Plants have significant potential for the production of biologics due to their low cost of growth and scalability. Almost all biologics are currently produced in mammalian cell cultures or biofermentation which have several limitations including high costs and safety concerns. Plants offer a safe, effective and affordable alternative for large-scale production of various proteins and biologics including antibodies, vaccines and enzyme replacements.
Advantages of Plant-Based Systems
Some key benefits of plant-based expression systems for biologics include:Low Cost of Production: Plant-Based Biologics have low requirements for growth and can be cultivated on a large scale. This results in significantly lower production costs compared to expensive fermentation and cell culture methods. Production in plants is estimated to be 4-10 times cheaper than standard recombinant methods.Scalability: Greenhouses and field cultivation allows for massive scalable production in a relatively small footprint of land. Growth of biologics in plants is easily scalable whereas expanding fermentation capacity requires large capital investments and time.Fast Growth: Plants have rapid growth cycles ranging from a few weeks to a few months allowing for multiple harvests in a single year. This enables continuous, high-volume production of recombinant proteins.Ability to Glycosylate: Most plants have the ability to glycosylate proteins similarly to mammalian systems. This allows production of biologics like antibodies with human-like glycosylation patterns important for efficacy and safety.Safe Expression Systems: There are no risks of contamination from human or animal pathogens. Plants do not harbor the same types of viruses or other pathogens that could potentially infect humans or vertebrate cell culture systems.No elaborate processing: Minimal processing is required to purify and formulate plant-made pharmaceuticals. Extraction and purification of biologics from plant biomass is simpler than from microbial or mammalian systems.
Examples of Plant-Based Biologics
With advances in plant molecular farming, several Plant-Based Biologics are now being produced experimentally or commercially in plant systems. Some key examples include:- Human Growth Hormone: One of the first biologics produced in plants. It has been successfully tested for safety and efficacy in several clinical trials.- Avian Influenza Virus Vaccine: Plant-produced flu vaccine has been shown to induce protective immune responses in animal models. It provides a more scalable option than egg-based production methods.- Antidiabetic Insulin: Both regular and long-acting versions of human insulin have been synthesized in plants. It holds promise for affordable management of diabetes worldwide.- Monoclonal Antibodies (mAbs): Therapeutic mAbs targeting cancer, autoimmune diseases and infections have been synthesized in plants. Production provides human-like glycosylation without animal-culture requirements.- clotting Factor IX: Hemophilia B patients have been treated successfully with plant-produced coagulation factor IX in early stage clinical trials establishing plant feasibility.- Snake Venom Antidotes: Plants have been used to produce antidotes against snake venom toxins that are difficult to source by conventional means.
Advancing Plant-Based Expression Systems
While significant progress has been made, further research is ongoing to expand the range of biologics that can be produced in plants and optimize production parameters:- Emerging Hosts: New plant species like lemna minor duckweed and chicory are being evaluated that may offer advantages over traditional tobacco, carrot and others.- Subcellular Targeting: Directing proteins to different plant cell compartments like chloroplasts and endoplasmic reticulum can improve yields and quality attributes.- Post-Translational Modification: Understanding plant glycosylation and developing strategies to humanize PTM patterns will enhance efficacy of certain biologics.- Stable Transformation: New transformation techniques and use of stably transformed plant lines eliminates dependence on transient expression systems and allows multi-year stable production.- Scale-up and Processing: Streamlining scale-up, extraction, purification and analysis processes will make plant-based systems more commercially viable and cost-effective.
Plant-Based Biologics Future Prospects and Challenges
Significant research interest and progress in plant molecular farming clearly establish plants as a promising platform for low-cost, safe and scalable biologics manufacturing. As production challenges are addressed, more plant-produced therapeutics are expected to enter commercialization in the coming years especially for developing countries. Key stakeholders will need to continuously address regulatory, intellectual property and public acceptance issues to realize the full socio-economic advantages of this innovative approach. Overall, plant-based biologics hold exciting future possibilities for more affordable and accessible healthcare worldwide.
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