Targeted biallelic integration of an inducible Caspase 9 suicide gene in iPSCs for safer therapies.

ABSTRACT: Drug-inducible suicide systems may help to minimize risks of human induced pluripotent stem cell (hiPSC) therapies. Recent research challenged the usefulness of such systems since rare drug-resistant subclones were observed. We have introduced a drug-inducible Caspase 9 suicide system (iCASP9) into the AAVS1 safe-harbor locus of hiPSCs. In these cells, apoptosis could be efficiently induced in vitro. After transplantation into mice, drug treatment generally led to rapid elimination of teratomas, but single animals subsequently formed tumor tissue from monoallelic iCASP9 hiPSCs. Very rare drug-resistant subclones of monoallelic iCASP9 hiPSCs appeared in vitro with frequencies of ∼ 3 × 10^-8. Besides transgene elimination, presumably via loss of heterozygosity (LoH),

SUBMITTER: Wunderlich S 

PROVIDER: S-EPMC9234009 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature