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Sangamo BioSciences Announces Publication in Nature of Gene Correction Strategy for Alpha 1-Antitrypsin Deficiency

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Monday, October 17, 2011

Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced the publication of a preclinical study demonstrating highly specific, functional correction of the alpha 1-antitrypsin (A1AT) gene defect in patient-derived induced pluripotent stem cells (iPSCs) using zinc finger nucleases (ZFNs).

The study, published in Nature, further highlights the precision and broad applicability of ZFN-based genome-editing for the development of ZFP Therapeutics® for the treatment of monogenic diseases.

"These data demonstrate the potential of combining human iPSCs with ZFN-driven gene correction to generate differentiated cell-based therapies," stated Philip Gregory, D. Phil., Sangamo's vice president of research and chief scientific officer. "Importantly, analysis of the entire coding sequence of a ZFN-corrected iPSC line revealed that the only modification attributable to ZFN activity was the intended repair of the A1AT gene. This demonstrates the singular specificity that can be achieved using Sangamo's ZFP technology."

The work was carried out in collaboration with scientists at the Wellcome Trust Sanger Institute, the University of Cambridge, U.K., DNAVEC Corporation of Japan, and several laboratories in Europe. The study was published as an Advance Online Publication in Nature on October 12, 2011 (

"Our precise ZFN genome-editing technology enables Sangamo to modify any target gene of interest," said Edward Lanphier, Sangamo's president and chief executive officer. "As this study demonstrates, our platform can generate novel ZFP Therapeutic options for diseases that have a well-defined genetic cause. In addition to our ZFN clinical programs in HIV, addressing unmet medical needs such as hemophilia and other monogenic diseases is a focus of our therapeutic pipeline."

The paper entitled, "Targeted Gene Correction of Alpha 1-Antitrypsin Deficiency in Induced Pluripotent Stem Cells" describes highly specific and efficient ZFN-mediated correction of a defective human A1AT gene in iPSCs derived from skin cells from individuals with alpha 1-antitrypsin deficiency (A1ATD). The A1AT gene encodes a protein that is made in the liver and protects the lungs and liver from damage. A1ATD is the most common inherited metabolic disease of the liver, and is the result of a single mutation in the A1AT gene. iPSCs can be reprogrammed to develop into a wide range of tissues. Reintroduction of gene-corrected iPSCs into patients with an identified gene defect may provide a treatment approach to genetic disease.

iPSCs that had undergone ZFN-mediated correction were differentiated in vitro into hepatocyte-like cells (the main cell type affected in the disease) that secreted active A1AT protein at levels comparable to normal adult hepatocytes. Transplanted ZFN-corrected iPSCs were found to "colonize" livers of a mouse model system. Sequence analysis of the coding genome of a ZFN-corrected hiPSC line revealed that the sole change in the genome attributable to ZFN activity was the repair of the A1AT gene, demonstrating the precision of the modification.

About Sangamo

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. Sangamo has a Phase 1 / 2 clinical trial and two ongoing Phase 1 clinical trials to evaluate the safety and efficacy for the treatment of HIV/AIDS as well as a Phase 1 trial for the treatment for recurrent glioblastoma multiforme. Other therapeutic programs are focused on Parkinson's disease, monogenic diseases, neuropathic pain and nerve regeneration. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as 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. Sangamo is also developing sequence-specific ZFP Nucleases (ZFNs) for gene modification. Sangamo has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the company's website at

ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.

This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, the potential of ZFNs to treat h uman monogenic diseases such as hemophilia and other rare diseases, research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the initiation and completion of stages of our clinical trials, whether the clinical trials will validate and support the tolerability and efficacy of ZFNs, technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our competitors. For a more detailed discussion of these and other risks, please see Sangamo's SEC filings, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

Elizabeth Wolffe, Ph.D. 
+1-510-970-6000, ext. 271
Source: Sangamo BioSciences, Inc.
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