Abstract 14013: Direct Comparison of Disease-Specific versus TALEN-Corrected iPSC-Derived Cardiomyocytes from Dilated Cardiomyopathy Patients

Introduction: Recent advances in regenerative medicine for cardiovascular disease (CVD) therapy focus on delivery of autologous induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to recover heart function without immunosuppression. Here, we perform a direct comparison of iPSC-CMs from a healthy individual, a DCM patient, and following genome-correction with transcription activator-like effector nucleases (TALENs) both in vitro and in vivo. Methods & Results: We established patient-specific iPSC-CMs that recapitulate DCM disease-phenotypes in-vitro, including disrupted sarcomeres and impaired Ca2+ handling (p<0.05). We corrected the patient′s DCM-specific mutation R173W in the TNNT2 locus via TALEN-mediated footprint-free genome editing. Isogenic TALEN-corrected iPSC-CMs recovered functional properties comparable to healthy control. Ca2+ transient analysis revealed no significant difference between TALEN-corrected iPSC-CMs and healthy control regarding amplitude (ΔF/F0 4.71±0.55), decay (277.6...