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Facing Growing Competition, Invitrogen Debuts Its First Single-Species miRNA Chip

BOSTON — Invitrogen this week unveiled version 3.0 of its NCode miRNA microarray, an all-human tool that the company hopes will distinguish it in an increasingly competitive market for microRNA-profiling research tools.
Invitrogen, which began selling NCode arrays in November 2005, also plans to create an miRNA microarray exclusively for murine research — the company said that the mouse is the second-most popular species for its miRNA array customers — and launch it within two or three months.
Version 3.0 of the human chip, which is not the only all-human miRNA array on the market, contains all 541 known human miRNAs in the Sanger Institute’s miRBase database, which was last updated in December, plus 350 novel miRNA sequences that Invitrogen licensed last October from Natural Selection, a San Diego computational technology firm (see BAN 10/9/2007).
According to Christopher Adams, R&D manager for epigenetics at Invitrogen, the company decided to offer single-species arrays to miRNA researchers to distinguish itself in the market from increasing numbers of competitors that offer multi-species arrays, as well as to serve a customer base that is primarily interested in studying human systems.
“We had six different species on our first NCode chip, but we realized that human is the most important organism,” he told BioArray News at Cambridge Healthtech Institute’s microRNA in Human Disease and Development conference, held here this week. “We will continue to offer a multi-species array, but we have heard from a lot of customers that they didn’t need all of that content.”
He said that between 80 percent and 90 percent of Invitrogen’s customers “are looking at human miRNAs, and the bulk of research is focused on humans, so it made sense to offer the market a human miRNA chip.”
Invitrogen also believes that the content it licensed from Natural Selection will give it an edge in what Adams calls a “rapidly growing market.” Natural Selection’s 350 miRNA sequences were identified using Illumina’s next-generation sequencing instrument, the Genome Analyzer. Adams said that “the new content was added to help researchers discover more sequences related to cancer, heart disease, and embryonic stem-cell differentiation.”
To be sure, these 350 sequences have yet to be added to the miRBase catalog and officially recognized as microRNAs, but Adams said that they “fit all the criteria in order to be called a putative miRNA sequence in terms of size and reproducibility.”
Invitrogen said it plans to combine Natural Selection’s mouse miRNA sequences with the latest miRBase mouse miRNA sequences to create a mouse-specific miRNA microarray that will be ready for the market this spring or early summer.
Data Crunch
Adams said that there is “an even distribution among customers in all sectors of research” for NCode chips, from core facilities to academics to pharmaceutical companies and biotechs.
One challenge many users face, however, is data analysis. As Adams explained, because the content of miRNA chips is low compared with whole-genome SNP-genotyping arrays sold by firms like Affymetrix and Illumina, many researchers who are unfamiliar with array technology are less intimidated by using NCode as a discovery platform.
“The amount of content [on these chips] has opened the door for the average Joe to do array experiments,” Adams said. “MicroRNA profiling in general is an array platform that is amenable to every lab out there. So this has taken the mystery out of the whole business and reduced the fear of the unknown, because there are only a few thousand features on each array.”
Invitrogen has developed a free, online software-analysis tool called NCode Profiler that can be saved to a user’s desktop to meet the analysis needs of its less experienced customer base. The software enables researchers to design array templates that support sample-to-sample comparison within the experiment. For each tissue on the array, the software determines pairwise differential expression and generates test statistics, fold change, and p-value, according to the firm’s website.

“When we started out three years ago, there were two or three companies selling miRNA arrays. Now there are 10.”

Additionally, the software calculates the ranking of each miRNA marker with respect to other markers within the tissue. Normalized data can be exported to visualization software for clustering and heat-map analysis. Adams described Profiler as “miRNA analysis made easy” and said that bioinformatics will continue to be another area where firms that sell miRNA arrays will look to distinguish themselves.
Staying ahead of other firms, though, has become increasingly difficult. In 2005, increases in the number of miRNA-related scientific publications prompted firms such as Exiqon, CombiMatrix, and Invitrogen to debut miRNA expression-profiling chips within months of each other. And over the past two years, other firms have entered the market, including Agilent Technologies, Febit, and Illumina, all of which debuted miRNA chips last year, as well as companies like Asuragen and LC Sciences, which specialize in miRNA array-based services.
All of the firms differ in regards to the pricing and content of their chips. Agilent, for example, offers a human miRNA array, while Exiqon’s miRCURY arrays contain human, rat, and mouse miRNAs as well as viruses related to these species. LC Sciences, which uses a microfluidic chip rather than a spotted array in its service, argues that all of its arrays are technically custom arrays, and therefore the content is always tailored to meet the research interests of the customer (see BAN 3/4/2008).
“The market and our customer base are growing rapidly, but so is the competition,” said Adams. “When we started out three years ago, there were three companies selling miRNA arrays. Now there are 10,” he said. “It has become more competitive, and everyone has to update their content and improve upon what they offer to stay ahead of the competition.”
Adams said that Invitrogen will not be raising the list price of its version 3.0 chips, which currently cost around $220, despite the increased content and related features. The company is also touting its chips as open platform. While it recommends BioMicro Systems’ MAUI hybridization system for use with NCode, it said its chips are compatible with most instrumentation sold in the market today, including systems sold by rivals like Agilent.
Deep Sequencers
An elephant in the room is next-generation sequencing technology. Several presenters at this week’s conference have shown miRNA data generated on high-throughput sequencers like Illumina’s Genome Analyzer and Applied Biosystems’ SOLiD System. The question is whether sequencing will eventually displace arrays in the miRNA research field, or instead fuel array usage by discovering additional well-characterized miRNA sequences. Adams predicts the latter.
“Deep sequencing technology will advance this field rapidly,” he said. “Everyone believes that those machines will revolutionize this research. But still there will be a need for arrays, because not everyone wants a billion data points. The average lab worldwide is not ready to jump into that kind of technology.”
Adams cited the fact that Invitrogen is now selling novel miRNA sequences discovered using Illumina’s next-gen sequencing platform as evidence that the two technologies will complement each other going forward.
“Deep sequencing feeds into the array market,” he said. “What arrays can do is take an important sequence and allow people to look at that content in an easier and more affordable manner.”

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