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System Biosciences Prepares for Launch of siRNA Library Against 8,500 Human Genes

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As interest in RNA interference research grows, so too has the number of companies selling proprietary siRNA libraries and collections. Now, add System Biosciences to the list — at least in about a week or two, if all goes according to the company’s plan.

SBI was founded in July 2002 by Alex Chenchik, former director of research and development in the gene cloning and analysis section of Clontech Laboratories, which was later acquired by BD Biosciences. The company, which currently employs about seven people, is focused on developing tools for understanding genomic and proteomic function.

One of these tools is the company’s GeneNet library of about 40,000 siRNAs targeting 8,500 characterized human genes, which includes about five siRNAs per gene.

According to Paul Diehl, director of marketing and sales at SBI, the library is, essentially, a heterogenous mixture of siRNAs expressed from a plasmid that can be used to examine the roles of genes. “If you’re looking for apoptosis or resistance to irradiation or a response to a certain type of compound, you subject the cells to whatever [siRNA] selection you want, then the cells that survive have siRNA sequences that are targeting and inhibiting genes that are functionally involved in that pathway,” he told RNAi News.

“It’s a different approach than actually picking an siRNA sequence or sets of genes you are interested in, and seeing what the effect is when you inhibit that gene,” Diehl said. “In this case, you’re doing the reverse — you’re looking at some sort of effect on the cells and trying to identify the genes that are involved in that pathway.

Diehl said that the GeneNet library comes in “pseudoviral particles so that [researchers] can immediately use that to transduce their cells.” Although product issues still have to be worked out, he added, “they’ll [likely] be enough for … three to six transductions per kit.”

According to SBI, the pseudoviral particles are created by co-transfecting an expression vector, which is based on the feline immunodeficiency virus retrovirus and is designed to express either short hairpin RNAs or double-stranded RNAs, along with packaging plasmids into a packaging cell line.

“The lentiviral expression vector contains the genetic elements required for packaging, transduction, stable integration of the viral expression construct into genomic DNA, and expression of the siRNA effector sequence,” according to the GeneNet siRNA library’s protocol. “The lentiviral packaging plasmids provide all of the proteins essential for transcription and packaging of an RNA copy of the expression construct into recombinant viral particles.”

Chenchik noted that in designing the siRNAs, SBI used “sequences [that] are complementary to Affymetrix’s gene probes.” As a result, the GeneNet library is compatible with Affymetrix’s GeneChip arrays, which allows researchers to “analyze all the 40,000 siRNA constructs [from the library] at one time,” he told RNAi News. “We use Affymetrix [GeneChip technology] as a read-out system to analyze populations of siRNAs in cells,” he said.

Chenchik added that SBI has no formal relationship with Affymetrix.

Even though SBI is a small company, it plans on marketing the siRNA library itself, Chenchik told RNAi News. Diehl said that SBI will employ a “standard marketing approach — sending out direct mailings, doing press releases, making people aware of it. We’ll also be doing shows in the fall and doing some seminars here and there,” he added.

Distribution in the US will also be handled by SBI, although the firm does have a network of distributors overseas, including BioCat in Germany, B-Bridge International in Japan, and Cambridge BioScience in the UK.

Diehl said that pricing of the library has not been finalized, but that the company remains committed to ensuring that it will be affordable to the research community. “We’re probably looking at a few thousand dollars,” he said.

Chenchik noted that researchers at the Cleveland Clinic Foundation collaborated with SBI as beta-testers for the GeneNet library, using it to assist them in prostate cancer drug target discovery efforts.

Launch of the GeneNet library is slated for the end of April, “hopefully,” Diehl said.

— DM

 

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