AT3 gene editing in iPSCs for hereditary thrombophilia

Transplant of induced pluripotent stem cell (iPSC)-derived hepatocytes with CRISPR-mediated correction of a hereditary antithrombin deficiency-causing mutation in AT3 could help treat thrombophilia.

Peripheral blood mononuclear cells from a patient with severe antithrombin deficiency were reprogrammed into iPSCs, in which the patient's AT3 mutation was corrected via a CRISPR–Cas9 editing strategy that incorporated a fluorescent marker to select clones with successful gene integration. These cells subsequently underwent Cre-LoxP genome editing to remove that selection marker, followed by sequencing to identify corrected, marker-free clones, which were differentiated into hepatocytes. ...