"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
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
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
"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
* Nature. 2011 Jun 26;475 (7355):217-21. doi: 10.1038/nature10177. "In vivo genome editing restores haemostasis in a mouse model of haemophilia".
ZFP Therapeutic® is a registered trademark of
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, 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
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