Genentech licenses Sangamos ZFP technology for protein production

Under a non-exclusive research and commercial licence agreement, Genentech will gain access to the ZFP technology, while Sangamo will design and engineer ZFP nucleases (ZFNs) for evaluation and potential use by Genentech in generating mammalian cell lines with novel characteristics for protein pharmaceutical production. Genentech will pay Sangamo an upfront fee, an ongoing technology access fee and certain other payments contingent on achievement of milestones related to the ZFN research and to the development and commercialisation of products manufactured using a modified cell line created with the ZFN technology. No further financial details were disclosed. ZFNs are engineered forms of zinc finger DNA-binding proteins that also contain a nuclease component. This component can induce modification of a target gene of interest. The technology has applications both in facilitating the efficient generation of production cell lines with altered traits and in gene modification for therapeutic purposes. Sangamo already has a number of enabling technology agreements with companies such as Pfizer, Medarex, Novo Nordisk, Novartis, Amgen and Kirin Brewery for the use, provision or evaluation of the ZFP system for the enhanced production of antibodies and protein pharmaceuticals. These include cell lines engineered with ZFP nucleases or with ZFP transcription factors (TFs) designed to recognise a specific DNA sequence. On the therapeutic front, Sangamo has supplied companies such as LifeScan (Johnson & Johnson) with ZFP TFs to aid in the development of new treatments for diabetes in the emerging field of regenerative medicine. Sangamo is also pursuing its own therapeutic programmes with sequence-specific ZFP transcription factors and nucleases. The most advanced of these is SB-509, an injectable formulation of plasmid DNA that encodes a ZFP transcription factor designed to upregulate the vascular endothelial growth factor A (VEGF-A) gene. The compound is in an ongoing Phase II clinical trial for mild to moderate diabetic neuropathy. Late last month Sangamo launched a second Phase II trial involving repeat administration of SB-509 in diabetics with 'blocked nerves' or unmeasurable nerve conduction velocity (NEV) in at least one of the nerves of the leg. The company was also recently awarded a $950,000 grant by the Michael J Fox Foundation for Parkinson's Research to fund development of a ZPF transcription factor activator of glial-derived neurotrophic factor or GDNF for the treatment of Parkinson's disease. Sangamo's earlier-stage development programmes include ZFNs for therapeutic gene modification in a variety of monogenic diseases, such as X-linked severe combined immunodeficiency (SCID) and haemophilia, and in infectious diseases such as HIV. ZFPs are the dominant class of naturally occurring transcription factors in organisms ranging from yeast to humans. Transcription factors, which are found in the nucleus of every cell, bind to DNA to regulate gene expression. While there are many kinds of transcription factors, only zinc finger DNA-binding proteins are amenable to engineering and precise targeting to a particular gene or genes of interest, Sangamo notes.