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Genetic engineering - back to the future

A tiny plant, built like a "Russian doll" and used as food for ducks, may be the next thing in the biotechnology industry. A group of Israeli researchers managed to turn it into a reliable and cheap machine for the production of genetically modified proteins

"The Institute" magazine

The water lens
The water lens

A non-glow aquatic plant, which is a favorite food of ducks and other waterfowl, may play an important role in the pharmaceutical industry. It floats and spreads over freshwater and still water surfaces in different parts of the world, and it can be a suitable habitat for protein drugs such as insulin, or vaccine components and antibodies whose sales potential reach billions of dollars a year. This is the water lentil plant, better known by the nickname "duck grass", which indicates the great affection of winged people who see it as a tasty and nutritious food.

The water lentil grows at an extremely fast rate, and it contains a large amount of proteins. In Southeast Asia it is used as a basic food for fish and various farm animals. Its ability to absorb large amounts of substances from water is used in the USA to clean sewage. But the real business opportunity for this versatile plant awaits in the pharmaceutical industry.

To produce proteins that are used as drugs, pharmaceutical companies usually use biological systems that "know" how to produce proteins. To harness them to the craft, the scientists insert a gene encoding the desired protein, for example human insulin, into a living system - a bacterium, a mammal cell or a plant. At this stage they allow the system to grow and produce the protein, which is isolated at the end of the process.

But all the existing systems for producing proteins that are used as medicines - like everything else in life - also have shortcomings. The bacteria cannot always produce proteins with a suitable structure for the human body. Mammalian cells are indeed able to produce (in culture) proteins suitable for humans, but in order to be able to do so they "require" sterile conditions, the cost of which can reach hundreds of millions of dollars. And these two systems are difficult to maintain and operate efficiently on an industrial scale.

Looking for solutions in plants

In search of a cheaper and larger system, the pharmaceutical industry is turning to genetically modified plants, such as corn and tobacco, which are not infected with various viruses and parasites, which can damage mammalian cells. But these transgenic plants face resistance from those who fear the unknown effects of transgenic plants on the environment.

This is exactly where the benefits of the water lentil plant come into play. This tiny plant excels at the fastest growing rate in the plant world. It can double its biomass in less than 48 hours. It grows beautifully in artificial light, in simple water containing some minerals, with its only carbon source being the carbon dioxide in the air.

The summary of these features means that it can be grown inside a building, with the help of cheap and relatively simple equipment, and without fear of impact on the environment. The fact that it is used as food for farm animals raises the possibility that a genetically engineered water lens, which will contain immune proteins, could in the future be used for a vaccine that will be given as food for flocks, poultry, fish, and possibly even humans. This method of administering drugs and vaccines orally may save the expensive process of producing the proteins, and make the drugs cheaper.

But if this is indeed the case, why doesn't the pharmaceutical industry take full advantage of the water lens? The problem is in the structure of the tiny plant, which resembles a Russian doll, which contains a second doll, which contains a third doll, and so on. Similar to this structure, the growth pocket of the water lentil contains the leaves of the next generations of the plant, each of which carries several future generations. This unusual structure makes it difficult to directly engineer the water lentil: genes that are inserted into the leaves of the plant fail to be passed on to the leaves of the following generations, so that within a generation or two, the engineered vegetable "forgets the Talmud", returns to its original natural version, and ceases to produce the desired protein.

Dismantle the Russian doll

This is precisely where Prof. Meir Edelman and the members of his research group in the Department of Plant Sciences at the Weizmann Institute of Science entered the picture. In an effort that lasted about ten years, they managed to dismantle the "Russian doll" of the water lentil, and turn the plant into a reliable and readily available protein production machine. At first, Prof. Edelman used the water lens in his research in the field of photosynthesis, the process by which plants produce energy-rich substances with the help of solar radiation. Only later did it become clear to him that he had found a gold mine for the biotechnology industry.

To "tame" the unruly water lentil, Prof. Edelman and the members of his research group use a cocktail of hormones and other substances, which return the cells of the plant's growth area to their embryonic stage, before they differentiate and "specialize" in performing defined roles in the adult plant. In this embryonic state they form a shapeless green mass that can be reliably engineered. After inserting the desired genes into them, the scientists launch the clump cells back into the future: they reprogram them to restore their ability to differentiate and become a mature plant.

All the cells of this new plant include the gene that encodes the desired protein, so that all future generations of the plant will continue to produce it. Together with partners from the industry, Prof. Edelman developed a new variety of water lentil called "giant". This variety is twice as large as a normal water lentil plant, has double the amount of DNA, and produces correspondingly more proteins. The researchers hope that "giant" will help turn the delicate water lens into a huge industry.

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