On the southern outskirts of the city of Owensboro in Kentucky, USA, there is a square and nondescript building. Inside, rows and rows of small plants grow under artificial lights.
It is a new generation biotech company: a molecular farm . Others are flourishing across the United States and elsewhere and are growing vaccines . This means that if we find a working coronavirus vaccine, its products could be used by households around the world.
The basic idea of molecular agriculture is to genetically modify plants so that, together with all their usual biochemicals, their cells produce biomolecules that are useful to us . It is not a new idea.
This field began in 1989, when researchers arranged tobacco plants to produce a proof-of-concept for antibodies. There was a lot of uproar in the next decade. One of the first ideas was that this could produce edible medicines . Bananas, for example, express the vaccines in their cells . Molecular agriculture seemed like a world-changing idea, capable of providing medicines easily and cheaply to billions of people.
One of the reasons it didn’t take off, says Professor Julian Ma of the University of London in the UK, is that it can be difficult to control the dose with edible vaccines: “How can you prevent someone from eating 20 bananas because Do you think it’s good? There was a time when everyone got really excited. And then they realized that, oh no, it’s not really going to be that simple. “
Living things have biomechanics that use a nucleic acid code as an instruction manual to build proteins. Molecular agriculture takes over this machinery and makes it use synthetic instructions to make new proteins. But bacteria and other mammalian cells, such as the Chinese hamster ovary (CHO) cell, can do this too. In fact, CHO cells are the most common way to grow proteins. Cultured proteins are used primarily as drugs, to treat conditions such as diabetes and blood clotting problems. Farming methods are more expensive and time consuming than molecular farming, but the processes involved are well established and validated for safety. Molecular agriculture has yet to get there. But it is starting to catch up.
Plants
A few years ago, Professor Ma conducted a proof-of-concept study to show that an antibody could be produced in plants and isolated from them using simple separation techniques. The resulting proteins could be just as pure and therefore safe for medical use.
Another useful factor is the emergence of a genetic modification technology called transient expression. It is a technique that consists of making cells temporarily express some DNA. In plants it is easy to do so. It involves dipping them in a special solution and then letting them grow. This means that, in some cases, scientists studying plants can go from genetically modifying them to making them express new proteins in two weeks or even less.
Molecular culture facilities are becoming more and more common. The Owensboro farm is owned by Kentucky BioProcessing, a long-standing company that helped produce ZMapp antibodies to help treat Ebola during the 2015 outbreak. Another large facility is under construction in Quebec, Canada. And Brazil has also announced its intention to build one, says Professor Ma. “I see this as a small advance. It is the first in the southern hemisphere. “
It is in this context that Dr. Diego Orzáez, from the Institute of Molecular and Cellular Plant Biology in Valencia, is directing the Newcotiana project. Dr. Orzáez says that although there are many large farms, no one has gone to great lengths to raise the plants they use to improve their productivity. He and his team are working on just that.
They are working with two plants that are closely related. The first is Nicotiana bentamiana , a fragile dwarf cousin of the tobacco plant, which is the species grown on most commercial molecular farms because it is so easy to genetically modify. The second is Nicotiana tabacum , the largest and most resistant plant commercially grown for tobacco. The plan is to optimize both.
Tobacco
There is a special reason why Dr. Orzáez wants to work with Nicotiana tabacum . He says there are communities across Europe that have traditionally grown tobacco for use in cigarettes, but face a certain stigma for doing so. Some of these communities are located in the relatively humid area of La Vera, in the Extremadura region. According to Dr. Orzáez, many of these communities are keen to switch to tobacco growing, which could be put to better use, providing drugs instead of tobacco.
Admittedly, there is a snag in the plan because plants that have been genetically modified cannot be legally grown outdoors in the EU due to the rules on genetically modified organisms. However, Dr. Orzáez says he hopes to convince authorities that this must change. This is because the plants in your project, although officially classified as GMOs, have been produced by gene editing and do not contain genes from other organisms like most GMOs.
In the meantime, he says he has some encouraging results. You have produced a non-flowering cultivar of Nicotiana tabacum , which means that it cannot propagate seeds or pollen and therefore should be safe to grow outside. Orzáez has generated another separate cultivar that produces an anti-inflammatory compound. The next step is to combine them into a single plant line. It also has improved versions of Nicotiana bentamiana in field tests.
In all of Dr. Orzáez’s work, proteins are expressed in the leaves of the plant. But there are reasons why it would be useful to express them in other parts of this one.
“If you wanted to store a vaccine, for example, the seeds would be perfect,” said Professor Ma. “They are natural protein storage organs and are incredibly stable. You could produce a barn of seeds and keep it almost forever. “
Professor Ma coordinates a project called Pharma-Factory, which is developing new cultivation platforms, so that proteins can be expressed not only in leaves but also in seeds, roots and algae. The project includes five small companies and the plan is to have several therapeutic proteins, including an HIV-neutralizing antibody , developed to the point of commercialization.
Coronavirus
And what about the coronavirus? Several large molecular culture companies are already working on vaccines. For example, Quebec-based Medicago has made plants produce proteins that can be assembled into a virus-like particle, which is essentially the shell of the SARS-CoV-2 virus protein with nothing inside. . The company says the results of the mouse tests initiated antibody production and it expects to begin phase 1 clinical trials in humans this summer.
For their part, the Newcotiana team published the Nicotiana benthamiana genome sequence before being ready for formal publication in an academic journal. “Many companies and academics will benefit from knowing as much as possible about the plants themselves through this genome,” said Dr. Orzáez.
Dr. Orzáez also says that his team has dedicated itself to working on the coronavirus, modifying some of its plants to produce the spike protein of the SARS-CoV-2 virus . This spike protein is an important reagent in serological tests that determine whether a person has developed antibodies to COVID-19 . In plants it can be produced quickly and easily in places where the supply of protein is low. The team has yet to work to make sure the proteins they produce are validated for safety, but if they are, molecular agriculture could be one way to help mass testing.
The fundamental attractions of molecular agriculture have not changed since the 1980s. It is cheap, it is safe, and it can be easily and quickly scaled up. As the coronavirus pandemic continues and a race to develop working vaccines rages on, the latter fact can prove extremely attractive, especially in poor parts of the world.
ArtÃculo original
This article was originally published in Horizon, the EU Research and Innovation Magazine
