Saskatchewan Looks Past AgBiotech Roots

Located in Canada’s heartland, Saskatchewan is recognized for its agricultural biotechnology and livestock genomics. With about half of Saskatchewan’s land devoted to agriculture, it’s not surprising that the province’s biotechnology companies have agricultural roots. Phenomenome Discoveries, which specializes in metabolomics profiling, is an exception.

Neuroscientist Dayan Goodenowe, Ph.D., developed mass spectrometry methods to perform comprehensive analyses of metabolites in biological samples. The patented process and supporting bioinformatics form the metabolomics biomarker platform at Phenomenome Discoveries, which Dr. Goodenowe and John Hyshka cofounded in Saskatoon in 2000.

The company’s first product is a serum-based biomarker test for colon cancer. Canadian physicians are testing the screening method to see how it compares to colonoscopy results. Patient samples are sent to Phenomenome, where the high-throughput test is performed. “We want to position it as a precolonoscopy screening tool to select patients who are at high risk for colon cancer,” says Alix Hayden, director of business development.

The goal is to better allocate expensive colonoscopy resources and select patients who will benefit most from the invasive procedure. Other biomarker screening tests for ovarian cancer, Alzheimer’s disease, autism, and multiple sclerosis are in the company’s pipeline.

Phenomenome offers contract biomarker screening services for pharmaceutical, nutrition, and agricultural clients. “Our technology detects small molecules in an unbiased manner in any complex biological mixture,” according to Hayden. Additionally, the biomarker platform uncovers the biochemical processes underlying a disease, which are used to design targeted small molecule drugs. “It’s biomarker-driven therapeutic development,” Hayden explains. The first candidates will move into clinical trials within 18 months.

In the second quarter of 2008, Phenomenome plans to open Phreedom Sante, a personal metabolic health monitoring clinic that will perform biomarker testing for the public. The biomarkers such as oxidative stress and lipid profiles are linked to chronic conditions and can be detected up to 10 years before clinical symptoms occur.

Clients will be given advice about appropriate medications or life-style changes like diet and exercise to improve their health. The same biomarkers can then be used to monitor whether drugs or lifestyle changes successfully reduce disease risks. “It’s a novel direct-to-consumer approach to motivate people to take preventive action,” Hayden remarks.

Saponin was formed to commercialize natural chemicals stored in seeds of Saponaria vaccaria. This wild prairie carnation makes large amounts of saponins and other bioproducts. Saponins are gentle, nonionic detergents found in shampoos and products for laundering delicate fabrics. Their natural foaming action makes them key ingredients in beer, soft drinks, and fire extinguishers.

In the last five years, medical applications of saponins have been discovered. Saponins structurally resemble steroids and interact with cell membranes. “We are studying some of the potential medical uses of saponins, specifically immunostimulatory properties for use in vaccines,” says Paul Arnison, Ph.D., CSO and cofounder. The strong immune response to saponins provides an opportunity to prepare low-cost adjuvants on a large scale for animal healthcare applications. A longer-term goal is to develop human vaccine adjuvants.

Additionally, the plant’s seeds are rich in starch with commercial value. The starch particles, which are extremely tiny, have unique texture properties that are desired by the cosmetic industry.

“Industrial markets for saponins and starch are already established,” says Dr. Arnison. The company is developing Saponaria as a crop for western Canada, followed by sales of the plant’s starch and saponins.

Poultry Vaccines

Founded in 2001, Guardian Biotechnologies focuses on developing better vaccines for the poultry industry. The company is perfecting a vaccine for Coccidiosis, a disease caused by a group of intracellular protozoan parasites that produce intestinal lesions and weight loss that costs poultry producers $1.5 billion worldwide. The parasites have rapidly developed resistance to drugs used since the 1950s.

“The current vaccines are live vaccines made by feeding chickens small amounts of a parasite,” points out Jim MacPherson, Ph.D., CSO. The parasite enters the intestines, replicates, and is excreted in feces. Then the live parasite is collected from feces and cleaned in a very time consuming and expensive process. “Our approach is molecular and based on very specific immunizing antigens,” says Dr. MacPherson. The laboratory-made vaccine contains no live parasites, which should reduce manufacturing costs.

Guardian’s vaccine can be fed to chickens or delivered in ovo; i.e., injected into developing eggs at day 18 just before chickens hatch at day 21. Poultry growers prefer the in ovo method, because all eggs are currently vaccinated this way against Marek’s disease.

“We can apply our vaccine to this system,” Dr. MacPherson says. The company is conducting dosing studies of its Coccidiosis vaccine. Another vaccine for Newcastle virus, which destroyed 3.5 million birds in California in 2003 and cost $104 million to contain, is in the pipeline.

Oilseeds for Biofuels

Agrisoma Biosciences, founded in 2002, develops crops genetically engineered for biofuels. The company’s plant-transformation system allows up to 20 genes to be inserted into plants to modify oils used to make biodiesel and other biofuels. “Oil-based plants like canola are the starting point for biodiesel,” explains molecular biologist Steve Fabijanski, Ph.D., CEO. “We have developed the means to significantly change oil composition and yields to address the growing need for renewable energy.”

In standard gene-insertion methods, one or two genes are added randomly to plants, and researchers pick the best outcomes. In contrast, Agrisoma scientists identified a specific region within plant chromosomes where they could insert a suite of genes that act together, such as those that control oilseed production. The insertion site, or heterochromatic DNA, located in the pericentric region of acrocentric chromosomes, is highly stable and supports gene expression.

When Agrisoma researchers use their method to insert genes that modify oilseed production, yields increase 40% to 50%. When the same genes are inserted using standard methods, though, yields rise only 5%. The company also created technology to load new genes into this region to achieve further productivity gains.

Agrisoma is engineering canola and other oilseeds to increase monounsaturated oils and long chain fatty acids, which are optimal for biodiesel production. They are also engineering soybeans as a source of biofuel oils. This same expression system could be used to make healthier food oils such as products with high omega-3 fats or to manufacture vaccines in plants. For the short-term, “the company is focused on biofuels and the renewable energy market,” says Dr. Fabijanski.