DISCRIPTION

Since Shinya Yamanaka published the epoch-making paper in 2006, the induced pluripotent stem cell(iPScell) has become one of the most promising techniques in regenerative medicine. Like embryonic stem cells(ESC), iPS Cells can be differentiated into any tissues. And comparing with ESC, iPSC is easier to attain, immune rejection-free, and without ethical issues.

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 hepatocyte from iPS differentiated cell mass and prevent potential carcinogenesis. Based on the high level of miRNA-122 in normal hepatocyte but not in other cell types or cancerous hepatic 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. Noteworthily, with the tet-off system, our device may opens the possibility of transplant self-safeguarding from potential carcinogenesis in vivo without any medicine in the long term. And combing the special properties of the suicides genes that we used, it is even possible to design even simpler device to achieve our goal.

For the future teams 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.