Antibodies from Plants : part I

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Throughout the past four decades the field of plant-made recombinant antibody (PMAb) production thrived amidst trials and tribulations. The rapid progress in novel techniques related to PMAb manufacturing is mainly due to technological advancement and growing market demand. The purpose of this brief review was to discuss the modern technologies used for PMAb production. Compare and contrast the strengths and limitations of these modern technologies and detail the recent applications using examples in the field of research and therapy.

A bit from the history

In the past two decades the concept of plant-made recombinant antibodies (PMAbs) has been gaining significant attraction as a promising therapeutic solution in comparison with the classic expression systems due to its cost-effectiveness, scalability and robustness (Shanmugaraj et al. 2020). The concept of PMAbs came into light with the seminal work of Hiatt and colleagues (1989): a discovery of fully functional antibodies derived from tobacco plant, which became a driving force for succeeding researchers (de Neve et al. 1993; Hein et al. 1991; During et al. 1990). During the past decades several advancements of the recombinant protein and associated systems were evident as shown in the Figure along with several pitfalls and barriers.

Key Milestones of Plant Antibody Production (1980–2020)

Plant Molecular Farming

Plant molecular farming is the production of recombinant non-native proteins in plants; a new technology that revolved the traditional techniques due to its cost-effectiveness, safety and scalability (Fischer and Buyel 2020; Frenzel et al. 2013; Shanmugaraj et al. 2020). The targets of interest are either therapeutics or non-therapeutics, which were primarily produced by mammalian, yeast or bacteria cells now manufactured using cutting-edge plant-based platforms (Burnett and Burnett 2020; Donini and Marusic 2019; Shanmugaraj et al. 2020).

The process of Plant Molecular Farming (Singh et al. 2016)

Plant Expression Systems

Transient expression has emerged as the preferred production method of recombinant proteins due to high speed, scalability, adaptability and safety (Moon, et al. 2020; Sainsbury and Lomonossoff 2008). For instance, Zischewski et al. 2016 reported one of the highest antibody biomasses in less than a week after production (> 2 g kg 1). Transient expression relies on agroinfiltration where expression vectors containing the gene-of-interest are transferred to plant cells via Agrobacterium tumefaciens (Das, et al. 2020; Shanmugaraj et al. 2020). Furthermore, experiments by (Norkunas, et al. 2018; Sainsbury and Lomonossoff 2008) added more value to current transient systems enhancing its productivity.

Plant transformation is the process of introducing a foreign gene into a plant genome to create a transgenic plant. One method of delivering foreign genes into plant cells is by using the bacteria Agrobacterium tumefaciens. In this process, a foreign DNA fragment is inserted into a native Ti plasmid, which is then reinserted into the bacterial cells. Agrobacterium uses horizontal gene transfer to deliver the DNA fragment into the plant chromosome, allowing transgenic plants to express this gene. (Zhang, 2006)

part II of this article will focus on recent plant antibody applications.