Sigma-Aldrich Corporation and Sangamo BioSciences, Inc. announced a research and license agreement to provide Roche with non-exclusive, worldwide rights for the use of its proprietary zinc finger nuclease (ZFN) technology to develop cell-lines and transgenic animals that have targeted modifications in a specified gene in a specified species. Roche also has an option to obtain an exclusive, worldwide license for the commercial use of such ZFN-generated transgenic animals in the production of therapeutic and diagnostic products.

The research phase of the agreement will be conducted in collaboration with both Sangamo and Sigma-Aldrich, Sangamo's exclusive licensee of ZFN technology for high-value research reagents.

"There is growing appreciation of the value of ZFN technology as a rapid, reliable and highly specific tool for modifying genes in eukaryotic cells and whole organisms," said David Smoller, Ph.D., president of Sigma-Aldrich's Research Biotech Business Unit. "We are excited to be working with Sangamo to provide Roche with high-value ZFN reagents for the generation of transgenic animals. ZFN technology promises to enable the generation of a variety of transgenic models of human disease, expediting drug development and production."

"Roche is a leading global healthcare company with an established reputation of innovation. We are pleased to provide them with our ZFN technology which provides a cutting-edge approach for disease research," said Edward Lanphier, Sangamo's president and chief executive officer. "The frequency and precision of ZFN-mediated genome editing, in combination with the ability to design ZFNs against potentially any gene, opens up the possibility of more easily generated transgenic animals of any species."

Zinc finger DNA-binding proteins (ZFPs) are the dominant class of naturally occurring transcription factors in organisms from yeast to humans. Transcription factors, which are found in the nucleus of every cell, bind to DNA to regulate gene expression. Though there are many kinds of transcription factors, only ZFPs are amenable to engineering and precise targeting of a particular gene or genes of interest. ZFNs are engineered forms of ZFPs that also contain a nuclease component which can facilitate modification of a target gene of interest.

"The power of ZFN technology was recently demonstrated in a study published in Nature Biotechnology," said Philip Gregory, D.Phil., Sangamo's Vice President for Research. "Using ZFNs in zebrafish, a widely recognized system for human disease modeling and in vivo drug discovery, resulted in the generation of fish in which the ZFN-targeted gene has been eliminated or 'knocked out'. Apart from the mouse, the majority of other animals including zebrafish have historically lacked methods for precision targeted mutagenesis. This publication demonstrates that ZFNs present a powerful solution to this problem with application across virtually any species for any gene."

Under this agreement, Sangamo will provide a non-exclusive, worldwide research license for the use of its proprietary ZFN technology in the development of transgenic animals. In this phase Roche will pay research fees, including research maintenance fees and research event payments. If Roche elects to exercise its option for an exclusive commercial license it will owe Sangamo an option license fee, additional payments upon the achievement of certain clinical development events and royalties on sales of therapeutic and diagnostic products developed by Roche using the ZFN-modified animals.