Plants have emerged as a viable alternative platform for the production of biologics. Many biopharmaceutical drugs today including monoclonal antibodies, vaccines and clotting factors have traditionally been produced in mammalian cell culture systems or recombinant microorganisms like E.coli. However, plant-based expression systems offer several advantages over these traditional platforms for production of certain biologics.
Advantages of Plant Systems for Plant-Based Biologics Production
Some key advantages that plant systems provide for biologics production include:
Scalability and Lower Cost of Production: Plants have very high biomass yields and can be cultivated on large tracts of agricultural land at lower costs than cell culture systems. Billion doses of vaccines or therapeutics can be produced from an acre of land, bringing economies of scale. Production costs using plant-based systems are estimated to be 5-10 times lower than traditional fermentation or cell culture methods.
Ability to Perform Eukaryotic Post-Translational Modifications: Plant-Based Biologics like tobacco, certain crops and moss species have the ability to perform eukaryotic post-translational modifications like glycosylation, phosphorylation and disulphide bond formation which are important for the efficacy and safety of many protein therapeutics. This makes plants a suitable platform for complex biologics.
Avoidance of Pathogens: Plants do not host human or animal pathogens so there are no risks of transferring viruses, prions or other infectious agents during production. This helps avoid downstream safety issues during manufacturing and administration to patients.
Thermo-Stability and Ease of Storage/Shipping: Many proteins produced in plants have been found to have improved thermo-stability compared to microbial or mammalian cell culture produced versions. This makes transport and long-term storage at varied temperatures much easier for plant-made products. It also simplifies distribution in tropical and developing countries with limited cold chain logistics.
Expression of Multi-Subunit and Mosaic Proteins: Certain complex proteins composed of non-covalently associated subunits or mosaic proteins can be produced as a single polypeptide in plants and self-assemble correctly. This overcomes issues with combining individually produced subunits during manufacturing of microbial or cellular biologics.
Edible Vaccines and Oral Delivery: Leaves, seeds or fruits from transgenic plants can act as an ideal edible vaccine for certain infections. The natural mucosal immune induction following oral delivery through edible plant parts is a unique advantage over injectable vaccines.
Plant-Based Biologics: Various Plant Species for Production
Different plant species are being explored as hosts for molecular farming of various biologics:
Tobacco Plants: Tobacco (Nicotiana tabacum and Nicotiana benthamiana) is the most widely studied and established system for Plant-Based Biologics production. It has high biomass yields, techniques for agroinjection, transient expression are well optimized and many candidates have been tested at pilot and commercial scale. Examples include ZMapp Ebola virus drug.
Legumes: Soybean, pea, alfalfa and clover are valuable leguminous crop plants evaluated for applications in molecular farming. They have large seed storage tissues for high level accumulation of target proteins. The potential for developing edible vaccines is also being studied.
Cereals: Maize, rice, barley are major food crops assessed for production of oral therapeutic proteins or vaccines delivered through transgenic seeds or grains. Regulatory norms are permissive compared to tobacco and researchers are exploiting endosperm, aleurone and embryo tissues.
Moss Species: P. patens is a model plant with simplistic structure, rapid life cycle and ability to perform eukaryotic modifications. It can express and accumulate complex multi-subunit products in the chloroplast or secretion organelles like the apoplast. Examples include MVA (monoclonal virus-like particles vaccine).
Carrot and Lettuce: These edible plant species are important for oral delivery of therapeutic proteins and vaccines through transgenic fruits and leaves. Early studies showed feasibility of producing antibodies, cytokines and human blood factors. Commercial usage is still awaited though.
Bioencapsulation for Oral Tolerance and Delivery: Certain transgenic plant tissues are being engineered to survive stomach acid but selectively break down or ‘bioencapsulate’ therapeutic payloads in the duodenum or gut tissues for oral tolerance induction and treatment of conditions like inflammatory bowel disease.
Cell Suspension Cultures: Hairy root cultures from plant species like Nicotiana tabacum, Anthirrhinum majus, Medicago trunculata are being studied as an alternative to whole plants for consistent, scalable bioprocessing environments resembling fermenters. Yields can reach 1-3 grams per liter of active protein.
Regulatory and Commercial Developments
GM plants and their derived products are regulated for safety and efficacy evaluation. Guidelines are now evolving on a case-by-case basis considering scientific evidence and risk assessment principles.
Key regulatory milestones:
– First approval of MEDUSA transplastomic tobacco for field trials was received in Canada (2001).
– Phase 1 clinical trial approval and testing of plant-derived monoclonal antibody was granted by FDA (2006).
– First plant-made pharmaceutical approval was granted in EU for glucocerebrosidase enzyme for Gaucher disease produced in carrot cells (2006).
– USDA/APHIS no longer regulates GM plant products that do not contain plant material like purified proteins (2018).
Commercial activities:
– Several clinical-stage candidates now exist for conditions like diabetes, cancer, Ebola produced in crops like tobacco and moss species.
– Canada’s biotech company produces recombinant clotting factor IX for hemophilia used by ~2000 patients annually since 2009.
– Large agriculture firms are partnering to advance plant-made monoclonal antibodies to market for diseases like COVID-19 and veterinary use.
Plant-based systems have emerged as an attractive platform to produce various categories of biologics for applications in human and animal health. Commercial usage is increasing as technology platforms mature and safety/efficacy of products.
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Priya Pandey is a dynamic and passionate editor with over three years of expertise in content editing and proofreading. Holding a bachelor’s degree in biotechnology, Priya has a knack for making the content engaging. Her diverse portfolio includes editing documents across different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. Priya’s meticulous attention to detail and commitment to excellence make her an invaluable asset in the world of content creation and refinement.
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