Cell fate conversion by mRNA

It was more than five decades ago when cellular reprogramming was first shown by somatic cell nuclear transfer. These seminal experiments show that somatic cells can revert to pluripotency by somatic cell nuclear transfer, proving the totipotency of their genome. Through later studies we learned that somatic cell fate is mainly driven by a specific set of transcription factors and solidified by epigenetic mechanisms, which can be reverted by reprogramming activities in oocytes or embryonic stem cells. The knowledge gained in the past half a century culminated in the breakthrough discovery of induced pluripotency by Yamanaka and Takahashi in 2006 [1]. They demonstrated that terminally differentiated cells can return to an embryonic-like pluripotent state (termed induced pluripotent stem cells (iPSCs)) by forced expression of four transcription factors (Oct4, Sox2, Klf4 and c-Myc) [1]. iPSC technology has since spurred a plethora of studies aimed at understanding the mechanism of reprogramming, modeling human diseases and developing cell-based therapies for degenerative conditions.Despite great enthusiasm and effort, iPSC-related research is hampered by the fact that iPSC generation is a slow and inefficient process, and that most iPSC derivation protocols entail modifications of the host genome. The most widely adopted method for generating iPSCs relies on integrating retroviral vectors. The process takes approximately 4 weeks and only 0.01 to 0.1% of the cells become iPSCs. In addition, there are serious concerns regarding the safety of these virally derived iPSCs. The integrated proviruses may cause insertional mutagenesis, bias the differentiation potential of iPSCs if not silenced, and lead to tumor formation once reactivated during the differentiation process [2]. People have tried to avoid these issues by generating transgene-free iPSCs using different strategies, including non-integrative vectors, excisable vectors, and cell-penetrating proteins. The DNA-based