The AMRITA project has launched with a small dedicated team as a vanguard. A project to transduce cells with gene therapy vectors designed to recognize and tag senescent cells by virtue of activation of promoters that drive genes such as p16INK4a, beta galactosidase, and alpha-fucosidase is underway thanks to the efforts of AMRITA interns Alison Tang and Lena Meyer. There are no universal biomarkers for cell senescence: p16INK4a is upregulated in some cell types, e.g., fibroblasts and muscle, but not in others such as cardiomyocytes. To reverse senescence in a mammal will require using several different ways to tag and program such cells. We have designed and are building synthetic biology circuits to reverse senescence in selected cells by down-regulating senescent maintenance genes such as p16INK4A, p21, and p38 MAPK. Cells that have been irreversibly damaged will be programmed to self-destruct.
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