Finally, should reprogrammed cells be considered for clinical (i.e. transplantation) use, the viral gene delivery would have to be replaced with safer methods. It is therefore important to demonstrate that iN cells can be generated using non-integrative gene delivery methods. Adler and coworkers transfected the BAM factors into MEFs using linear poly amido amine and obtained up to 7.6% Tuj1-positive cells with five serial transfections after 10 days [38]. In addition, Meng et al. used adenoviral Brn2, Ascl1 and Ngn2 and obtained a modest 2.9% of reprogramming efficiency [39]. These studies have established that non-integrative gene delivery methods are possible. They also highlight the need for further improvement of the gene delivery systems in order to make the study of iN cells useful.
