Cystic fibrosis (CF) is the most common lethal monogenic recessive disease in the caucasian population. Over 1900 mutations are known in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, but the most common mutation is the F508del resulting in misfolding of the CFTR protein. Until today, classical gene therapy trials have not been successful in CF patients, and currently approved CFTR modulators are only effective in a minority of CF patients. In contrast, stem cell-based approaches offer new perspectives for diseases like CF. Besides their almost unlimited proliferation and differentiation potential, human induced pluripotent stem cells (hiPSCs) can easily undergo genetic modification. Thus, patient-derived hiPSCs represent a suitable cell source for autologous ex-vivo gene therapy approaches to cure CF. In addition to cell replacement therapies, these cells might serve as a basis for patient-specific drug and toxicology screenings of CFTR modulators in vitro. Our strategy comprises the establishment of patient-specific hiPSCs, the targeted ex-vivo correction of individual CFTR mutations and the differentiation of the iPSCs into CFTR expressing cells. Generation of hiPSCs from somatic cells of CF patients was already successful and genetic correction of these mutated iPSCs was performed by two different gene targeting strategies based on homologous recombination via Zinc-Finger- or TAL-effector nucleases. For proof of concept, we are aiming at the differentiation of non-disease specific human embryonic stem cells (ECS, as control) and of uncorrected and corrected CF hiPSCs into CFTR expressing cells. During differentiation of the hESC line, increasing levels of CFTR mRNA and of mature CFTR protein were detectable. CFTR mRNA expression was verified in differentiating non-corrected and gene-corrected CF hiPSCs as well. Current work is focused on the generation of CFTR reporter cell lines, facilitating monitoring of CFTR expression, optimisation of the differentiation protocol and characterisation of the CFTR positive cells.