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Bio-Rad Jumps Into RNAi Field With IDT Pact; Takes Aim at BCW Rivals in Growing Market

Bio-Rad Laboratories last week jumped into the RNAi field through a collaboration with Integrated DNA Technologies and is hoping to carve out a niche in a fast-growing market that is crowded by several BCW Index rivals.

The alliance signals Bio-Rad's intent to be a major competitor in the RNAi field, in which it will compete with several other BCW Index firms including Invitrogen, Qiagen, Sigma-Aldrich, Applied Biosystems, and Fisher Scientific. However, Bio-Rad is collaborating on a different RNAi technology than that covered by patents licensed from MIT to the others for research purposes.

"Certainly, we've been interested in entering this sector," Brad Crutchfield, vice president and group manager of life science for Bio-Rad, told BioCommerce Week. The IDT partnership is "consistent with us supporting the entire customer workflow of gene expression analysis," he said.

Under the agreement, Bio-Rad will pair its transfection and analytical instruments with IDT's siRNA design and synthesis expertise and deliver to customers validated Dicer-substrate 27-mer small interfering RNA duplexes. Bio-Rad said that it also would experimentally validate IDT's siRNA duplexes in live cells.

The partners said that they also intend to develop a series of control kits for use with IDT's TriFECTa Dicer-substrate RNAi kits and Bio-Rad's validated siRNA duplexes.

"An important step in the customer workflow is getting these siRNAs into the cell, and we have a product to do that," said Crutchfield. "This really does fit well together — and of course the natural step that goes with this is a gene expression assay using real-time PCR."

The technology at the heart of the pact was developed by John Rossi at City of Hope's Beckman Research Institute and was exclusively licensed a year ago to IDT for research and functional genomics applications. It uses synthetic RNA duplexes between 25 and 30 nucleotides long to trigger RNAi silencing.

According to a paper by Rossi et al. published in the February 2005 issue of Nature Biotechnology, initial work with the technology indicated that 27-nucleotide long RNA duplexes could be up to 100 times more effective at silencing genes than conventional 21 nucleotide-long siRNAs — which is the technology covered by the so-called Tuschl patents MIT licensed to Bio-Rad's rivals.

Crutchfield said he didn't want to "overstate" the potential effectiveness of the technology over 21-mer siRNAs. "Technically, I think that in our hands a well validated 27-mer is very, very effective," he said.

"I think customer expectations are to get success and move on," said Crutchfield. "It's no longer cool that you can just silence or at least inhibit a gene. They want essentially a kit kind of approach to being able to silence specific genes. So, we really felt this gave us an opportunity to provide that."

A Different Path

In collaborating with IDT and City of Hope, Bio-Rad has chosen to go down a different path than its rivals, who all hold licenses to the Tuschl patents. Those patents cover technology that is jointly owned by MIT, the Whitehead Institute, the Max Planck Institute, and the University of Massachusetts, but MIT is authorized to act on behalf of the other institutions in licensing out the technology. MIT has licensed the technology to Dharmacon, Ambion, Qiagen, and Proligo.

"It's no longer cool that you can just silence or at least inhibit a gene. They want essentially a kit kind of approach to being able to silence specific genes. So, we really felt this gave us an opportunity to provide that."

MIT's licensing strategy, combined with the desire of many tool providers to get into the RNAi research space, led to a wave of consolidation over the past couple of years. Qiagen got the ball rolling with its April 2002 acquisition of Xeragon, which was followed by Invitrogen's November 2003 purchase of Sequitur, Fisher Scientific's April 2004 acquisition of Dharmacon, Sigma-Aldrich's February 2005 acquisition of Proligo (see BioCommerce Week 2/24/2005), and ABI's acquisition of Ambion in March this year (see BioCommerce Week 1/4/2006).

Invitrogen was the only one of these players not to have purchased a firm with a license to the MIT patents. Like Bio-Rad, Invitrogen chose to develop and sell a different RNAi technology — the Stealth RNAi compounds produced by Sequitur, which are essentially siRNAs around 27-mer in length that have been modified so that they will not trigger a cellular interferon response.

Indeed, intellectual property issues were one of the reasons Bio-Rad decided to partner with IDT, but certainly not the only reason.

"Partly, it's that the freedom to operate has been limited by the patents out of MIT," said Crutchfield. "We've also had a longstanding relationship with the City of Hope, and so we were able to see the power of these things."

IDT "can obviously produce these siRNA duplexes for gene silencing, but the real challenge with these is to have them optimized and validated," said Crutchfield. "Really it was an opportunity for us to have a source, because making these [is] not that easy.

"So, we have the freedom to operate with the intellectual property and we have the source of these sequence-specific siRNA complexes," he said.

Bio-Rad also has a separate agreement with City of Hope, said Crutchfield, adding, "It's kind of a three-way partnership."

Bio-Rad is the only commercial entity to license the 27-mer technology from IDT on the research side, he said, while City of Hope has a separate licensing strategy for therapeutic applications.

Some market estimates have placed the total in vitro RNAi market at $500 million by the end of 2007, but Crutchfield thinks Bio-Rad will be competing for a smaller amount of money. "We think it's a very large market," he said. "But really we see this as a market … of $100 million-plus in the next few years."

Among its competitors in the RNAi field, Crutchfield singled out ABI as "really the only other company that brings a total-solution approach to it. Most of the other companies are bringing individual products or kits," he said.

"In the end, the customers don't care in terms of the individual products," said Crutchfield. "They're trying to answer questions and get data and move on. A lot of people are adopting this technology as part of their research, not because they're particularly interested in the technology but in the outcome."

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