Looking to move into the genetic-disease testing market, TessArae this week announced a deal with GeneDx to develop and launch array-based tools for detecting the genetic mutations responsible for several diseases.
Under the terms of the deal, Potomac Falls, Va.-based TessArae will provide Gaithersburg, Md.-based GeneDx with arrays and software to detect all known mutations in eight genes of the RAS/MAPK pathway that are associated with Noonan Syndrome, a genetic disorder that causes abnormal development of multiple parts of the body.
The two firms are also developing a test for Periodic Fever Syndromes that GeneDx said it will commercialize in coming weeks. According to the Cleveland Clinic, Periodic Fever Syndromes are diseases that cause episodic fevers in patients and do not have an infectious cause.
For TessArae, which specializes in developing pathogen-detection arrays, the deal with GeneDx is the first of its kind. The company said this week that it intends to pursue more opportunities in the genetic disease-testing arena.
TessArae CEO and President Klaus Schäfer said in a statement that the "human genetic disease-testing market represents a new opportunity" for the firm. He said TessArae's resequencing microarray platform is "ideally positioned, from both a cost and time-to-result perspective, between conventional and next-gen DNA sequencing technologies" to serve the market, and will "generate significant revenue as the genetic testing market grows."
"This market was definitely not part of our original business strategy, but based on our expertise in resequencing microarrays, we decided to pursue the initial opportunity with GeneDx," said Matthew Lorence, vice president of market and sales at TessArae.
Lorence told BioArray News this week that though the Noonan and Periodic Fever Syndromes project is exclusive with GeneDx, the firm is already working with an "international company and a US university to develop new arrays and assays for other disorders."
One partner is "developing a cancer array, looking at a broad number of oncogenes, and the other is looking at recessive diseases," Lorence said. He declined to discuss those projects in greater detail.
TessArae has sought to provide its customers with array-based pathogen detection tools since its inception in 2005. The firm's TessArray Resequencing Pathogen Microarray platform enables the detection and identification of viral, bacterial, and fungal pathogens, from clinical, environmental, and product samples, according to the firm.
TessArae currently sells the RPM-Flu Kit for detection and definitive identification of respiratory pathogens, the RPM-TEI Kit for tropical and emerging infections, and the RPM-HFV Kit for the whole-genome resequencing of hemorrhagic fever viruses. All of TessArae's chips are manufactured by Affymetrix.
According to Lorence, it was Affy that referred GeneDx to TessArae. TessArae then developed the array and assay to detect the mutations in the genes underlying the disorders.
The "key component" of the package is a new algorithm to call diploid sequence from the arrays, as opposed to haploid sequence from microbes, Lorence said. "This turned out to be difficult since many genetic disease mutations are single-base changes, requiring the ability to read two different nucleotides, with very high accuracy, at a single-base position."
TessArae's algorithm reads the wild-type sequence from the reference tiles on the array at a greater than 99 percent call rate, and uses an array design strategy to ensure complete detection of targeted mutations, Lorence said.
He added that TessArae envisions its technology being used by genetic testing labs to detect mutations or disorders that they currently detect by Sanger sequencing.
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According to Lorence, GeneDx is now regularly using the array and assay in its diagnostic work with patient samples, and finds that the "time-to-result and overall cost significantly improves" versus conventional Sanger sequencing. "Rather than sequencing every individual exon in each of the eight genes involved in Noonan Syndrome by Sanger sequencing to identify one or two mutations, they can screen for all targeted mutations simultaneously on a single array in 24 hours," he said. "Putative positive mutations are confirmed by Sanger sequencing for accuracy."
John Compton, GeneDx's CEO and scientific director, told BioArray News this week that the firm has been offering Noonan Syndrome testing for years, and previously used capillary sequencing to look at four genes for mutations related to the disease, typically handling between 70 and 100 cases per month.
He said that by using array technology, the company can now look at eight related genes at the same time. "The situation when you have a disorder with overlapping genes is that it gets expensive and time-consuming to analyze all of those genes to be thorough," Compton said. "Doing them one after the other takes a long time and there are built-in cost factors that lead to a pretty hefty price," he said. To sequence the set of four core genes related to Noonan Syndrome could cost customers around $3,000 and take 15 to 20 weeks, Compton said. By using the Affy platform, the firm can look at four more related genes and turn around an analysis in 5 weeks for around $1,500.
Compton said that GeneDx has plans to put additional tests onto its Affy GeneChip system in the future. "There are many appropriate situations where this technology would be advantageous," Compton said. "One could use this technology as a screening method. If an individual has mutations that are detectable, you can get at them more cheaply and effectively, right away," he said. "Those for whom you did not detect a mutation would proceed to be analyzed by another method."
At the same time, Compton noted that the company will not be switching all its tests over to the array platform. He said that arrays have "several technology limitations," one being that "you can only detect sequences that you have designed into the system." Using capillary sequencing, for instance, he said it is possible to "see any possible change." Compton said that arrays at present "will not detect sequence changes that are not designed onto the chip itself.
"In many disorders, insertions and deletions into genes have significant frequency and those changes can cause disease," Compton said. "In a disorder where that's more frequent, [array] technology will miss all of those," he added.
Compton said that GeneDx had evaluated using Affy arrays years ago and passed on what is still considered a new technology. Now, the company sees the platform as "appropriate" for its needs. Earlier this year, GeneDx also began offering gene-sequence analysis for genes associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and long QT syndrome, using Illumina's second-generation sequencing platform, the Genome Analyzer.
"We will continue to use new technology where it provides advantageous qualities, including lower cost and less time," Compton said.