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By Malorye A. Branca

June 12, 2002 | Dramatic declines of 60 to 80 percent in the price of genotyping combined with the introduction of higher throughput platforms are suddenly making pharmacogenomic studies more affordable and practical.

“The price of genotyping for research is very quickly coming down,” says Jeff Olson, senior director of molecular biology at Cambridge, MA-based Variagenics Inc., which does a large volume of genotyping. “If you are not at 50 cents or lower, you are very quickly being pushed out of the game.”

Genotyping’s high cost has long been one of the major obstacles to pharmacogenomic research. Individual studies can require looking for hundreds of thousands of SNPs (single nucleotide polymorphisms) in many hundreds of patients. Such studies reveal highly accurate markers of disease and pave the way to patient-tailored therapy.

Until recently, the cost to identify a single SNP was generally about $1 per genotype.  But over the past few months several companies have aggressively cut prices. San Diego-based Illumina Inc. started the trend last October when it launched a new genotyping service at a significantly lower price point. “We take quite a bit of pride in having entered the market at about 20 to 35 cents per genotype,” says John Stuelpnagel, vice president of business development at Illumina.

Shortly after that, Applied Biosystems Group (ABI)  cut the price of the popular Taqman reagents by about half. ABI declined to provide specific pricing, but Taqman users say the cost dropped to about 40 cents per genotype. “One of our major goals is to bring down the cost of Taqman-based projects down and make them more competitive,” says David Dailey, ABI’s genomic assays business application marketing manager.

In late April, Orchid Biosciences Inc. launched its SNPstream UHT platform. After the initial $250,000 price of the platform, the cost of genotyping with SNPstream can fall to less than 35 cents per genotype, including PCR reagents, according to Orchid spokeswoman Barbara Lindheim. Cost per genotype with this system decreases as more samples are run simultaneously.

Prices are still too high for genome-wide scans that must look at hundreds of thousands of SNPs in as many patients. For those kinds of studies to be practical, the price must shrink to about 1 cent per SNP. Nevertheless, current prices make smaller studies far more feasible.

“You can look at a few SNPs, across a couple hundred candidate genes, in less than a hundred patients and find strong correlations between diseases and drug response,” says Richard Judson, senior vice president of informatics at Genaissance Pharmaceuticals Inc. “For complex diseases like heart disease and diabetes though, you need 500 or 1,000 patients to do it right.”

Several factors affect genotyping costs, among them the upfront cost of instrumentation, whether PCR is required (and if so, how much), and whether the system is available as a service or a product. Sequenom’s mass spectrometry approach, for example, requires expensive instrumentation but uses unpurified oligonucleotides (oligos), which are substantially less expensive than the purified and labeled oligos. With some systems, the cost per genotype only goes down appreciably for large volumes of tests. Finally, genotyping services tend to cost more than buying reagents off-the-shelf and doing the work yourself.

Technology improvement -- largely, the ability to process more samples more quickly -- is one of the forces driving the genotyping cost reductions.

Illumina’s system is particularly well suited to multiplexing, or doing many tests at once. “Our technology gives us a competitive advantage starting at 100 SNPs per sample, and at least 100 samples,” says Illumina’s Stuelpnagel. Costs continue to fall as the volume scales up, he says. Both the new Orchid platform and Third Wave Technologies Inc.'s Invader are also very high throughput, allowing as many as half a million genotypes to be performed in one day.

Besides cost and throughput, researchers look for accuracy, ease of use, and flexibility. Orchid and ABI have made technical advances to standardize their assays, making them much easier to use. Accuracy, always important, has become an even higher priority as more groups try to take their tests to the clinic.

Taqman and Third Wave’s Invader technology are considered two of the strongest competitors for the clinic right now, but most other suppliers also have their eyes on that market. “Our technology is clearly a discovery tool today,” says Steulpnagel, “but I think that eventually we will be able to address the clinic, too.”

For reprints and/or copyright permission, please contact Angela Parsons, 781.972.5467.