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Sigma-Aldrich Taps Rosetta Inpharmatics to Add Bioinformatics Chops to Growing RNAi Business


Sigma-Aldrich this week said that it had exclusively licensed siRNA design algorithms from Merck subsidiary Rosetta Inpharmatics to bolster its RNAi technology portfolio.

The Rosetta agreement is the latest in a series of licensing deals that Sigma has signed in the RNAi sector in the wake of its acquisition of Proligo last year. Since then, the firm has signed IP agreements with RNAi patent-holders Alnylam, Benitec, and Oxford BioMedica, and has also entered into an agreement with the non-profit RNAi Consortium to make and sell short-hairpin RNA libraries developed under that effort.

Now the company is betting on bioinformatics to give it an additional edge in the increasingly competitive RNAi sector, which includes rivals Invitrogen, Qiagen Fisher subsidiary Dharmacon, and Applied Biosystems subsidiary Ambion.

Algorithms for designing effective siRNAs are "absolutely key" to the use of RNAi as a research tool, Keith Jolliff, director of strategic marketing for Sigma's biotechnology business unit, told BioInform this week.

"In order to use [RNAi] as a research tool, you have to have specificity," Jolliff said, "and the way you obtain specificity is by integrating a bunch of design parameters that are the characteristics of RNA interference" into an algorithm.

"The vendor that has the dominant design platform has a significant advantage in the industry."

Sigma-Aldrich currently uses siRNA-design software that it inherited from Proligo. "While it's adequate, it's not state of the art, so in order to provide a best-in-class product, we felt we needed to go out and partner with somebody with world-class capabilities like Rosetta," Jolliff said.

Doug Bassett, executive director of informatics at Merck Research Laboratories, said that Rosetta has been developing siRNA-design algorithms for several years to support Merck's internal RNAi-screening programs.

The effort, led by Peter Linsley, vice president of research at Rosetta Inpharmatics, has focused primarily on optimizing siRNA design to reduce off-target effects. The Rosetta developers have also refined their design methodology to achieve "maximal knockdown," particularly for low-expressed genes, Bassett said.

Sigma's Jolliff cited Rosetta's focus on off-target effects as a key advantage over competing design methods. "They have included all of the most recent design parameters so that it's very good at eliminating cross-reactivity with other targets," he said. "It greatly decreases the likelihood of triggering an interferon response, an antiviral response, and it has much less cross-reactivity in non-specific manners with other genes."

He said that the Rosetta design algorithm can also discriminate between the RNAi pathway and the microRNA pathway, which is an important distinction in ensuring that the siRNA knocks down the appropriate gene.

Bassett said that Rosetta has compared its siRNA-design method with competing approaches, but declined to provide specific benchmark data. "We feel we have a very strong approach," he said.

Rosetta felt that it was "the right time" to make the technology available to the broader marketplace, Bassett said. Sigma, Merck, and Rosetta had an ongoing relationship, which led to the licensing agreement, he said.

Although Rosetta Inpharmatics is the parent company of bioinformatics software provider Rosetta Biosoftware, Bassett said that it didn't make sense to commercialize the siRNA-design technology in a shrink-wrapped software format. "The market is for the siRNAs themselves" — not the design software, he said. While the chemistry behind the siRNAs is important, Bassett said that the quality of the sequence design can be crucial. "The vendor that has the dominant design platform has a significant advantage in the industry," he said.

Online siRNA Design Services from Leading RNAi Vendors

Sigma-Aldrich's Proligo siRNA Design service:

Invitrogen's BLOCK-iT RNAi Designer:

Ambion's siRNA Target Finder:

Dharmacon's siDESIGN Center:

Qiagen's siRNA Design Tool:

Jolliff said that Sigma-Aldrich will use the Rosetta technology to design whole-genome siRNA libraries for both human and mouse — an effort that should take about a year.

In the meantime, a pared-down version of the algorithm will be available via the company's website by September that will enable researchers to design their own siRNAs — a strategy employed by Sigma's competitors in the RNAi market (see box).

"A product the customer gets by designing their own will still be superior, but not to the level that it would be with the pre-designed libraries that we'll be designing," Jolliff said. "The point here is that hopefully within a year we will have a design for every single gene, so then it won't be necessary for individual researchers to design their own."

— Bernadette Toner ([email protected])

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