Plants as Factories for Human Pharmaceuticals: Applications and Challenges

Abstract

Plant molecular farming (PMF), defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc) produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome), preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans) and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.

Emerging technologies to achieve oral delivery of GLP-1 and GLP-1 analogs for treatment of type 2 diabetes mellitus (T2DM)

“…In recent years, there has been increasing use of plants to produce high-value biotherapeutic agents such as cytokines, enzymes, edible vaccines and antibodies [30,31,33]. The carrot cell-derived human glucocerebrosidase enzyme (GCB) has been approved by FDA and maketed under the trade name Elelyso™, for the treatment of patients with Gaucher disease [34].…”

Vacuolar deposition of recombinant proteins in plant vegetative organs as a strategy to increase yields

“…1 Recombinant protein yields are widely variable and depend on numerous factors such as plant species, promoter, enhancers, incorporation of intron sequences, mRNA stability, 5 0 and 3 0 untranslated regions, codon usage, protein folding and stability, etc. 2,3 Different technologies have been developed to increase transcription efficiency, mRNA stability and translation effectiveness and to improve protein folding and stability. 3,4 Among the post-translational factors, subcellular localization is of particular interest as it has a profound impact on protein yields.…”

“…2,3 Different technologies have been developed to increase transcription efficiency, mRNA stability and translation effectiveness and to improve protein folding and stability. 3,4 Among the post-translational factors, subcellular localization is of particular interest as it has a profound impact on protein yields. 2 In leaves, some complex proteins are usually targeted to the apoplastic space where proteolysis can occur [5][6][7] ; alternatively if Golgi post-translational modifications are not necessary to obtain a fully active molecule, they can be retained on the endoplasmic reticulum (ER).…”

“…10 Foreign proteins sorted to these special compartments accumulate in large amounts and in stable forms for long periods of time. 3,11 Deposition of recombinant proteins in central vacuoles of vegetative tissues has initially been considered inadequate since this compartment was expected to be hostile. For example, green fluorescent protein is unstable in the central vacuole of Arabidopsis thaliana leaves or cultured cells since light triggers vacuolar acidification and proteolysis by cysteine proteases.…”

“…Accumulation of foreign protein in reproductive seed storage compartments has been reviewed elsewhere. 3,11 Selected examples of vacuolar sorted recombinant proteins in vegetative tissue are presented in Table 1, and we shall highlight their particularities.…”