It was initially proposed that telomerase alone could immortalize human cells without deleterious effects on the genome. In the recent past, these investigators and other researchers have demonstrated that telomerase can only immortalize epithelial cells that have already escaped from MO, a telomere-independent mortality control parameter. Furthermore, escape from MO is accompanied by inactivation of the p16/Rb tumor suppressor pathway. Knowledge of the effectors of MO (e.g. p16 gene), and of regulators of telomerase (e.g. myc) suggested that binary genetic combinations could significantly effect single-step immortalization. Currently, we lack a novel technique of immortalizing human cells for therapeutic use. The investigators have already conducted preliminary experiments and established single step immortalization of human keratinocytes.
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