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Invitrogen Expands NCode Array Line with Non-Coding RNA Chips for Human, Mouse

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Invitrogen last week announced that it has expanded its NCode microarray product line, adding high-density microarrays that profile non-coding and messenger RNAs in human and mouse.
 
An Invitrogen official said that adding non-coding RNA-profiling chips to its catalog is a “natural progression” for the company, which has sought to carve out a place for itself in a microarray market dominated by Affymetrix, Agilent Technologies, and Illumina.
 
The new chips include a kit for studying human non-coding RNA and one for mouse. The human arrays target 17,000 ncRNAs and include 22,000 coding RNA probes from the RefSeq database and other collections, which enables users to analyze ncRNA expression with associated protein-coding genes. Meantime, the mouse arrays contain probes for over 10,000 ncRNAs and include roughly 25,000 coding RNA probes.
 
Both kits are manufactured by Agilent Technologies in a multiplex format, with each slide containing two 105,000-feature arrays. According to Invitrogen, one slide costs $785.
 
Invitrogen, which jumped into the array market in 2005 with the launch of its NCode multi-species miRNA chip, “was an early participant in the miRNA field and realized the potential in the non-coding RNA field several years ago,” Wendy Price, director of product management at Invitrogen, told BioArray News this week. “Invitrogen's plans in this field were always to start with miRNAs and then expand into the larger field of non-coding RNAs.”
 
To reach that goal, in 2005 Invitrogen began working with John Mattick’s lab at the Institute for Molecular Bioscience at the University of Queensland in Brisbane, Australia. Mattick’s lab has published numerous papers describing ncRNAs and believes that ncRNA profiling is relevant to researchers studying cancer, neurological disorders, and stem-cell development.
 
In January Invitrogen obtained an exclusive license to proprietary content discovered at Mattick’s IMB lab.
 
Mattick’s group “added the coding content to enable researchers to profile both coding and non-coding [RNA] on the same array,” said Price. “The goal was to cover as much of the coding genome as space on the array would allow, in addition to the validated non-coding content.”
 
She added that because the non-coding content on each array comprises transcripts larger than 200 bases, researchers could use them to complement, rather than replace, the company’s miRNA chips.
 
The ncRNA arrays “do not duplicate content that is already covered on the NCode miRNA array, so the arrays complement each other perfectly,” said Price. “The non-coding RNA chips round out the complete workflow Invitrogen has made available for profiling, which now includes array content and controls, labeling and qRT-PCR validation.”
The Oz Connection
 
In March, three years after launching its multi-species miRNA chip, Invitrogen updated the portfolio with a human-focused third version of the chip (see BAN 11/16/2005, BAN 3/11/2008).
 
This week, Price said the ncRNA field is developing “very rapidly,” but declined to offer a market size. According to a PubMed search of “non-coding RNA,” 300 papers have been published on the topic so far this year, compared to slightly over 200 in 2007. The Mattick lab alone has published 60 papers on the topic since 2002.
 
Marcel Dinger, a postdoc in Mattick’s group who helped develop the new NCode arrays, told BioArray News this week that Invitrogen’s platform will give the lab the “opportunity to look at more than 10,000 long ncRNAs in mouse or in human in many different developmental systems.”
 

“If you're using an array to look at all protein-coding genes, why wouldn't you cover your bases and look at what the non-coding RNAs are doing as well?”

“Together with our ever-improving annotations of long ncRNAs, these results will integrate with other genome-wide analyses to inform candidates for further functional studies,” Dinger said. “For many of these systems, we work closely with collaborators that are expert in relevant systems, where we can help guide them to the best candidates and provide some insight into what experiments might be effective in showing their function.”
 
Dinger also said he believes the demand for such research tools is increasing. “The pace that this field has been changing over recent years, particularly in the past few months, has been astounding,” Dinger said. “We see new papers in all the top journals on an almost weekly basis describing more functions and mechanisms of long non-coding RNAs.”
 
According to Dinger, while the field is “clearly still in the very early stages of understanding the importance of these RNAs,” there is a “rapidly growing acceptance now that studying these RNAs will be crucial in understanding the biology of complex eukaryotes.”
 
Dinger also anticipates that the new arrays will see “widespread” use. “After all, given the extensive precedents for function, if you're using an array to look at all protein-coding genes, why wouldn't you cover your bases and look at what the non-coding RNAs are doing as well?” he said.
 
The connection between the Mattick lab and Invitrogen goes back three years, when the group released RNAdb, a catalog of mammalian ncRNAs, many of which were uncharacterized.
 
Although ncRNAs at the time were “generally regarded as transcriptional artifact or ‘junk’, the Mattick lab was working under the hypothesis that the majority of these transcripts were functional,” Dinger said. “Invitrogen saw the potential for new products that would be necessary to explore this emerging field of research.
 
“Due to the large number of non-coding RNAs, a microarray was the obvious first tool to develop to get a better insight into how these transcripts were behaving in different systems,” he added.
 
At first, the Mattick group largely relied on arrays spotted in-house to perform non-coding RNA-expression profiling. Dinger said that the group also has used LC Sciences’ custom arrays to look at small RNAs, and chips from Combimatrix and Roche NimbleGen to survey long non-coding RNAs.
 
He said that the Mattick group is working on siRNA knockdown of long ncRNAs, and has also used fluorescent in situ hybridization to look at their subcellular localization. The lab also plans to run second-generation sequencing projects on ABI’s SOLiD platform.
 
OEM Option
 
One chief difference between Invitrogen’s microRNA arrays and its new set of non-coding RNA chips is the manufacturer. While Invitrogen makes its miRNA arrays in-house, Price said that Invitrogen had to work with an original equipment manufacturer for the new chips because the “amount of non-coding content we had available required a higher density than we currently offered.”
 
The chips are manufactured at Agilent’s facility in Santa Clara, Calif., using the company’s inkjet SurePrint technology. Chris Grimley, Agilent’s senior marketing director of genomics, told BioArray News this week that the NCode OEM deal represents the “first time” that Agilent is manufacturing arrays for Invitrogen on an OEM basis.
 
Agilent has had a number of high-profile OEM deals recently. Last month, Oxford Gene Technology began selling a line of universal prokaryotic arrays for a number of applications manufactured by Agilent (see BAN 10/7/2008). And in September, Millipore said that Agilent will act as an OEM for a line of arrays for chromatin immunoprecipitation-on-chip studies it plans to launch next year (see BAN 9/9/2008).
 
“The OEM business is definitely part of our strategy to drive microarray volume,” Grimley said. “We feel that Agilent’s strengths in this segment are the same that we offer other users of microarrays in emerging applications,” such as the flexibility to “place any probe at any location on an array,” the “ability to produce multiple formats,” and the “ability to synthesize high-quality probes.”

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