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Turning Silencing Into Therapy

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  • Title: Group Leader, Institute for Chemistry and Biochemistry, Free University of Berlin
  • Education: Habilitation, Free University of Berlin, 2006; Postdoc, Arizona State University; PhD, Technical University Berlin, 1998
  • Recommended by: Muhammed Soheil

Jens Kurreck may have a master's degree in philos-ophy, but his focus has been firmly in the realm of empirical science for more than 10 years.

Kurreck received his doctorate at the Technical University of Berlin, where his research centered on the molecular mechanisms of photosynthesis. After spending a postdoc year in the United States, Kurreck joined Volker Erdmann's lab at the Free University of Berlin. Since 1999, he has led the molecular medicine group in Erdmann's biochemistry lab, where his team investigates the structure and function of RNAi molecules. Just this year, Kurreck completed his habilitation — Germany's post-doctoral qualification for full professor status — and he's now on the search for his first tenure-track position.

It's a good bet that wherever Kurreck ends up professionally, novel findings on the frontlines of RNAi research will likely follow. As a lead investigator in Erdmann's lab, Kurreck's work has already resulted in unique discoveries on two fronts: the use of siRNAs as an antiviral tool and target validation in pain research.

In collaboration with Grunenthal, a Germany-based pharmaceutical com-pany interested in developing new drugs for pain alleviation, Kurreck's team "took a validated target — the vanilloid receptor — and optimized siRNAs and shRNA expression cassettes against it." The idea was to identify silencing molecules capable of reducing pain sensitivity in animal models. The approach was successful, in that the pharma collaborators "observed an analgesic effect of RNAi on the animals," Kurreck says. His team is now looking for new targets using RNAi methods, which Grunenthal plans to use in vivo for validation studies.

Looking ahead

Surveying the years to come, Kurreck hopes RNAi becomes a viable therapeutic option, and believes this is the direction that companies and academics alike are going. However, he does acknowledge that before achieving in vivo applications for these molecules, the RNAi delivery hurdle must be overcome.

His assessment is born of experience. For instance, Kurreck developed an approach for using siRNAs to inhibit a picarnovirus that causes heart muscle infections. To this end, his team developed a vector that simultaneously expresses two shRNAs against the viral gene, reducing the change of escaped viral mutants. The approach has been widely accepted as a means to prevent the emergence of mutant genes upon long-term silencing by RNAi, but Kurreck isn't resting on his laurels. "Together with our cardiology partners, we also have a five- to 10-year prospective plan to [develop] therapeutic approaches for delivery of shRNA cassettes," he says.

Publications of note

In 2003, Kurreck reported an unbiased comparison of antisense and siRNAs, showing that "antisense oligonucleotides are better than conventional phosphorothioates, but siRNAs are even better," he says. It was also in this paper, "Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2'O-methyl RNA, phospho-rothioates and siRNA," that Kurreck's team first selected an efficient siRNA against the vanilloid receptor.

Making of a great scientist

Kurreck's recipe for successful science is simple: one must focus on the project at hand while forging fruitful collaborations. “Definitely an important part [of being a good scientist] is being able to share your enthusiasm with co-workers in the lab in order to create new ideas.”

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