28 Oktober 2004

Wild tomato hairs, the world’s first protein factory

The wild tomato could yet become the world’s first factory for therapeutic proteins, thanks to an alliance between plant biotechnology pioneer Evogene and Compugen (Nasdaq: CGEN).

Evogene will be evaluating the feasibility of using plants to produce proteins that Compugen, a bioinformatics and drug discovery company, believes could have therapeutic potential.

The ambitious startup will be evaluating the production feasibility using its proprietary Plant Made Pharmaceutical platform. There are three potential proteins in the plant-production pipeline, it added.

Compugen has unique technology to locate proteins that could have therapeutic or diagnostic potential. Under the agreement, it will supply Evogene with the genetic coding of three therapeutic protein candidates that it discovered and tested using its predictive models and discovery engines.

Evogene will study the feasibility of producing these therapeutic protein candidates using its proprietary plant-based protein production platform – the humble wild tomato.

Mass-production of proteins

It is all but impossible to mass-produce synthetic proteins using conventional chemical methods. Proteins are extremely complex chains of amino acid molecules that can only function in certain biological and chemical conditions. Evogene is essentially creating a science of producing life chemicals using life forms.

The process of building a cell-based production lines typically takes some four years and costs hundreds of millions of dollars. Various studies estimate that by the year 2006, there will be a grave shortage of protein production, and that the market by 2010 will reach $125 billion. About half these proteins will be produced using plant cells.

About 40 companies are working on the technique. Evogene says most of the potential competition has low production capacity, of a few tens of grams of protein a year, while it will be producing kilograms a year.

The uniqueness of Evogene’s platform is that it is based on utilizing the existing machinery of a specific plant tissue that naturally produces a very high concentration of a native protein, and the plant tissue allows easy harvesting and extraction of the protein. An additional advantage is that the plant platform has been designed to be grown under containment conditions.

“The world is waiting for a plant platform that assures high-concentration production and easy extraction,” says Dr Gil Ronen, manager of plant production at Evogene.

Hairy tomatoes

Why the wild tomato, by the way? Well, it isn’t the fruit itself that will produce the proteins, it’s the ‘hairs’ on its leaves and stalks, called trichomes.

Some of the trichomes on the wild tomato have bulbous ends. When a bug steps on them, the head bursts and releases a glue causing the insect to stick to the hair. The trapped insect is thus prevented from harming the plant.

That bio-glue consists of two substances, one of which is a natural protein. Since the bulbous ends explode wit hair-triggers, so to speak, if the tomato can be persuaded to produce the target protein in its hairs, collecting the product becomes relatively easy.

Ronen calculates that a quarter-acre of greenhouse tomato crops can produce 1- kilos of protein a year. Even if the company produces only a tenth of that amount, it will be beating rival companies, he says.

Another advantage to using a plant platform is that animal cells can bear viruses harmful to man, whereas plant cells lack that propensity. But plant cells have a downside, in that their proteins attract sugar molecules whose influence remains to be elucidated.

Companies active in protein production from plants have raised more than $150 million to date. Most of the money went to the top five or six companies. Evogene itself has raised $7.5 million since being spun off from Compugen in 2002, and it is in the process of raising up to $5 million more.

Breakthroughs in recombinant DNA

The advent of recombinant DNA technology has resulted in numerous breakthrough biopharmaceutical products in areas such as cancer, autoimmune disease and cardiovascular disease, Compugen explains.

More than ninety approvals or new indications for biopharmaceuticals have been granted by the FDA since 2000, and more than 1,000 protein-based therapeutics are at various stages of development, with 200-300 in late stage clinical trials.

Currently, mammalian cell culture is the dominant method for the manufacture of biological products, but mammalian cell culture production is complex and costly. It is characterized by long process development and scale-up times (3-5 years), high and rigid capital requirements (between a quarter-billion dollars to $500 million) and elevated operating costs. Using genetically modified plants for human protein production is an area of great interest in the industry. Several companies are competing to create platforms for this purpose.

Production of human proteins in plants potentially has substantial economic and qualitative benefits, including reduced health risks from pathogen contamination (such as prions responsible for mad-cow disease) and mammalian viruses (such as HIV and Hepatitis B), lower capital requirements and operating costs, faster scale up and much greater production flexibility. In addition to providing these potential advantages of protein production in plants, Evogenes proprietary platform addresses two of the major bottlenecks inherent in most plant protein production platforms now in development by others: harvesting and extraction of the target protein and its subsequent purification.

Initiated in 1999 as a division of Compugen, Evogene was established as a separate company in 2002 by Compugen and founders Drs. Hagai Karchi and Rafi Meissner.

Source: The Marker.com Oct. 25, 2004.

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