Gyongy, Istvan

Hacibekiroglu, Sabiha

Kim, Christopher

Li, Chengjin

Liang, Qin

Mileikovsky, Maria

Monetti, Claudio

Nagy, Andras

Nagy, Kristina

Neely, Eric J

Shutova, Maria V

Sung, Hoon-Ki

Yang, Huijuan

Zhang, Puzheng

The advent of human pluripotent cell lines holds enormous promise for the development of cell therapies to treat degenerative disease. Safety, however, is a crucial pre-condition for clinical application. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes1; however, none of these efforts quantitatively define safety. Here, we show a concept for the protection of a suicide transgene system from inactivation and its realisation withgenome engineering strategies. The strategy behind our fail-safe (FS) design is to create a transcriptional link between the suicide gene herpes simplex virus-thymidine kinase (HSV-TK) and a cell division essential gene, Cyclin-Dependent Kinase 1 (CDK1). Furthermore, we add a quantitative measure to cell therapy safety as the function of the cell number needed for a therapy and the type of genome editing performed. Even with the highly conservative estimates describedhere, we anticipate that our solution and the quantification of safety will rapidly accelerate the entry of cell-based medicine to the clinic

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Generating a link between a cell division and suicide gene provides a measure and solution for cell therapy safety

https://www.pure.ed.ac.uk/ws/files/74615405/Gyongy.pdf

Generating a link between a cell division and suicide gene provides a measure and solution for cell therapy safety

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