Method for modulating expression of exogenous genes in mammalian systems, and products related thereto
AssigneeThe Salk Institute for Biological Studies
InventorsRONALD M. EVANS, DAVID NO, ENRIQUE SAEZ
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Abstract
In accordance with the present invention, there are provided various methods for modulating the expression of an exogenous gene in a mammalian subject employing modified ecdysone receptors. Also provided are modified ecdysone receptors, as well as homomeric and heterodimeric receptors containing same, nucleic acids encoding invention modified ecdysone receptors, modified ecdysone response elements, gene transfer vectors, recombinant cells, and transgenic animals containing nucleic acids encoding invention modified ecdysone receptor.
Claims34
A method for modulating the expression of an exogenous gene in a mammalian subject containing:
- (i) a DNA construct comprising said exogenous gene under the control of an ecdysone response element;
- and
- (ii) a modified ecdysone receptor which, in the presence of a ligand therefor, and optionally in the further presence of a receptor capable of acting as a silent partner therefor, binds to said ecdysone response element;
- said method comprising administering to said subject an effective amount of a ligand for said modified ecdysone receptor;
- wherein said ligand is not normally present in the cells of said subject;
- and wherein said ligand is not toxic to said subject.
A method of inducing the expression of an exogenous gene in a mammalian subject containing:
- (i) a DNA construct comprising an exogenous gene under the control of an ecdysone response element,
- (ii) DNA encoding a modified ecdysone receptor under the control of an inducible promoter;
- wherein said modified ecdysone receptor, in the presence of a ligand therefor, and optionally in the further presence of a receptor capable of acting as a silent partner therefor, binds to said ecdysone response element, and
- (iii) a ligand for said modified ecdysone receptor;
- said method comprising subjecting said subject to conditions suitable to induce expression of said modified ecdysone receptor.
A method of inducing expression of an exogenous gene in a mammalian subject containing a DNA construct containing said exogenous gene under the control of an ecdysone response element, said method comprising introducing into said subject:
- a modified ecdysone receptor;
- and
- a ligand for said modified ecdysone receptor,
- wherein said receptor, in combination with a ligand therefor, and optionally in the further presence of a receptor capable of acting as a silent partner therefor, binds to said ecdysone response element, activating transcription therefrom.
A method for the expression of a recombinant product detrimental to a host organism, said method comprising:
- transforming suitable host cells with:
- (i) a DNA construct encoding said recombinant product under the control of an ecdysone response element, and
- (ii) DNA encoding a modified ecdysone receptor;
- growing said host cells in suitable media;
- and
- inducing expression of said recombinant product by introducing into said host cells ligand(s) for said modified ecdysone receptor, and optionally a receptor capable of acting as a silent partner for said modified ecdysone receptor.
A pharmaceutically acceptable formulation comprising at least one ecdysteroid and a pharmaceutically acceptable carrier.
A pharmaceutically acceptable formulation consisting essentially of at least one ecdysteroid and a pharmaceutically acceptable carrier.
A kit comprising at least one ecdysteroid and a pharmaceutically acceptable carrier therefor.
Dependencies are inferred from the claim text.