The development deal with Sangamo could be worth in excess of $35m (€25m), with an initial payment of $13.75m to be followed by milestone payments of up to $22m as well as royalty payments on product sales and licensing deals. The collaboration will aim to develop zinc finger DNA binding proteins (ZFPs) for a variety of applications that make use of a ZFPs ability to modify gene expression and cell function. "We believe that Sangamo's ZFP technology could fundamentally alter the way in which research on living cells and organisms is conducted," said Jai Nagarkatti, CEO of Sigma-Aldrich. "By vastly improving the precision and efficiency with which genomes of living organisms can be modified and regulated, ZFPs provide significant potential for both research and development." A zinc finger protein (ZFP) domain can recognise and bind to a variety of functional DNA domains at gene-specific locations. In addition to applications in drug discovery and protein production, Sangamo has been developing these proteins as therapeutic agents by attaching a functional domain that can activate, repress or modify specific genes in a DNA strand to the ZFP binding domain. The company currently has a ZFP therapy in Phase II clinical trials for diabetic neuropathy as well as a Phase I trial for a ZFP peripheral artery disease. The zinc fingers consist of two antiparallel ß sheets, and an a helix that are held together by a zinc ion, in the absence of zinc the domain unfolds and is deactivated. These domains recognise and bind to a 3 base pair sequence and can be 'stitched' together to bind to specific target sequences. This would allow researchers to design ZFPs to bind to target sequences and then alter the function of the genes next to the targets to produce cell lines with silenced genes for use in drug discovery applications or enhance a cell lines ability to produce specific proteins for use as biological drugs.