Objectives: In the fields of tissue engineering, regenerative medicine, and disease modeling the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is gaining in importance. The footprint-free generated patient-specific iPSCs have a tremendous potential as a cell source for the creation of desired types of autologous cells. In this study, the reprogramming of human fibroblasts using synthetic modified messenger RNAs (mRNAs) or self-replicating RNAs (srRNAs) encoding the reprogramming factors was compared.