Editing tobacco for drugs rather than cigs

newcotiana tobacco plantsSmoking is an addiction; tobacco, however, is a model plant full of virtues. Docile to biotech interventions, metabolically exuberant, able to churn out plenty of proteins. Now it has attracted 7.2 million euros through an EU research project aiming to harvest biopharmaceuticals by harnessing the power of photosynthesis and new plant breeding techniques.

It is called Newcotiana, and it involves 19 academic and industrial partners from 9 countries, coordinated by Spain. “We will produce small molecules. Carotenoids with a protective function for the eye and pyridine alkaloids useful for palliative purposes for Alzheimer and multiple sclerosis,” says Giovanni Giuliano from the Enea-Casaccia Research Centre in Italy. Other groups in the consortium will manufacture proteins such as monoclonal antibodies and vaccine antigens.

The first step is to optimize the techniques for use in common tobacco (Nicotiana tabacum) and in a wild relative (Nicotiana benthamiana). Then researchers must regulate glycosylation and proteolysis in scaffold plants, to “humanize” molecules and increase proteins production. Finally, the metabolic pathway for nicotine must be re-directed towards substances of interest. “We can do it by using CRISPR the classic way, knocking out two to three genes,” says Giuliano. The CRISPR enzyme (Cas9) can be introduced together with its guide RNA, without transferring foreign DNA. “Resulting plants are not transgenic and should not be subject to the same restrictions as GMOs,” he adds. If European legislation takes into account the opinion of scientists, as well as the EU Court of Justice ruling expected later this year, life will be much easier for edited plants. “The EU Commission is interested in Newcotiana and another EU-funded CRISPR project, precisely to inform its decison-making process,” says Giuliano. In three years time edited N. benthamiana will grow indoors, while open field trials with N. tabacum will debut in Spain which is the most GM-friendly country in Europe. Molecular farming might offer tobacco growers the chance to revive their activity creating new healthy uses. Tobacco’s potential was already proven in the past by producing the ingredient for a hepatitis B vaccine in Cuba, the malaria drug artemisinin in Germany, the Ebola vaccine Zmapp in the US. “Plants advantages for the manufacture of high value molecules are huge, regarding production rate per biomass unit and costs. Yeast cells may be ten times more expensive as  biofactories”, calculates Giuliano.

Tobacco’s genome is complex (allopolyploid indeed, because it derives from the hybridization of N. sylvestris and N. tomentosiformis), so CRISPR’s ability to modify multiple genes simultaneously is particularly valuable. Graft breeding is another approach to be experimented by Max Planck researchers involved in the Newcotian project, with the hope of expanding the range of compounds produced.




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