Company has been leveraging ZFP and ZFN technology to develop research tools and therapeutics.
Sangamo BioSciences is offering to sell 6,700,000 shares of its common stock pursuant to an effective shelf registration statement in an underwritten public offering. Barclays Capital is the sole book-running manager in this offering, and Sangamo will grant the underwriter a 30-day option to purchase up to 1,005,000 additional shares.
Sangamo’s technology enables the engineering of a class of DNA-binding proteins called zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence, Sangamo has created ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function. The company is also developing sequence-specific ZFP nucleases (ZFNs) for therapeutic gene regulation and modification.
Sigma-Aldrich exclusively markets Sangamo’s ZFN technology through its CompoZr™ line of products and services. It supplies related research reagents as well as ZFP-modified cell lines for commercial production of protein pharmaceuticals and has rights to certain ZFP-engineered transgenic animals for commercial applications.
Reporting in the July 2009 issue of Science, Sangamo and collaborators said that they had created the first genetically modified rats using the ZFN technology. They used ZFNs to knock out an inserted reporter gene and two native rat genes without causing measurable effects on other genes. Importantly, offspring of the ZFN-mutated rats also carried the modifications, demonstrating that the genetic changes were permanent and heritable.
ZFNs are engineered proteins that induce double-strand breaks at specific sites in an organism’s DNA. Such double-strand breaks stimulate the cell’s natural DNA-repair pathways and can result in site-specific changes in the DNA sequence. ZFNs have reportedly been used to knock out specific genes in fruit flies, worms, cultured human cells, and zebrafish embryos.
ZFNs are also currently in clinical trials. The most advanced is SB-509, which is in a Phase IIb trial in patients with diabetic neuropathy. Sangamo is also evaluating the compound for the treatment of ALS, spinal cord and traumatic brain injury, as well as stroke. It also has a Phase I/II trial and two ongoing Phase I trials with SB-728-T for HIV/AIDS treatment as well as a Phase I study in recurrent glioblastoma multiforme with SB-313.
Most recently, in April CHDI Foundation signed on to use ZFP technology to develop a therapeutic for Huntington disease. The aim is to develop a ZFP TF capable of altering expression of the mutated huntingtin gene.