Abstract
Molecular pharming is a cost-effective, scalable, and safe system to produce high-quality and biologically active recombinant therapeutic proteins. Thus, plants are emerging alternative platform for the production of pharmaceutically relevant proteins such as vaccines, antibodies, antibody derivatives, and some serum-derived proteins. Additionally, plants have also been used to produce bioactive and immunogenic peptides. The efficacy, selectivity, specificity, and low toxicity make them particularly well-suited therapeutic agents for various indications, for instance, cardiovascular and infectious diseases, immunological disorders, and cancer. In the broad range of known bioactive peptides, angiotensin I-converting enzyme inhibitory (ACEI) peptides derived from food proteins have attracted particular attention for their ability to prevent hypertension. So far, several ACEI peptides have been identified in food proteins, mainly in milk, eggs, and plants. The industrial production of ACEI peptides is based on enzymatic proteolysis of whole food proteins, which leads to the release of small bioactive peptides with ACE-inhibitory activity. The problems associated to such procedures, namely, cost and loss of functional properties, have demonstrated the need to develop more straightforward methods to produce ACEI peptides. One viable hypothesis, discussed in this chapter, is to genetically engineer crop plants to produce and deliver antihypertensive peptides.
Highlights
The term “molecular pharming,” blend of pharmaceutical and farming, surfaced in the literature in the 1980s to refer to the production of high-value compounds in Genetic Engineering - A Glimpse of Techniques and Applications transgenic animals
In the broad range of known bioactive peptides, angiotensin I-converting enzyme inhibitory (ACEI) peptides derived from food proteins have attracted particular attention and have been studied the most comprehensively for their ability to prevent hypertension [95]
This study showed that enzymatic hydrolysates of AMC3-containing ACEI peptide (4xVY and Ile-ProPro tripeptides (IPP)) sequences had significant in vivo antihypertensive action [138]
Summary
The term “molecular pharming,” blend of pharmaceutical and farming, surfaced in the literature in the 1980s to refer to the production of high-value compounds in Genetic Engineering - A Glimpse of Techniques and Applications transgenic animals. Imiglucerase, a recombinant form of glucocerebrosidase commercialized under the name Cerezyme®, was already produced in CHO cells In this production platform, the enzyme required subsequent in vitro exposure to mannose residues in order to have biological activity, resulting in a time-consuming and expensive manufacturing process. Glucocerebrosidase is a clear example of a target product in which safety, cost, and downstream processing issues were solved by switching from a traditional platform to molecular pharming Another example that gathered mediatic exposure was ZMapp, a cocktail of three chimeric monoclonal antibodies targeting the Ebola virus surface glycoprotein produced in Nicotiana benthamiana using a hybrid transient expression system, the magnICON system. Instead of facing the red ocean of established pharmaceutical industries [16], molecular pharming is evolving as a disruptive technology that creates its own marketplace by offering rapid drug development and production, unparalleled scalability, unique quality attributes such as tailored glycan structures, individualized therapies, and oral or topical applications of minimally processed plant tissues, reducing downstream costs [17]
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