From Russia with love

How three scientists from the former Soviet Union are leading teams to discover new therapies for prostate cancer

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ROCKVILLE, Md.—Ariadne will use its bioinformatics software and knowledge integration skills in a joint collaboration with Cellecta Inc. and the Roswell Park Cancer Institute to develop a comprehensive knowledge base of prostate-specific pathway models, under an agreement announced last month.

The project, partially sponsored by a National Cancer Institute (NCI) Small Business Innovation Research (SBIR) Phase I grant, will use Cellecta's siRNA library screening system for a panel of prostate cancer cell lines to identify genes essential for viability of cancer cells. Ariadne will use the data from the siRNA screens and available 'omics data to identify pathways involved and build mechanistic models in support of the genes identified from the siRNA targets in the screen. Roswell Park is contributing its expertise in prostate cancer biology and clinical applications.

Asked how the three-way collaboration came about, Dr. Andrei Gudkov, vice president for basic science at Roswell Park, states, "DECIPHER technology, Cellecta's functional genomics platform, is the best among available shRNA screening techniques and greatly facilitates our ability to identify and validate potential drug targets."

Ariadne, he adds, is also a leader in its field. In addition, as is frequently true in the relatively small world of bioscience research, the team's three leaders have known each other for many years. Gudkov was the mentor of Dr. Ilya Mazo, Ariadne's CEO, when both were at the University of Illinois, Chicago, and all three men are Russian. In fact, they routinely discuss plans and results in the language of their native country.

From the research perspective, Gudkov notes that, "We expect significant benefits from this collaboration." Gudkov says that with the prostate, it is possible to treat the disease without distinguishing cancer from normal cells since the gland is comprised of nonessential cell types. Suppressing a single gene that results in androgen blockage could effect a sort of biochemical castration that would lead to a cure.

"We anticipate rapid progression into drug discovery and other clinically relevant directions," Gudkov states.

Mazo also emphasizes the importance of collaborative experience, first with Gudkov, but also with Cellecta, with whom his company has worked in the past and built a strong relationship of trust. For Ariadne, the collaboration is part of a company strategy to develop disease-specific databases, notes Mazo. Currently, for example, the company is involved in a multimillion-dollar project with nine European partners.

"The anticipated result of this collaboration is a better understanding of the mechanism of prostate cancer that results in novel targets and biomarkers," says Mazo.

Ultimately, genetic profiling will be a "product," with subscriptions available for various cancer types, he says.

"By leveraging our technical expertise and background in computational biology and disease models, we can continue to provide support in collaborative partnerships with researchers, resulting in new knowledge bases for the drug discovery industry," he adds.

Cellecta will contribute its pooled lentiviral shRNA libraries, says Dr. Alex Chenchik, the company's president and CEO. In one to four months, the company can provide oligo, plasmid or plasmid-plus packaged pooled shRNA libraries designed to target specific sets of genes. The advantages of using Cellecta's screening method incluce the low cost of the technology that uses second-generation, pre-designed validated shRNA libraries.

Cellecta is a privately held contract research company that was founded in April 2006 with a mission to develop the most advanced high-throughput RNAi and peptide screen technologies and their applications for the discovery and functional characterization of novel therapeutic targets and drugs.

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