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Rapid and highly efficient reprogramming of cells with RNA

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Research published in the 30th September edition of Cell Stem Cell reports that human induced pluripotent stem cells (hiPSCs) can be rapidly and efficiently derived with messenger RNA (mRNA) 1. This research, from the laboratory of Derrick Rossi shows that daily transfection of differentiated human cells with modified synthetic mRNAs encoding the four canonical Yamanaka factors KLF4, c-MYC, OCT4, and SOX2 can reprogram cells to pluripotency with conversion efficiencies and kinetics substantially superior to established viral protocols. The authors also demonstrate the directed differentiation of RNA-hiPSCs to terminally differentiated muscle cells. The reprogramming of human fibroblasts using exactly this strategy has already been published from the laboratory of David Givol, albeit with reduced efficiency2.

The development of this technique offers clear advantages over previously published techniques which present considerable limitations including viral integration into the genome, very low integration efficiency, risk of genomic recombination or insertional mutagenesis. These synthetic mRNAs are nonintegrating, nonmutagenic and highly controllable, representing a safer and more efficient iPSC technology.

References

1. L. Warren, P.D. Manos, T. Ahfeldt et al. Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA. 10.1016/j.stem.2010.08.012.

2. E.Yakubov, G.Rechavi, S.Rozenblatt et al. Reprogramming of human fibroblasts to pluripotent stem cells by using mRNA of four transcription factors. BBRC 394(2010): 189-193.

 

Also see related news article in Nature Research Highlights.