DESCRIPTION

Since Shinya Yamanaka published the epoch-making paper in 2006, the induced pluripotent stem cells(iPSCs) has become one of the most promising techniques in regenerative medicine. Like embryonic stem cells(ESC), iPS Cells can be differentiated into any tissues. Compared with ESC, iPSC is easier to attain, immune rejection-free, and ethical issue-free.

However, Further application of human induced pluripotent stem cells(iPSCs) in tranlational medicine requires the concerns of two problems: the specificity of directional differentiation and the safety of the transplant. Here we design a new device which can spontaneously select hepatocytes from iPS differentiated cell mass and prevent potential carcinogenesis. Based on the high level of miRNA-122 in normal hepatocytes but not in other cell types or hepatoma cells, our device can detect endogenous miRNA-122 level and then turn on an exogenous apoptosis pathway when the level in cells is low. Tetracycline induction system is also introduced to our device in order to turn on the selection at the right time. Remarkably, using the tet-off system, our device may open the possibility for transplant cells to self-safeguard from potential carcinogenesis in vivo, without taken any medicine in the long term. Besides, combining the special properties of the suicides genes that we used, it is even possible to design a simpler device to achieve our goal.

For the teams in the future to design novel circuits in gene therapy, we also construct a toolkit, including several suicide genes, which we named “Deathly Hollows”, and other easy-to-use regulatory parts.