RNAi Is Getting Use in Target Validation

Even though therapeutic applications of RNAi (RNA interference) are far in the future, there is already an siRNA (small interfering RNA) market in target validation work. Navigant Consulting reports in a recent study that RNAi can potentially meet the need for high-throughput gene suppression. The technology, as Navigant senior consultant Alek Bituin says, is maturing.

Navigant sees the siRNA market, estimated at $60 million for 2004, as both rapidly growing and evolving. By 2009, siRNA technology might garner $246 million in sales. The leading technology categories involve the molecules themselves and the vehicles used to get them into cells:

• RNA oligonucleotides, which are siRNA molecules that are synthesized chemically;
• DNA-based siRNA, in which DNA templates are ferried into cells and siRNAs are produced in vivo;
• Transfection reagents that permit nucleic material to be absorbed by cells.

Currently, the siRNA market for target validation is "relatively immature and volatile," according to the Navigant. RNA oligonucleotides--chains of nucleic acid building blocks or nucleotides that can be chemically synthesized--dominate the market, but both DNA-based siRNA and transfection reagents are likely to encroach on oligonucleotides.

Bituin says that, although the debate over the efficacy of DNA-based vectors versus oligonucleotides is not over, the market is shifting toward vectors as the technology becomes more validated. Those products are less expensive and, at times, easier to work with. The idea companies pursue is to integrate RNAi into a target validation package for their customers.

For example, Dharmacon founder Stephen Scaringe, together with Marvin Caruthers of the University of Colorado, Boulder, developed 2´-ACE RNA chemistry as a new way to synthesize RNA. The company began shipping in 1996 and was positioned for RNAi in the late 1990s. Fisher Scientific acquired Dharmacon earlier this year for $80 million. The company offers reagents as well as designed siRNA duplexes targeting human genes. One customer this year has been Bayer. Dharmacon has also just aligned itself with Genospectra to offer a new kind of assay that not only silences genes but also measures the degree of silencing achieved.

Qiagen offers siRNA synthesized with proprietary chemistry during which the monomers are protected and then deprotected at the end of synthesis. Ambion just launched an RNAi library for the Drosophila genome together with Cenix, another RNAi company. Ambion was founded by Matt Winkler from the University of Texas, Austin, to fill his and others' need for reagents for RNA applications.

Navigant's Bituin believes that the technology is moving toward high-throughput applications. "Everyone wants to ramp it up, to apply it to various assay and array technologies," he says. "That is what is going to be driving the market in the future." For now, Dharmacon holds a leading 27% market share, but Navigant predicts that Ambion and Qiagen will increase their presence by 2009. "Qiagen and Ambion are poised for this kind of high-throughput application better than Dharmacon and some of the others are," Bituin says.