Suppression of endogenous immunoglobulin expression
First Claim
1. A method for selective suppression of endogenous immunoglobulin production in B-cells of a non-human transgenic animal carrying an exogenous immunoglobulin translocus, comprising selectively expressing at least one suicide gene in B-cells producing an endogenous immunoglobulin of said non-human transgenic animal, but not in B cells producing an exogenous immunoglobulin, whereby B cells producing the endogenous immunoglobulin are depleted, and production of the endogenous immunoglobulin is suppressed, without suppressing the production of said exogenous immunoglobulin.
1 Assignment
0 Petitions
Accused Products
Abstract
The invention provides a novel approach for the suppression of endogenous antibody expression in non-human transgenic animals genetically engineered to express one or several human or humanized immunoglobulin transloci. Endogenous immunoglobulin expression in transgenic non-human animals is suppressed by selective expression of a suicide gene like a toxin only in B-cells expressing endogenous immunoglobulin but not in B-cells expressing human(ized) immunoglobulins. This method allows the dominant expression of transloci coding for humanized or human antibodies in the blood, milk and eggs of transgenic animals.
-
Citations
35 Claims
- 1. A method for selective suppression of endogenous immunoglobulin production in B-cells of a non-human transgenic animal carrying an exogenous immunoglobulin translocus, comprising selectively expressing at least one suicide gene in B-cells producing an endogenous immunoglobulin of said non-human transgenic animal, but not in B cells producing an exogenous immunoglobulin, whereby B cells producing the endogenous immunoglobulin are depleted, and production of the endogenous immunoglobulin is suppressed, without suppressing the production of said exogenous immunoglobulin.
- 18. A transgenic expression construct comprising a first transgene further comprising a human or humanized immunoglobulin heavy and/or light chain translocus, a self-cleaving peptide and a recombinase.
- 19. A transgenic expression construct comprising a second transgene further comprising a suicide gene that is under the control of a B-cell specific promoter, and is flanked by recombination sites recognized by a recombinase.
-
20. A transgenic expression construct comprising:
-
a first transgene further comprising a human or humanized immunoglobulin heavy and/or light chain locus, a self-cleaving peptide and a recombinase, and, a second transgene further comprising a suicide gene that is under the control of a B-cell specific promoter, and is flanked by recombination sites recognized by said recombinase.
-
Specification