other regular industrial practice, the production of vaccine using plants should also have a gold-standard reference system. However, it has been difficult so far to assess the relative performance of different crops for industrial/pharmaceutical molecular farming. To develop a standard model of production, the same proteins need to be produced in a range of host using a ‘standardized’ expression construct. This requirement in itself becomes rate-limiting because the performance of an expression construct across species is difficult to judge as the same promoter may have different intrinsic activity and specificity in different genetic backgrounds .
  • How to minimize the loss of produced biomolecules/proteins while using plants as producers?
In a study that examined the production of scFv antibody in transgenic plants , it was observed that after eighteen months in storage, 50% of total functional antibodies were lost. Hence, it is just not enough to establish a high-level protein expression system for good yield in plant-based production systems, there should also be a full-proof efficient plan for recovery of recombinant proteins from the plant tissues.
  • How to decontaminate the produced proteins from other interfering phytochemicals, and from proteolysis?
When we use plants as producers of the vaccines (or recombinant proteins), we have to keep in mind that plants are full of phytochemicals. For example, when we use tobacco plant as a production system, the high content of nicotine and other alkaloids need to be removed first during the downstream processing post-harvest. Another constraint is that since the proteins expressed in leaves tend to be less stable ad unprotected from proteolytic degradation, we must process the plants right after harvest and go for purification steps .
  • How to keep the native structural and functional in the recombinant proteins, ensuring zero unwanted immunogenicity?
Though plants share a lot of similarities to other eukaryotes in terms of protein expression and synthesis, it must be noted that there are some crucial discrepancies in posttranslational modifications, specifically covalent linkage of sugar chains in the mature proteins . Posttranslational maturation can have a significant effect on protein accumulation; if the recombinant proteins are not properly cleaved or conformed, proproteins instead of mature proteins that might drastically hamper the objective of production. Moreover, differences in the glycosylation patterns of the produced proteins in plants and humans raise the concern regarding unwanted immunogenicity of plant-specific complex N-glycans, present in the heavy chain of plant-derived proteins . Hence, whether recombinant proteins with plant N-glycans are immunogenic in humans should be first made clear prior to going for production.

[1]Inaba, Y., Zhong, W. Q., Zhang, X.-H., and Widholm, J. M. 2007. Specificity of expression of the GUS reporter gene (uidA) driven by the tobacco ASA2 promoter in soybean plants and tissue cultures. J. Plant Physiol. 164: 824–834.

[2]Fiedler, U., Phillips, J., Artsaenko, O., and Conrad, U. 1997. Optimization of scFv antibody production in transgenic plants. Immunotechnology 3: 205–216.

[3]Bischoff, F., 2004. A top-down view of molecular farming from the pharmaceutical industry: requirements ad expectations. In: Molecular Farming: Plant-Made Pharmaceuticals and Technical Proteins, 267–287. Fischer, R., and Schillberg, S., eds., Wiley-VCH, Weinheim, Germany.

[4]Saint-Jore-Dupas, C., Faye L., and Gomord, V. 2007. From planta to pharma with glycosylation in the toolbox. Trends Biotechnol. 25: 317–323.

[5]Chargelegue, N. D., Drake, P. M. W., Obregon, P., and Ma, J. C. K. 2005. Production of secretory IgA in transgenic plants. In Molecular Farming: Plant-Made Pharmaceuticals and Technical Proteins, 159–169. Fischer, R., and Schillberg, S., eds., Wiley-VCH, Weinheim, Germany.

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