Abstract

In 2012 scientists funded by the United States Defense Advanced Research Projects Agency (DARPA) produced 10 million doses of influenza vaccine in tobacco in a milestone deadline of one month. Recently the experimental antibody cocktail Zmapp™, also produced in tobacco, has shown promise as an emergency intervention therapeutic against Ebola virus. These two examples showcase how collaborative efforts between government, private industry and academia are applying plant biotechnology to combat pathogenic agents. Opportunities now exist repurposing tobacco expression systems for exciting new applications in synthetic biology, biofuels production and industrial enzyme production. As plant-produced biotherapeutics become more mainstream, government funding agencies need to be cognizant of the idea that many plant-produced biologicals are often safer, cheaper, and just as efficacious as traditionally used expression systems.

Highlights

  • For almost two decades, plants of the family Solanaceae and Brassicaceae have been attractive for use in expressing a range of biotherapeutics, the most notable products being antibodies and vaccine-stimulating antigens

  • The use of green plants, tobacco (Nicotiana benthamiana and Nicotiana tabacum), to express products to combat infectious bacterial and viral agents has been the subject of hundreds of primary publications and numerous review articles [1,2]

  • The DNA plasmid constructs engineered by researchers to be transferred from bacteria into plants have historically incorporated or built upon genetic elements of tobacco mosaic virus (TMV) or other plant viruses that replicate in tobacco leaves, further justifying the use of tobacco as a plant host for expression of these target biotherapeutics

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Summary

Introduction

Plants of the family Solanaceae and Brassicaceae have been attractive for use in expressing a range of biotherapeutics, the most notable products being antibodies and vaccine-stimulating antigens. To produce biotherapeutics in tobacco, Agrobacterium tumefaciens containing a cloned recombinant DNA plasmid are introduced into the plant tissue, but in some instances plant viruses can alternatively be engineered. Through a process referred to as agroinfiltration plant-produced hormones, cytokinins, auxin and opines interact with virulence components encoded by the bacteria that allow bacterial transfer and expression of the cloned gene within the tobacco leaf. The DNA plasmid constructs engineered by researchers to be transferred from bacteria into plants have historically incorporated or built upon genetic elements of tobacco mosaic virus (TMV) or other plant viruses that replicate in tobacco leaves, further justifying the use of tobacco as a plant host for expression of these target biotherapeutics.

Production of Biotherapeutics in Tobacco
Why Use Tobacco to Express Vaccines?
Future Directions and Opportunities
Perceptions Related to Tobacco Biotechnology
Conclusions
Methods
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