Imagine a world in which any protein, either naturally occurring or designed by man, could be produced safely, inexpensively and in almost unlimited quantities using only simple nutrients, water and sunlight. This could one day become reality as we learn to harness the power of plants for the production of recombinant proteins on an agricultural scale. Molecular farming in plants has already proven to be a successful way of producing a range of technical proteins. The first plant-derived recombinant pharmaceutical proteins are now approaching commercial approval, and many more are expected to follow.

A functional comparison was made between a monoclonal secretory antibody generated in transgenic plants and its parent murine IgG antibody.The affinity constants of both antibodies for a Streptococcus mutans adhesion protein were similar. However the secretory antibody had a higher functional affinity due to its dimeric structure. In the human oral cavity, the secretory antibody survived for up to three days, compared with one day for the IgG antibody. The plant secretory antibody afforded specific protection in humans against oral streptococcal colonization for at least four months. We demonstrate that transgenic plants can be used to produce high affinity, monoclonal secretory antibodies that can prevent specific microbial colonization in humans. These findings could be extended to the immunotherapeutic prevention of other mucosal infections in humans and animals.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for an ongoing human pandemic . There is a massive international effort underway to develop diagnostic reagents, vaccines, and antiviral drugs in a bid to slow down the spread of the disease and save lives. One part of that international effort involves the research community working with plants, bringing researchers from all over the world together with commercial enterprises to achieve the rapid supply of protein antigens and antibodies for diagnostic kits, and scalable production systems for the emergency manufacturing of vaccines and antiviral drugs. Here, we look at some of the ways in which plants can and are being used in the fight against COVID-19. COVID-19: How Can Plant Biotechnology Help?An outbreak of potentially lethal coronavirus (SARS-CoV-2; see Glossary) in Wuhan, China, in December 2019, has created a pandemic (COVID-19) that has provoked governments across the world to introduce emergency containment and control measures. The aim of these measures is to delay the spread of infection, thus reducing the acute pressure on hospital beds, frontline medical staff, and resources. Slowing down the rate of infection and thereby reducing the total number of acute cases at any one time can help to prevent the collapse of national healthcare systems. These tactics also give researchers more time to develop effective testing assays to identify carriers, treatments that reduce the severity of symptoms and resolve infections more quickly, and vaccine candidates to protect the unexposed segment of the population. Researchers working on the applications of plants can have a key role during this critical time by using their knowledge and infrastructure as a means to develop and produce new diagnostics and therapeutics. Indeed, plants may offer the only platform that can be used to manufacture such reagents at scale in a timeframe of weeks, compared with months or even years for cellbased systems. Here, we look at three areas where plants could make major contributions: diagnostic reagents to identify infected and recovered individuals, vaccines to prevent infection, and antivirals to treat symptoms.

The genes encoding the heavy and light chains of a murine monoclonal antibody (mAb Guy's 13) have been cloned and expressed in Nicotiana tabacum. Transgenic plants have been regenerated that secrete full-length Guy's 13 antibody. By manipulation of the heavy chain gene sequence, constant region domains from an immunoglobulin alpha heavy chain have been introduced, and plants secreting Guy's 13 mAb with chimeric gamma/alpha heavy chains have also been produced. For each plant antibody, light and heavy chains have been detected by Western blot analysis and the fidelity of assembly confirmed by demonstrating that the antibody is fully functional, by antigen binding studies. Furthermore, the plant antibodies retained the ability to aggregate streptococci, which confirms that the bivalent antigen-binding capacity of the full length antibodies is intact. The results demonstrate that IgA as well as IgG class antibodies can be assembled correctly in tobacco plants and suggest that transgenic plants may be suitable for high-level expression of more complex genetically engineered immunoglobulin molecules. Since mAb Guy's 13 prevents streptococcal colonization in humans, transgenic plant technology may have therapeutic applications.

Plant molecular pharming has emerged as a niche technology for the manufacture of pharmaceutical products indicated for chronic and infectious diseases, particularly for products that do not fit into the current industry-favored model of fermenter-based production campaigns. In this review, we explore the areas where molecular pharming can make the greatest impact, including the production of pharmaceuticals that have novel glycan structures or that cannot be produced efficiently in microbes or mammalian cells because they are insoluble or toxic. We also explore the market dynamics that encourage the use of molecular pharming, particularly for pharmaceuticals that are required in small amounts (such as personalized medicines) or large amounts (on a multi-ton scale, such as blood products and microbicides) and those that are needed in response to emergency situations (pandemics and bioterrorism). The impact of molecular pharming will increase as the platforms become standardized and optimized through adoption of good manufacturing practice (GMP) standards for clinical development, offering a new opportunity to produce inexpensive medicines in regional markets that are typically excluded under current business models.

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