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.

Highlights

  • The production of plant-derived pharmaceuticals has attracted great interest

  • Additional Ebola patients were unable to receive the treatment due to an insufficient supply of ZMapp. This is unfortunate since it is the only drug to date that has been effectively used to treat patients infected with the Ebola virus, even though it has not been approved by the U.S Food and Drug Administration (FDA)

  • MO, USA) or received USDA approval as a vaccine additive for use in poultry (Dow Agro Sciences, Indianapolis, IN, USA) [1], the current review mainly focuses on Plant molecular farming (PMF) in relation to human pharmaceutical applications

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Summary

Introduction

The production of plant-derived pharmaceuticals has attracted great interest. Mapp Biopharmaceutical Inc., a company located in San Diego, CA, USA has produced a drug in tobacco leaves called ZMapp, which has been used to combat the 2014 Ebola virus outbreak in Africa [1]. Several plant-derived drugs have been commercialized as research and diagnostic reagents (such as tobacco derived aprotinin and rice derived lysozyme from Sigma-Aldrich Company (St. Louis, MO, USA) or received USDA approval as a vaccine additive for use in poultry (Dow Agro Sciences, Indianapolis, IN, USA) [1], the current review mainly focuses on PMF in relation to human pharmaceutical applications. The drug is produced in carrot cells using a large bioreactor under very stringent conditions This process is different from production of other PMF products, which generally use entire leaves, fruits, seeds, or whole plants to produce the recombinant pharmaceutical. The cost of PMF-derived products is only 0.1% of mammalian cell culture systems and 2%–10% of microbial systems

Challenges
PMF Products for Use as Topical Applications and Health Supplements
Transient Expression Platform
Moss Culture
Algal Bioreactors
Seed-Based Platforms
Downstream Processing
Findings
Conclusions
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