Abstract
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 with
genome 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 described
here, we anticipate that our solution and the quantification of safety will rapidly accelerate the entry of cell-based medicine to the clinic.
genome 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 described
here, we anticipate that our solution and the quantification of safety will rapidly accelerate the entry of cell-based medicine to the clinic.
Original language | English |
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Number of pages | 24 |
Journal | Nature |
Volume | 563 |
Publication status | Published - 14 Nov 2018 |