Artemis Pharmaceuticals GmbH and its strategic partner, Exelixis Inc., teamed with Sangamo BioSciences Inc. to apply the latter company's zinc finger DNA binding protein technology to the rapid creation of conditional knockout mutations in mice for accelerated target validation.

"We want to reduce two things to practice which are not yet available," Peter Stadler, CEO of Cologne, Germany-based Artemis, told BioWorld International. One is to alleviate the current bottleneck in the generation of knockout mice by creating a rapid development method. Stadler declined to put a figure on the extent of the reduction the partners hope to achieve, but the aim, he said, is "to bring this to a new level of time scale." This should also lead to a parallel fall in costs.

The second goal is to create conditional mutations, enabling researchers to switch a particular gene on and off during the life of its host. "The charm of the methodology is if you combine the zinc finger protein expression system with an inducible gene switch, it allows you to turn expression on or off," Stadler said.

Sangamo, of Richmond, Calif., has pioneered the engineering of zinc finger proteins that can recognize and bind specific sequences within individual genes, and hence control transcription. Under the alliance, it will supply Artemis with proteins that modulate the expression of known genes. Artemis is responsible for all the mouse mutagenesis work at its facility in Cologne, while South San Francisco-based Exelixis, a minority shareholder in the German firm, is supplying its genomics and bioinformatics expertise. A possible extension of the project to other model systems is also under consideration, said Stadler.

The partners will provide access to the technology on a contract research basis, said Stadler. Artemis will also use it to functionally validate internally generated targets. The company has drug discovery programs in both promoting and inhibiting angiogenesis, for peripheral cardiovascular disease and cancer, respectively, and in bone and cartilage disease, and other cardiovascular diseases such as arrhythmia and congestive heart failure. It also is engaged with Exelixis and an unnamed partner in programs on neurodegenerative diseases and diabetes.

Artemis, which raised DM 36 million (US$16 million) in April, embarked on a large-scale zebrafish genetic screening project in collaboration with the Max Planck Institute for Developmental Biology, of Tuebingen, Germany, and other partners, in March. This is now generating between 80 and 100 new mutations per week, said Stadler. The partners aim to produce 5,500 mutants by March. "So far we are on track and it is very, very promising," Stadler said.

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