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NCI s Gene Silencing Section Working with Qiagen on siRNAs, Building Other Initiatives

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The Gene Silencing Section of the National Cancer Institute's Center for Cancer Research has been collaborating on siRNA reagents with Qiagen under a research collaboration signed earlier this year, RNAi News has learned.

Separately, Qiagen inked a similar deal this week with Institut Curie (see story in this issue).

According to the CCR's website, the partnership gives the Gene Silencing Section, an RNAi research group established by the NCI in 2004 (see RNAi News 1/30/2004), access to synthetic siRNAs targeted towards genes associated with cancer and related processes.

"On one level, it's a very basic research collaboration. On another, it's to develop a great set of tools for cancer researchers," Eric Lader, Qiagen's associate director for research and development who heads the collaboration on the company's side, told RNAi News last month.

Headed by Natasha Caplen, the GSS is using these siRNAs to delineate the role of key pathways involved in cancer and related processes -- in both independent and collaborative studies -- and for the identification and validation of new anti-cancer targets, according to the website.


"On one level, it's a very basic research collaboration. On another, it's to develop a great set of tools for cancer researchers."

"The NCI is getting siRNA design expertise from us [as well as] physical material," such as siRNAs, Lader said. Caplen has been functionally testing them in model systems of cancer, using, for example, primary cancer cells and growing cells in semi-solid media, he added.

Qiagen, meanwhile, is in the midst of a large siRNA validation project, in which it is testing whether its siRNAs can knock down 7,000 druggable human genes in a defined cell type. In exchange for providing reagents, Lader said, Qiagen has access to Caplen's data, which is derived from experiments in "more esoteric cell types" than the established cell lines the company has been using.

Caplen's work "feeds back into our validation project," and can also help the company develop better products such as transfection reagents and a robot that it sells for cell culture handling and transfections, he said.

According to Lader, Qiagen's collaboration with the GSS grew out of the company's April 2002 acquisition of Xeragon, of which Caplen was a customer.

"We re-located Xeragon here to Maryland, [and] we are just up the road from the NIH," where company officials can facilitate meetings to discuss data and RNAi approaches with the agency, he said. Now with the formal agreement in place, discussions occur much more frequently. "We are always in close contact with each other," he said. Additionally, Caplen is now on Qiagen's scientific advisory board for RNAi.

"The relationship with Natasha [and Qiagen] started off as one of a customer and it's changed to where we share data on siRNA design and homology analysis. [Her] biologist's viewpoint in terms of how these genes work helps us [improve our] designs," Lader said.

Caplen was not available to comment on the current status of the work of the GSS because she is planning to publish some of the group's results in the near future, according to an NCI press officer.

However, the CCR website lists some of the section's recent activities, including the development of an infrastructure to characterize siRNAs from the Qiagen collaboration on a "relatively high throughput basis" at the RNA level.

In addition, it is developing "highly sensitive and quantitative" protein-based assays to assess the effects of siRNAs on the protein level. This project is a collaboration with the Antibody Production and Purification Unit at CCR and with John Weinstein at CCR's Laboratory of Molecular Pharmacology.

Caplen's lab is also developing optimized protocols for the transfer of synthetic siRNAs into a wide range of cancer-relevant cell lines and their use in 3D-cell culture models.

Further, the GSS has initiated a number of studies to investigate the interaction of RNAi and cellular drug responses. The aim of these is to understand the mechanism of action, and targets, of anticancer drugs.

Moreover, GSS has "recently initiated" a research program that uses shRNA screens to study "specific functional endpoints." The website invites CCR investigators interested in the program to contact either Caplen or Konrad Huppi, a staff scientist in the CCR's Basic Research Laboratory, according to an NCI website.

Finally, GSS is developing a number of collaborative projects investigating the role of miRNAs in cancer. In collaboration with Robert Stephens at the Advanced Biomedical Computer Center at NCI-Frederick, the group is analyzing miRNA target interactions using bioinformatics. It is also developing several collaborations with CCR investigators study miRNA expression profiles.

-- Julia Karow ([email protected])

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