C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/85 (2006.01) A61K 9/66 (2006.01) A61K 35/12 (2006.01) C07K 14/62 (2006.01) C12M 3/00 (2006.01) C12N 5/10 (2006.01) C12N 5/16 (2006.01) C12N 11/04 (2006.01) C12N 15/11 (2006.01) C12N 15/54 (2006.01) C12P 21/02 (2006.01) C12P 21/08 (2006.01)
Patent
CA 2248638
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.
L'invention se rapporte à des compositions et à des procédés d'inhibition des enzymes hexokinase dans des cellules mammaliennes. L'invention se rapporte notamment à des protéines qui stimulent la production de tréhalose-6-phosphate et à leurs gènes respectifs; à des ribozymes spécifiques de l'hexokinase et à des gènes codant ces produits de recombinaison; et à des agents qui réduisent de façon compétitive l'activité de l'hexokinase en délogeant, p.ex., l'hexokinase des mitochondries, et à leurs gènes respectifs. Ce groupe d'agents comprend des hexokinases inactives et des fragments de celles-ci qui conservent les fonctions de liaison mitochondriale et les chimères hexokinase-glucokinase qui substituent également l'activité de la glucokinase à celle de l'hexokinase. L'invention se rapporte aussi à des cellules mammaliennes comprenant ces inhibiteurs d'hexokinase, à des procédés de fabrication de ces cellules et à divers procédés in vitro et in vivo d'utilisation des cellules avec une diminution de l'activité de l'hexokinase.
Becker Thomas C.
Han He-Ping
Newgard Christopher B.
Normington Karl D.
Thigpen Anice E.
Bereskin & Parr
Betagene Inc.
Board Of Regents The University Of Texas System
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