Farmacule grows proteins in tobacco

Graeme O'Neill, Australian Biotechnology News
http://www.biotechnews.com.au/index.php?id=33469691

22 November 2005

Brisbane agbiotech Farmacule BioIndustries has taken a step towards the era of molecular 'pharming' by producing vitronectin, a high-value human protein used in medical research, in genetically modified tobacco plants.

Also known as S-protein or serum spreading factor, vitronectin is a component of the extracellular matrix, the scaffolding that organizes living cells into tissues.

After developing techniques to extract and purify the protein from tobacco tissues, Farmacule researchers have now confirmed that performs identically to commercial vitronectin purified from human and animal serum in a 'gold standard' cellular migration assay.

Vitronectin is widely used to coat cell-culture plates, because of its ability to promote attachment and proliferation of mammalian cells.

Vitronectin has other important functions in the body that make it of interest to researchers working in thrombosis, inflammation and wound repair, cancer, infection and biomimetics.

It has a positive role in regulating blood clotting and vascular repair after injury. It limits narrowing of blood vessels and premature clotting after arterial injuries.

As a promoter of cell adhesion and migration, vitronectin has recently been implicated in the metastasis of malignant tumour cells -- it could become a novel target for anti-cancer therapies that would inhibit its activity, reducing the viability of cancerous cells.

Vitronectin is also suspected of promoting respiratory infections by the pathogenic microbe Pseudomonas aeruginosa, a perennial problem in patients with cystic fibrosis.

The protein also promotes the attachment of cells to biomaterials such as titanium orthopaedic implants and intraocular lenses used to treat cataracts.

Farmacule business development manager Hayley Brotherton said that vitronectin derived from animal serum currently costs between US$1.7 million (AUD$2.3 million) and $5 million per gram. The high cost reflects the cost of purifying the protein, and the cost of meeting quality-assurance standards.

She said Farmacule anticipated it could produce the protein in plants much more cheaply. From its biosecure glasshouse at Queensland University of Technology, containing several dozen tobacco plants, it could produce around 1 gram per month - more than enough to supply the total world demand.

Farmacule has inserted the vitronectin transgene into elite, high-biomass tobacco lines from Australia's major source of tobacco germplasm -- the selected lines are very low in nicotine, and other metabolically active substances, and free of tobacco and human pathogens.

Farmacule's proprietary INPACT technology allows the company to use a number of different gene promoters to selectively express human or mammalian transgenes in leaf, stem or root tissues in plants.

The beauty of the transgenic tobacco expression system, Brotherton said, is that commercial quantities of high-value proteins can be produced in a single, biosecure glasshouse, avoiding the need to meet the complex regulatory requirements involved in growing transgenic crops on farms.

She said Farmacule planned to focus on these high value proteins, but would eventually move to broadacre transgenic crops like sugarcane or tobacco to produce lower-value proteins such as industrial enzymes, or bioplastics.