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SuperArray Picks PCR over Microarrays As It Enters miRNA-Expression Market

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SuperArray, which has made a name for itself by selling chips in spotted-array and microtiter-plate formats, this month became the latest firm to enter the microRNA expression-profiling tools market.
 
But rather than going head to head against firms like Invitrogen or Exiqon that sell spotted miRNA microarrays, SuperArray has decided to sell miRNA content via PCR performed in microtiter plates, an older format that the company said is superior to microarrays because of its “dynamic range and the sensitivity of RT-PCR.”
 
As an entrée into the market, SuperArray has launched four different miRNA PCR arrays: one to analyze all known human miRNAs, another for miRNAs linked to cancer, a third devoted to miRNAs associated with cell differentiation and development, and one for the most abundant miRNAs that it will market to customers “who are new to the miRNA world,” according to a company official.
 
Jeffrey Hung, the firm’s director of marketing, told BioArray News last week that SuperArray was enticed into the growing miRNA expression profiling market by because it is an “absolutely new area for studying gene regulation.” SuperArray’s initial miRNA array customers have been “normal life scientists and normal biomedical researchers who are studying specific biological phenomena and activities,” Hung said.
 
For these “normal” researchers who have been fueling the rise in the number of platforms on the market, the technology options are increasingly varied. There are already several firms, including Invitrogen, Exiqon, Agilent Technologies, and Febit, that offer miRNA expression profiling on spotted microarrays. Then there are companies like Illumina and Applied Biosystems that market their next-generation sequencing instruments for use in miRNA-profiling experiments.
 
Because of SuperArray’s background, the firm could have produced an miRNA expression-profiling product using either spotted arrays or PCR arrays. Hung said that there were several reasons for why the firm decided to choose PCR over a traditional microarray format.
 
“We deliberated quite a lot internally and we chose to focus on the RT-PCR format for a couple of reasons,” said Hung. “One is obvious: the wide dynamic range of 9-log versus 2-log magnitude,” he said. “That certainly presents a much wider opportunity for researchers to identify low-abundance miRNA changes.”
 
SuperArray also “didn’t see much sacrifice in terms of the throughput of the RT-PCR because of the limited numbers of miRNA,” said Hung. “In humans right now there [are] between 600 and 700, so even for a 384-well plate it takes two plates at most” to cover all known human miRNAs.
 
Only the firm’s human miRNA PCR array is currently available in a 384-well format. The cell-differentiation array, the miRNA finder chip, and the cancer array, which contains miRNAs thought to be the most relevant and abundant in tumor- and oncogenesis, are available in a 96-well plate format.
 

“When you do a trade-off analysis we see a much higher performance on the dynamic range and the sensitivity so we decided to go with the RT-PCR.”

SuperArray, based in Frederick, Md., is not the only firm selling PCR arrays instead of spotted arrays for miRNA expression-profiling research. ABI, which also has access to spotted microarray technology, last July launched its TaqMan Array Human MicroRNA Panel, essentially a high-throughput RT-PCR assay performed in a 384-well-plate format (see BAN 7/24/2008).
 
Iain Russell, product manager for ABI’s TaqMan microRNA assays, told BioArray News at the time that TaqMan chemistry coupled with low sample input requirements offers researchers more potential to profile miRNA than microarray tools sold by rivals.
 
“In cases where researchers are looking to detect and quantify genes that are expressed at low levels, such as miRNA genes, the TaqMan arrays offer the sensitivity to detect genes at very low copy numbers that would otherwise be invisible to genome survey technologies, such as microarrays,” he said.
 
‘Not High-Throughput Enough’?
 
One factor that has enabled firms like SuperArray and ABI to introduce products into this market has been the low number of known miRNAs. SuperArray’s Hung said that he does not expect the final number of known miRNAs to be much more than the number of human miRNAs that have already been discovered. “I believe it will stay in that ballpark,” he said.
 
In contrast, Søren Møller, chief scientific officer and vice president of R&D at Exiqon, told BioArray News this week that the increasing number of miRNAs made spotted miRNA arrays, like those sold by his firm, a more attractive platform for miRNA-expression profiling.
 
“The content of [the Wellcome Trust Sanger Institute’s] miRbase is rapidly expanding,” Møller said. “Today there are more than 700 human miRNAs in miRbase, and more microRNAs are being discovered. Therefore, users will have to run several microtiter plates, even 384-well [plates], to do a complete profiling of a sample.” By comparison, he said, a single Exiqon array “profiles all miRNAs.”
 
He said he is also skeptical of the value of cancer miRNA arrays being sold by some of Exiqon’s competitors, including SuperArray. “Cancer-relevant miRNAs are not yet defined in all cases, and therefore selection of relevant sub-sets is difficult, and a certain selection may overlook important miRNAs,” he said.
 
In general, the firm believes that “PCR arrays are not high-throughput enough due to requirements for automation” for widespread use — though Exiqon has launched its own RT-PCR-based miRNA-profiling product line based on its internally developed locked nucleic-acid technology.
 
Other companies that sell to the miRNA expression-profiling market, like Houston, Texas-based LC Sciences, have also introduced miRNA qPCR services for data validation (see BAN 3/4/2008).
 
Møller said that in a market where customers are expected to choose between spotted arrays, PCR arrays, and sequencing instruments, “all technologies have their optimal application space.” For Exiqon, he said, PCR is more suited for validation rather than general expression profiling. With that in mind, Møller said that Exiqon is currently mulling adding catalog qPCR arrays to its portfolio.