Dec. 10, 2013
/PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced the presentation of new pre-clinical data demonstrating therapeutic levels of gene modification in non-human primates (NHPs) from 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 a specific genomic site in the liver with a single systemic treatment, potentially providing curative treatments for a range of monogenic diseases such as hemophilia and lysosomal storage disorders (LSD) including 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 55
Annual Meeting of the American Society of Hematology (ASH) which is being held in
"These data provide proof of concept for this broadly applicable genome editing strategy by demonstrating that our process is scalable to large animals and by validating the use of the albumin safe harbor as a site for expression of therapeutic proteins," said
. D. Phil., Sangamo's vice president of research and chief scientific officer. "We have further optimized Sangamo's ZFN system and demonstrated that a single systemic treatment enables stable liver-specific production of replacement protein. Early data in primates suggest that we can achieve circulating levels of protein above the threshold for therapeutic effect, which we believe are sufficient for the correction of a range of monogenic diseases. Our data demonstrate expression of replacement enzymes for multiple different proteins, including those deficient in lysosomal storage disorders, which serves 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 active exclusively in the liver. The albumin promoter is highly active, continuously producing large amounts of albumin protein (approximately 15g/day) which is in excess of the body's requirements. With such a large capacity for protein production, targeting and co-opting a very small percentage of the albumin gene's production capacity is sufficient to safely produce the needed replacement protein at therapeutically relevant levels with no significant effect on albumin production. The study was performed as part of Sangamo's collaboration with Shire and in the laboratory of
Katherine A. High
, M.D., director of the Center for Cellular and Molecular Therapeutics at The Children's Hospital of
. Dr. High is a Howard Hughes Medical Institute Investigator, and Professor of Pediatrics at the Perelman School of Medicine at the
University of Pennsylvania
"These data represent an important milestone in the progress of our monogenic disease programs towards the clinic," stated
, Sangamo's president and chief executive officer. "Our In Vivo Protein Replacement Platform is a highly leverageable and disruptive application of our ZFN-mediated genome editing technology and can potentially be applied to any disease-relevant gene where enabling the liver to provide a stable source of corrective replacement protein will be therapeutic. The NHP data presented at ASH represent a significant de-risking step and provide important proof of concept and validation for this entire strategy."
The data were presented in an oral presentation: