RICHMOND, Calif., Dec. 10, 2012 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced the presentation of new pre-clinical data demonstrating the successful application of its In Vivo Protein Replacement Platform. Based on Sangamo's zinc finger DNA-binding protein (ZFP) genome-editing technology, the platform enables the permanent production of therapeutic proteins from the liver with a single systemic treatment, potentially providing curative treatments for a range of monogenic diseases including hemophilia and lysosomal storage diseases (LSD) such as Gaucher, and Fabry disease. Such diseases are currently treated by regular infusions of protein or enzyme replacement therapy
(ERT) throughout the patient's life. The data were presented at the 54thAnnual Meeting of the American Society of Hematology (ASH) which is being held in Atlanta.
"These data provide proof-of-concept for this broadly applicable genome editing strategy," said Philip Gregory. D. Phil., Sangamo's vice president of research and CSO. "We show that a single systemic treatment enables stable liver-specific production of human Factor IX protein, the clotting factor absent in hemophilia B, reaching or exceeding 100% of normal circulating levels. In addition, our data in multiple lysosomal storage diseases serve to demonstrate the potential of this approach for a broad range of other monogenic diseases."
Sangamo's In Vivo Protein Replacement Platform makes use of a highly expressed and liver specific genomic "safe-harbor site" that can be edited with ZFP nucleases (ZFNs) to accept and express any therapeutic gene and thus permanently produce high levels of the missing protein with a single treatment. The gene encoding albumin, the most abundant protein in blood serum, was chosen as a safe harbor site because it is highly expressed exclusively in the liver, continuously producing large amounts of albumin protein (approximately 15g/day). With such a large capacity for protein production, targeting and co-opting a very small percentage of the body's albumin production capacity is sufficient to safely produce the needed replacement protein at therapeutically relevant levels. The study was performed in collaboration with the laboratory of Katherine A. High
, M.D., director of the Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia. Dr. High, a Howard Hughes Medical Institute Investigator, is also a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.
"This platform demonstrates our ability to leverage our ZFN technology across multiple disease areas and enables us to rapidly expand our ZFP Therapeutic pipeline," stated Edward Lanphier, Sangamo's president and chief executive officer. "As these presentations at ASH demonstrate, our ZFN gene-editing platform has broad utility with the potential to provide a disruptive and broadly leverageable therapeutic approach to a variety of diseases with unmet medical needs. Our In Vivo Protein Replacement Platform has the potential to impact any disease-relevant gene where enabling the liver to provide a stable source of corrective replacement protein will be therapeutic."
The data were presented in an oral presentation:
Abst. #751 In Vivo Genome Editing of Liver Albumin for Therapeutic Gene Expression: Rescue of Hemophilic Mice Via Integration of Factor 9 (Oral Session: 801)
Monday, December 10, 2012: 4:30 PM
Scientists demonstrated efficient ZFN-mediated gene correction in an adult mouse model of hemophilia B with a single systemic administration of ZFNs and a donor DNA sequence encoding the corrected human Factor IX gene. Efficient modification of the albumin locus to insert a correct copy of the Factor IX gene was achieved with a single treatment resulting in the production of robust stable levels of circulating Factor IX protein that normalize clotting times in hemophilic mice.
In addition, data were presented demonstrating the broad utility of this method for the potential treatment of a wide range of monogenic diseases. In these studies, this same albumin-specific ZFN strategy was used in combination with appropriately designed donor DNA sequences encoding a diverse range of protein factors including alpha-galactosidase which is deficient in Fabry disease, beta-glucosidase (Gaucher disease), Iduronate-2 Sulfatase (Hunter disease) and alpha-L-Iduronidase (Hurler disease).
In a second study presented at the meeting, Sangamo's ZFP technology was used to investigate the role of DNA structure in regulation of the beta-globin gene.
Abst. # 280 Controlling Long-Range Genomic Interactions to Reprogram the Beta-Globin Locus
(Oral Session: 503)
Monday, December 10, 2012: 7:45 AM
Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic® for the treatment of HIV/AIDS. Sangamo's other therapeutic programs are focused on monogenic diseases, including hemophilia, Huntington's disease and hemoglobinopathies such as sickle cell anemia and beta-thalassemia. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). Engineering of ZFPs that recognize a specific DNA sequence enables the creation of sequence-specific ZFP Nucleases (ZFNs) for gene modification and ZFP transcription factors (ZFP TFs) that can
control gene expression and, consequently, cell function. Sangamo has entered into a strategic collaboration with Shire AG to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases and 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 www.sangamo.com.
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 human monogenic diseases, including the treatment of hemophilia B and other monogenic 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 BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.
SOURCE Sangamo BioSciences, Inc.