Linking a cell-division gene and a suicide gene to define and improve cell therapy safety

Qin Liang, Claudio Monetti, Maria V Shutova, Eric J Neely, Sabiha Hacibekiroglu, Huijuan Yang, Christopher Kim, Puzheng Zhang, Chengjin Li, Kristina Nagy, Maria Mileikovsky, Istvan Gyongy, Hoon-Ki Sung, Andras Nagy

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Human pluripotent cell lines hold enormous promise for the development of cell-based therapies. Safety, however, is a crucial prerequisite condition for clinical applications. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes1, but none has quantitatively defined the safety level of transplant therapies. Here, using genome-engineering strategies, we demonstrate the protection of a suicide system from inactivation in dividing cells. We created a transcriptional link between the suicide gene herpes simplex virus thymidine kinase (HSV-TK) and a cell-division gene (CDK1); this combination is designated the safe-cell system. Furthermore, we used a mathematical model to quantify the safety level of the cell therapy as a function of the number of cells that is needed for the therapy and the type of genome editing that is performed. Even with the highly conservative estimates described here, we anticipate that our solution will rapidly accelerate the entry of cell-based medicine into the clinic.
Original languageEnglish
Pages (from-to)24
Publication statusPublished - 14 Nov 2018


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