Methods and compositions for inhibiting hexokinase

Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of...

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435 691, 435 647, 435194, 4353201, 435455, 435456, 435458, 435463, 536 232, 536 234, 935 13, 935 14, 935 32, 935 57, 935 60, 935 70, 935 71, C12N 510, C12N 1585, C12N 1556, C12N 1562

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058917179

ABSTRACT:
Disclosed are compositions and methods for inhibiting hexokinase enzymes in mammalian cells. Specifically provided are proteins that stimulate the production of trehalose-6-phosphate and their respective genes; hexokinase-specific ribozymes and genes encoding such constructs; and agents that competitively reduce hexokinase activity, e.g., by displacing hexokinase from mitochondria, and their respective genes. The latter group of agents includes inactive hexokinases and fragments thereof that retain mitochondrial binding functions and hexokinase-glucokinase chimeras that further substitute glucokinase activity for hexokinase activity. Mammalian cells including such hexokinase inhibitors, methods of making such cells and various in vitro and in vivo methods of using cells with reduced hexokinase activity are also described herein.

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