Potential of plants to produce recombinant protein products

Abstract

Plants have great potential as photosynthetic factories to produce pharmaceutically important and commercially valuable biomedicines and industrial proteins at low cost. The U.S. Food and Drug Administration (U.S. FDA) has approved the drug Elelyso (taliglucerase alfa) produced by carrot cells for treatment of type 1 Gaucher's disease in 2012. The commercial potential of biomedicines produced by molecular farming has dramatically improved due to the success of an experimental drug called ZMapp, which has immunological activity in Ebola patients. A cocktail of three monoclonal antibodies was produced in tobacco (Nicotiana benthamiana) plants (Chen and Davis 2016). At present, very few drugs made by this technology have been approved by worldwide authorities such as the U.S. FDA. However, plants have been proposed as a novel paradigm for commercial production of proteins over the next decade. In recent years, leading researchers on molecular farming have given more priority to the area of animal-free therapeutic proteins such as parenteral and oral vaccines. Although plant-based platforms have considerable advantages over traditional systems such as bacterial and animal systems, there are several obstacles to commercial-scale production, especially with regards to improving the quality and quantity of plant-produced biologics and industrial materials. One of the biggest barriers to commercialization of this technology is the intense scrutiny of these new plant varieties by regulatory agencies and the public as well as the high costs associated with their regulatory approval.

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

“…This system has several advantages, viz. low cost, safety (low risk of contamination with animal pathogens), easy scale-up, stability, presence of metabolites, and ability to produce N-glycosylated proteins (Fahad et al, 2015;Yao et al, 2015;Łojewska et al, 2016;Lomonossoff and D'Aoust, 2016;Park and Wi, 2016;Xu et al, 2016;Buyel et al, 2017;Dirisala et al, 2017;Owczarek et al, 2019). Plant-based biologics have expanded to include cancer immunotherapy agents (Chen et al, 2016;Hefferon, 2017).…”

“…The world's first plant-derived IgA mAb that recognizes the surface antigen I/II of Streptococcus mutans (CaroRx TM -an anti-S. mutans produced in tobacco), the predominant cause dental caries, has been licensed in Europe and is used to prevent tooth decay (Larrick et al, 2001;Loh et al, 2017). Biopharmaceuticals produced in plants are at various stages of clinical trials or market implementation (Yao et al, 2015;Park and Wi, 2016;Dirisala et al, 2017;Owczarek et al, 2019 (Owczarek et al, 2019). Human growth hormone was the first recombinant protein produced in transgenic tobacco (Barta et al, 1986;Yao et al, 2015;Loh et al, 2017).…”

Plant Molecular Farming: A Viable Platform for Recombinant Biopharmaceutical Production

“…The technology has rapidly developed, and the potential drawbacks associated with plant molecular farming during their early stages of development, including the need for a high protein expression level and efficient downstream processing, have now been achieved. The advantages of plant expression platforms are cited in several earlier reports showing head-to-head comparisons with other existing platforms (Table 1) [10][11][12][13][14][15][16][17][18]. The key advantages of all plant-based systems are easy cultivation, low expenses, low or no pathogen load, rapid mass production of recombinant proteins, and the ability of the plants to assemble complex proteins with eukaryotic-like post-translational modifications (PTMs) [19].…”

Host Systems for the Production of Recombinant Spider Silk

“…In addition, plant cells have the capacity to accumulate recombinant proteins within specific organelles, aiding both the stability of recombinant proteins and simplifying the purification process [27]. The combination of low up-front costs and the theoretically infinite scalability offered by agriculture add further appeal to the use of plant hosts for recombinant protein production [28]. However, plant systems are still beset with the issue of low expression yields when compared with microbial expression systems, and often produce poorer quality products relative to mammalian expression systems [26].…”