H2020 NEWCOTIANA Project: Development of multipurpose Nicotiana crops for molecular agriculture using new plant breeding techniques

Plant biotechnology plays an emerging role in the production of small-molecule medicines, biologics (vaccines and therapeutics), and diagnostic reagents. It offers a scalable and low-cost alternative to traditional manufacturing platforms based on microbial and animal cells. Furthermore, it can address the challenges caused by drug distribution and storage, especially in regions of the world with incomplete production chains. New varieties of tobacco plants for drug production Tobacco plants are highly valued as plant biofactories due to their potential as valuable sources of high-value compounds. However, because it is associated with the manufacture of smoking products, tobacco cultivation is in continuous decline in Europe. The EU-funded project Newcotiana (Opens in a new window).

The project aimed to change this perception by developing competitive Nicotiana varieties that can be used for smokeless products, creating a production platform suitable for the EU bioeconomy and bringing sustainability to a traditional crop. The consortium worked with two plant species: Nicotiana tabacum, the commonly cultivated tobacco, and Nicotiana benthamiana, an Australian wild tobacco. To fully exploit the potential of these species as biofactories, scientists had to incorporate specific traits associated with stability, sustainability, and the yield of high-value compounds. Tools to engineer new plant traits Since it was not possible to generate these traits through traditional crop improvement methods, the consortium developed tools to facilitate the accelerated breeding of plant biofactories. “For centuries, we have bred our plants using traditional breeding techniques to produce more and better food, or to resist pathogens, but not to improve biofactories for medicines,” highlights project coordinator Diego Orzáez.

New breeding techniques, including genome editing, improved plants for use in biofactories in record time. The researchers engineered tobacco plants that do not flower in the field but conserve energy to increase their biomass. Furthermore, they engineered these plants to avoid unwanted glycosylation or to reduce protease activity, two traits involved in the quality and functionality of the final protein products obtained from the plant. In several cases, the plants were modified to contain a combination of these special traits. Applications of Engineered Plants In the case of the cultivated tobacco species N. tabacum, the consortium enriched the plant's composition with value-added compounds for pharmaceutical use. One of these compounds was squalene (opens in a new window), a substance currently obtained mainly from unsustainable sources (sharks) and used as an adjuvant in many vaccine formulations. The researchers also produced Anatabine(opens in a new window), a nicotine-related molecule with anti-inflammatory effects, which is being investigated as a possible treatment for various autoimmune diseases.

The engineering of N. benthamiana was slightly different, as this plant was already used by industry to produce recombinant proteins used in cosmetics and pharmaceuticals. The Newcotiana partners shared the N. benthamiana genome sequence to assist the teams in the discovery of new biopharmaceuticals. A Zero-Waste Biorefinery Process Along with efforts to improve the market value of these varieties and perhaps enrich them with additional high-end molecules, the researchers established a pilot zero-waste biorefinery procedure. "The goal is to create a crop and an associated industry that is at least as profitable as smoking tobacco cultivation was," Orzáez emphasizes. "To achieve this, EU legislation must be more flexible and support the engineering of industrial crops."