Adenoviruses for control of gene expression
AssigneeAdVec, Inc.
InventorsFrank L. Graham, Martina Anton, Silvia Bacchetti, Ping Wang, Michael A. Rudnicki, William J. Muller
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Abstract
The invention claims a class of adenovirus vectors for delivering recombinases to a large number of cells of different origins, and methods for regulating the expression of a gene in transfected mammalian cells in culture and in cells of transgenic animals, comprising infecting said cells with an Ad vector encoding a recombinase whose target site is present at or adjacent to the gene, wherein the action of the recombinase regulates the expression of said gene.
Claims24
A recombinant vector comprising an adenovirus genome which comprises:
- (a) foreign DNA encoding a site-specific recombinase, wherein said DNA is operably linked to a promoter that is functional in mammalian cells;
- and
- (b) a modified adenovirus region comprising a modification which renders said vector incapable of forming viable viral particles in host cells which do not provide adenovirus gene products encoded by said modified adenovirus region in the absence of said modification.
An adenovirus vector which comprises DNA encoding a site-specific recombinase operably linked to a promoter functional for expressing said DNA in a mammalian cell.
A method for inducing expression of a gene product, comprising:
- (a) infecting a mammalian cell with a first adenoviral vector, wherein said vector encodes said gene product and comprises target sites of a site-specific recombinase;
- (b) infecting said mammalian cell with a second adenoviral vector, wherein said second adenoviral vector has a gene encoding said site-specific recombinase, and wherein said site-specific recombinase is expressed in said cell;
- (c) maintaining said cell for a time and under conditions sufficient for recombination between said target sites mediated by said recombinase;
- and
- (d) detecting expression of said gene product;
- wherein said recombination results in an induction of gene expression.
A method for inhibiting expression of a gene product which comprises:
- (a) infecting a mammalian cell with a first adenoviral vector, wherein said vector encodes said gene product and comprises target sites of a site-specific recombinase;
- (b) infecting said mammalian cell with a second adenoviral vector, wherein said second adenoviral vector has a gene encoding said site-specific recombinase, and wherein said site-specific recombinase is expressed in said cell;
- (c) maintaining said cell for a time and under conditions sufficient for recombination between said target sites mediated by said recombinase;
- and
- (d) detecting expression of said gene product;
- wherein said recombination results in an inhibition of gene expression.
A method of site-specific recombination in mammalian cells which comprises:
- (a) providing a nucleic acid with target sites of a site-specific recombinase in said mammalian cells;
- (b) infecting said cells with an adenovirus vector encoding said site-specific recombinase;
- wherein said recombinase is expressed in said cells thereby inducing site-specific recombination at the target sites.
A method for controlling gene expression in mammalian cells which comprises:
- (a) providing a nucleic acid with target sites of a site-specific recombinase operably linked to a gene the expression of which is to be controlled in said mammalian cells;
- (b) infecting said cells with an adenovirus vector encoding said site-specific recombinase;
- wherein said recombinase is expressed in said cells thereby controlling the expression of said gene.
Dependencies are inferred from the claim text.