Paradoxical effects of Zim3, a CRISPRi effector, on human iPSC-cardiomyocyte electrophysiology

We show that Zim3, when used as Zim3-KRAB-dCas9 effector in interference CRISPR, without any guide RNAs, paradoxically upregulates key cardiac ion channel genes in human induced pluripotent stem-cell-derived cardiomyocytes, iPSC-CMs, responsible for healthy resting membrane potential, repolarization of the action potential and electrical transmission of signals. These were found to yield expected functional enhancements consistent with a more mature iPSC-CM phenotype, with potentially desirable properties.