Molecular Pharming is a recent technology used for the large scale production of proteins with therapeutic value in transgenic plants and animals. This technique is cost effective and has received global attention in recent years. The major factors which influence this production system are its cost effectiveness, scalability, flexibility, versatility, and robustness of the system over the conventional production systems. Plants have relative advantage over other expression systems and have been used for the production of several biopharmaceuticals including recombinant vaccine antigens, monoclonal antibodies, and other commercially viable proteins. Hence this production system is conceptualized as Plant Molecular Pharming.

Plant as Biofactories

Plants are utilized for the expression of recombinant proteins for several years since late 1980s, however there were several hurdles for acceptance of it as expression system compared to the microbial production systems due to its usage as food or feed sources as part of the human food chain.  The first plant-based product commercialized was “Elelyso” by Protalix Biotherapeutics for the treatment of Gaucher’s disease in 2012 (Panya and Mohanty, 2015).

Use of plants for production of high-value recombinant proteins ranging from pharmaceutical therapeutics to non-pharmaceutical products such as vaccines, antibodies, enzymes, growth factors, agriculturally important proteins and cosmetic ingredients has made dramatic changes over years and has led to a major paradigm shift in the pharmaceutical sector. A comprehensive list of the biopharmaceuticals produced in plants is reviewed by  Balamurugan et al., 2020 (Table 1).

Plant transformation strategies

For production of biopharmaceuticals, the technology used are production of stable nuclear transgenic plants, transplastomic plants, transient expression using a plant virus (Tobacco Mosaic Virus) and transient expression via Agrobacterium infiltration (Floss et al., 2007).

The target DNA which has the genetic information needed to make the pharmaceutical is transformed using the plant virus or Agrobacterium or into plant genome directly. The ribosome machinery decodes the target DNA and produce recombinant protein along with other plant proteins in large quantities (Fig.1). These pharmaceutically active substances can also be made to express in a bioreactor system.

Advantages of plants as expression systems

The major advantages of plant-based systems are

§ easy cultivation

§ low expenses

§ Plants do not carry pathogens that might be dangerous to human health          

§ rapid mass production of recombinant proteins

§ the ability of the plants to assemble complex proteins with eukaryotic-like post-translational modifications (PTMs).

§ Easy storability and transport to even remote areas since the seeds and fruits serve as sterile packaging containers for the valuable therapeutics etc.

 Table 1. Selected list of biopharmaceuticals expressed in plant system