A lot of know-how, a tobacco plant and a dash of genetic engineering: that’s all a team of Australian researchers needed to produce a possible treatment for multiple sclerosis.
Everyone knows today that cigarettes are a scourge that has a disastrous impact on public health. But tobacco plants also have fascinating properties that could make them very interesting in medicine, and more specifically in pharmacology. This is the subject of work by a duo of researchers from the University of Queensland; in their latest publication, they proved that Nicotiana benthamianaa strain of tobacco originating in Australia could be used as bio-factory to produce all kinds of drugs in large scale.
David Craik and Mark Jackson, specialists in molecular biology, started from a simple observation: modern pharmaceutical production is based on an excessively expensive model. The production of these complex compounds is very expensive. In addition, it involves large quantities of chemicals, a significant part of which tends to be wasted, according to the authors.
To overcome this problem, they have already been working for ten years on another approach: using the extremely powerful tools with which nature has gradually endowed plants as they evolve. The idea is to hijack the cellular machinery plants to achieve a new efficient, economical and sustainable drug production system.
DNA loops against multiple sclerosis
Some plant species, including Nicotiana benthamiana, are able to produce loops of amino acids (the building blocks that make up the proteins around which life is built). We then speak of cyclotides.
The structure of these cyclotides makes them particularly stable. They can pass through the entire digestive system without being damaged, which gives them very interesting properties in medicine. This makes it possible in particular to integrate them with drugs administered orally.
Several studies have already suggested that these compounds could help treat serious diseases such as multiple sclerosis. Today, there is still no really satisfactory therapeutic solution to treat this very debilitating autoimmune disease which affects the central nervous system.
Despite great progress over the past twenty years, with the rise in power of targeted immunotherapies, the results are still quite mixed and are often accompanied by serious side effects. It is therefore urgent to find alternative methods to improve the daily lives of these patients.
Reprogramming plants through molecular engineering
Based on these observations, Craik and Jackson unsheathed their arsenal of bioengineering. Their goal: to use Nicotiana benthamiana to design a treatment that is practical, economical and effective.
They began by identifying the genes that allow the plant to synthesize these famous cyclotides. They then called on a laboratory specializing in the production of vectors. In this context, this term refers to small pieces of artificial DNA with a very precise sequence that can be grafted into the genetic heritage of a living being using molecular engineering tools, such as Crispr-Cas9.
This allows researchers to modify certain physiological functions at their leisure. In other words, it amounts to reprogramming the cellular machinery of tobacco so that it produces not its usual peptides, but a chemically different version.
In this case, the target is [T20K] kB1. It is a cyclotide which is currently the subject of a clinical trial, because it presents a significant potential in the fight against multiple sclerosis.
The researchers amplified all of this material using the polymerase chain reaction, or PCR. This technique makes it possible to clone a DNA sequence on a large scale very quickly. During the Covid-19 pandemic, it was used daily to amplify samples collected from patients, in order to maximize the chances of detecting viral particles. Here, the objective was to produce large quantities of genetically modified material without having to insert this famous vector thousands of times.
This modified gene has been integrated into Agrobacterium tumefaciens, a small bacterium highly prized by molecular geneticists. She has the ability tointroduce a DNA fragment directly into the genome of a plant cell. Researchers therefore use it regularly to carry out various manipulations based on transgenesis.
Just before flowering, the team inoculated the tobacco plants with this bacterium. This made it possible to transfer this famous modified gene to growing plants. Five days later, they proceeded to harvest before freezing the material produced to reduce it to powder.
After additional purification steps and centrifugation, they obtained a significant amount of the [T20K] kB1 mentioned above. In other words, they could “reschedule” the plant so that it produces a substance likely to improve the management of multiple sclerosis.
A vast and very concrete potential
The other advantage is that in theory it is quite easy to increase the scale of production. No need to build an extremely expensive state-of-the-art factory. Just grow more plants using only light, water and a cocktail of nutrients.
The most interesting thing is that this method is not reserved for multiple sclerosis. In theory, it is enough to be able to construct the necessary genetic vector and find a suitable host. From there, we can imagine producing a whole bunch of different therapeutic molecules. All while avoiding the constraints of heavy industry.
” Thanks to modern molecular biology, we can teach plants to produce the molecules that interest us Craik said in a statement. ” Our work offers a platform for the cultivation of other treatments against pain, cancer or obesity. »
The text of the study is available here.