National Editor

About three years after entering an antisense-based agreement with Bristol-Myers Squibb Co., Sequitur Inc. said the companies are taking the deal into another year and will include the latter's capabilities with RNA interference, or RNAi.

Specifically, privately held Sequitur will perform biological screening assays and provide Bristol-Myers with RNAi for use in target validation studies as part of what was described as the companies' "multiyear, multimillion-dollar" collaboration.

"Sequitur was not working in RNAi when the agreement was signed [in January 2001]," said Tod Woolf, Sequitur's president. "We got into RNAi about a year and a half ago, and now we're providing RNAi compounds to a large number of pharmaceutical companies."

RNAi, which Woolf noted might be thought of as a form of antisense, "silences" gene expression by deploying small interfering RNA, called siRNA, to degrade messenger RNA, which is the link between DNA and proteins.

Until the advent of RNAi, which works on double-stranded RNA, scientists believed only the single-strand RNA (as is used in conventional antisense) had an impact on post-transcriptional gene expression.

"It's a phenomenon," Woolf said of RNAi. "About a year ago, it started going wild. Its low toxicity has led us to incorporate it into our research."

The original deal with Bristol-Myers was for Sequitur to provide access to its functional genomics technology, while doing biological screening and supplying its proprietary antisense compounds and methods for Bristol-Myers to deploy in target validation.

Sequitur also has a target-validation agreement with Procter & Gamble Pharmaceuticals Co., of Cincinnati, and one with Minneapolis-based Discovery Genomics, focused on screening antisense compounds to elucidate gene function in zebrafish. (See BioWorld Today, Oct. 10, 2001, and Sept. 27, 2001.)

Other Sequitur clients include Incyte Genomics Inc., of Palo Alto, Calif.; Amgen Inc., of Thousand Oaks, Calif.; Pharmacia Inc., of Kalamazoo, Mich.; GlaxoSmithKline plc, of London; Genome Therapeutics Corp., of Waltham, Mass.; Vertex Pharmaceuticals Inc., of Cambridge, Mass.; Millennium Pharmaceuticals Inc., of Cambridge, Mass.; and Rigel Pharmaceutical Inc., of South San Francisco.

The journal Science recently voted RNAi the 2002 scientific breakthrough of the year, and the technology was the subject of much buzz at last week's CEO & Investor Conference in New York, sponsored by the Biotechnology Industry Organization.

"Did that catch on or what?" said Carl Feldbaum, BIO's president, at the conference. "I heard it more this week than I have ever before. All of a sudden, there it was."

The technology has a long history, starting in 1997, when a team headed by Andrew Fire of the Carnegie Institution of Washington and Craig Mello of the University of Massachusetts Medical School discovered that, by specially designing RNA with two strands, they could deactivate targeted genes. (See BioWorld Today, May 5, 1999.)

A number of firms have been working quietly in the RNAi field, and only in recent months have their efforts gained headlines. Among the companies is Ribozyme Pharmaceuticals Inc., of Boulder, Colo., which last month entered an agreement for $48 million in financing based on its RNAi efforts. (See BioWorld Today, Feb. 12, 2003.)

Sequitur, Woolf said, has "been around for six years doing target validation," with agreements varying from "small work on one or two genes" to larger, longer deals, with "very flexible" arrangements made as collaborators require them.

With a name derived from the same Latin root as "sequence," Sequitur is focused on commercializing products that inhibit gene expression by targeting RNA sequences. The company inhibits gene expression involved in disease-causing pathways with synthetic RNA oligomers.

Sequitur's RNAi therapeutics program was established in 2001, the same year the deal was signed with Bristol-Myers. "We're primarily using RNAi now in our discovery programs and more so in our therapeutics program," Woolf told BioWorld Today.