SAN DIEGO, June 20 -- Dharmacon is seeking to set standards for siRNA function, amid an apparent shakeup in its own standard management lineup.
At his presentation to the Beyond Genome conference this week at
First, the company is recommending that researchers use 100 nanomols of siRNA. "We've selected 100 nanomols because what we've found is by the 100 nanomol point, you have reached a plateau of the inherent functionality of any siRNA sequence,"
Secondly, the company is recommending that researchers indicate the percentage of gene knockdown that a particular siRNA effects, using a functionality, or F-standard: So, for example, an F50 would mean 50 percent knockdown, whereas F80 would mean 80 percent knockdown. This measurement is to be taken at the 24 hour time point after the siRNA is introduced into the target cells, and Dharmacon recommends that the amount of knockdown be quantitated using QT-PCR or branch DNA.
Dharmacon itself uses Branch DNA,
The fact that Marshall is out in front promoting this standard for Dharmacon at conferences not only demonstrates his obvious enthusiasm for the technology and the company's desire to become its standard-bearer; it's also a subtle sign that the company is undergoing a shift in leadership, as founder and CEO Stephen Scaringe was conspicuously absent from the conference and unavailable to talk to the press about the company's products.
Scaringe, who started Dharmacon in 1995 to commercialize an RNA oligonucleotide synthesis chemistry he invented under the direction of
Kathrin Heermeier, a senior scientist at Aventis, presented on the unique siRNA solution her group has developed: siRNA molecules of 21 to 23 nucleotides with 2'5' over
Interestingly, Heermeier's group has, like Dharmacon, found that 100 nanomols of oligos is optimal. The group is using these siRNAs to knock down active genes in chondrocytes, cartilage cells that play an important role in osteoarthritis.
Dimitri Samarsky from Sequitur also discussed his company's efforts at designing an alternative to the standard 21-25 base-pair siRNA. "Not all siRNAs are as innocent" as they seem, he warned. "Some siRNA causes an interferon response." The company's stealth RNAi, he asserted, is longer t
A further alternative to standard siRNA, Benitec's ddRNAi, is moving more directly into the US market: Promega, which holds a sublicense to the recently granted patent around Benitec's ddRNAi for target validation purposes, is initiating a program to further sublicense this technology to various parties. The company does not expect too many pharmas to be lining up yet: but once they begin to develop the drug-like potential of ddRNAi, a DNA molecule that causes siRNA to be produced in the cell, "those companies will come to us to commercially license" the technology, said Richard Schiffereen, director of technology and market development for Promega.