HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells

Figure 6

Establishment of universally compatible immune nonresponsive human iPSCs by genome editing. Mismatches at the HLA DR (representative HLA class II) locus reveal the greatest impact on the development of an alloimmune response against transplanted organs such as the heart, kidney, and lung. Transcription activator-like effector nucleases (TALENs) were designed for selective removal of HLA DR expression. The TALENSs completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDFs). Dendritic cells derived (differentiated) from HLA DR knockout iPSCs did not express HLA DR and reduced CD4⁺ T cell activation. These engineered iPSCs may have resolved the problem of immune rejection and provided a novel clinical application of derivatives.