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AssigneesBoard of Regents, The University of Texas System, Betagene, Inc.
InventorsChristopher B. Newgard, He-Ping Han, Karl D. Normington
Estimating the term…
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.
A mammalian host cell comprising an inhibitor of a low K.sub.m hexokinase, the inhibitor selected from:
An engineered host cell that secretes insulin in response to glucose, the cell comprising an inhibitor of a low K.sub.m hexokinase, the inhibitor selected from:
An engineered mammalian host cell derived from a cell that forms secretory granules, the cell secreting insulin in response to glucose and comprising a first recombinant gene selected from the group consisting of hexokinase IV, insulin and GLUT-2 and a second recombinant gene selected from the group consisting of:
A composition comprising an inhibitor of a low K.sub.m hexokinase, characterized as:
Dependencies are inferred from the claim text.