Targeted biallelic integration of an inducible Caspase 9 suicide gene in iPSCs for safer therapies
Stephanie Wunderlich, Alexandra Haase, Sylvia Merkert, Kirsten Jahn, Maximillian Deest, Helge Frieling, Silke Glage, Wilhelm Korte, Andreas Martens, Andreas Kirschning, André Zeug, Evgeni Ponimaskin, Gudrun Göhring, Mania Ackermann, Nico Lachmann, Thomas Moritz, Robert Zweigerdt, Ulrich Martin
Abstract
. Besides transgene elimination, presumably via loss of heterozygosity (LoH), silencing via aberrant promoter methylation was identified as a major underlying mechanism. In contrast to monoallelic iCASP9 hiPSCs, no escapees from biallelic iCASP9 cells were observed after treatment of up to 0.8 billion hiPSCs. The highly increased safety level provided by biallelic integration of the iCASP9 system may substantially contribute to the safety level of iPSC-based therapies.