“…Viruses and/or integrative methods usually have the highest reprogramming efficiency but the lowest degree of safety (e.g., insertional mutagenesis and presence of viral components). In contrast, safer approaches such as the use of small molecules (e.g., RepSox, valproic acid, and tranylcypromine [26–29]), microRNAs (e.g., miR-302~367 cluster, miR-371~373 cluster, miR-17 family [30–34]), or metabolites (e.g., sodium butyrate, ascorbic acid, and forskolin [29, 35, 36]) either have less reprogramming efficiency or usually cannot induce pluripotency alone and are therefore frequently used in combination(s) with classical reprogramming factors [29, 37, 38]. Transfection of mRNAs that code for the classical reprogramming factors have also been used to induce pluripotency in somatic cells [39, 40], but due to their inherent instability, the mRNAs need to be transfected repeatedly.…”