GEiGS solutions were edited in the genome of iPSCs, targeting miRNA scaffolds expressed differentially between iPSC and monocytes/macrophages. Following isolation of iPSC clones successfully edited on both miRNA alleles, they were in vitro differentiated into monocytes and then macrophages. Analysis of B2M silencing at iPSC and iPSC-derived monocyte/macrophage stages demonstrates programmable cell type-specific GEiGS activity.