Live and Let Die: A New Suicide Gene Therapy Moves to the Clinic

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Live and Let Die: A New Suicide Gene Therapy Moves to the Clinic Richard A Morgan  Molecular Therapy  Volume 20, Issue 1, Pages 11-13 (January 2012) DOI: 10.1038/mt.2011.273 Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

Figure 1 iCasp9 suicide gene therapy system. (Top) Diagram of the gamma-retroviral vector designed to express the iCasp9 suicide gene therapy proteins. The vector uses the viral LTR to drive the expression of a fusion protein containing a mutated (F36V) FKBP12 protein linked (SGSG) to the modified caspase 9 (deleted for activation and recruitment domains). To allow physical isolation of the iCasp9-engineered T cells, the last element in the vector is a truncated version of the human CD19 B-cell surface marker (intracellular signaling domains were removed), which can be used to isolate the engineered T cells with readily available clinical reagents. The DCD19 is linked to iCasp9 via a picornavirus 2A peptide (T2A). (Bottom) Biochemically, the iCasp9 fusion protein induces cell apoptosis and death only after it has been dimerized by addition of the small molecule AP1903. Molecular Therapy 2012 20, 11-13DOI: (10.1038/mt.2011.273) Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions