Schlaeger, T.M. et al. Nat. Biotechnol. doi:10.1038/nbt.3070 (1 December 2014).

Schlaeger et al. report a systematic comparison of three methods for reprogramming somatic cells to induced pluripotent stem cells that do not involve incorporation of exogenous DNA into the genome. They reprogrammed human fibroblasts using a Sendai virus–based system, an episomal system, or mRNA-based reprogramming, benchmarking these to integrating viral methods. They report no discernible difference between the methods in terms of pluripotency or differentiation potential of the resulting cells. RNA-based reprogramming is more efficient (when it succeeds), but it has an overall lower success rate than the other methods. Episomal reprogramming generates cells with a slightly higher incidence of karyotypic instability, but this is still lower than that seen with retroviral reprogramming. Cells reprogrammed with Sendai virus require a relatively long time until they are vector free. The most appropriate method will depend on the needs of each laboratory; this analysis should help researchers decide which reprogramming method best meets their needs.