Sangamo BioSciences Announces Presentation of New Data from ZFP Therapeutic® Program in Hemophilia B at American Society for Hematology Meeting
Studies Expand Potential of ZFN-Mediated Genome Editing as a Therapeutic Modality
PR NewswirePress Release: Sangamo BioSciences, Inc. – Tue, Dec 13, 2011 7:00 AM EST
RICHMOND, Calif. , Dec. 13, 2011 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO - News) announced the presentation of new data demonstrating the ability to permanently correct a disease gene in an adult mouse model of hemophilia B using systemic delivery of zinc finger nucleases (ZFNs) at the 53nd Annual Meeting of the American Society of Hematology (ASH).
"We have demonstrated functional correction of a human gene for the clotting factor, Factor IX, with a single, systemic administration of ZFNs in an animal model of disease," said Geoff Nichol , M.B, Ch.B., Sangamo's executive vice president of research and development. "Our approach enables permanent correction of the genetic defect responsible for hemophilia B. This circumvents the problems of traditional gene-addition approaches that uncouple the gene from its normal regulatory mechanism and which may result in gene silencing and random gene insertion and potentially lead to malignancy or other unintended consequences."
Abst. No.668 - Robust Factor IX Expression Following ZFN-mediated Genome Editing in an Adult Mouse Model of Hemophilia B (Oral Session: 801)
In this study, 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. Stable levels of protein made from the corrected human gene could be measured in the plasma of the treated animals and resulted in the restoration of normal rates of blood clotting for the period of the study. This work expands upon earlier studies, published in Nature*, that demonstrated similar results in neonatal mice. Data described at the ASH meeting demonstrate that growth of liver cells, as is observed in neonates, is not required for efficient ZFN-mediated repair of the human Factor IX gene, substantially expanding the potential of the approach.
The study was conducted in the laboratory of Katherine High , M.D., Investigator, Howard Hughes Medical Institute, Professor of Pediatrics, University of Pennsylvania School of Medicine and Director, Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia , in collaboration with Sangamo scientists.
In a second study presented at the meeting, ZFN gene disruption was used to generate a next generation cancer immunotherapy by enhancing the targeted killing activity and safety profile of the product.
Abst. No. 667 - TCR Gene Editing Results in Effective Immunotherapy of Leukemia without the Development of GvHD (Oral Session: 801)
Cancer immunotherapy uses CD8 T-cells that have been engineered to express high avidity T-cell receptor (TCR) genes isolated from tumor-specific lymphocytes. The engineered CD8 T-cells are then able to attack the tumor. Problems can arise with this approach because the expression of the CD8 T-cell's own TCR gene interferes with expression of the inserted tumor-specific TCR gene. This interaction limits the potency of this cellular therapy but, more importantly, it can also make the cells "self-reactive" leading to graft versus host disease (GvHD).
In this study, ZFNs were used to disrupt the native TCR genes in these tumor-directed CD8 T-cells resulting in an enhanced immunotherapeutic product with potent cancer cell-killing activity and the elimination of GvHD in a mouse model. These studies were performed in the laboratory of Chiara Bonini , M.D., Head of the Experimental Hematology Unit, San Raffaele Hospital, Milan , in collaboration with Luigi Naldini , Head of TIGET, San Raffaele Hospital, and Sangamo scientists.
"We continue to develop our ZFP Therapeutic pipeline and, on the strength of our success in mouse models, have advanced our hemophilia B program into preclinical studies in a large animal model of the disease," stated Edward Lanphier , Sangamo's president and chief executive officer. "As these presentations demonstrate, our ZFN gene-editing platform has broad applicability in that it can be applied to any disease-relevant gene enabling permanent gene modification and has the potential to provide a valuable therapeutic approach to a variety of unmet medical needs."
* Nature. 2011 Jun 26;475 (7355):217-21. doi: 10.1038/nature10177. "In vivo genome editing restores haemostasis in a mouse model of haemophilia".
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