Gene reactivation by somatic hypermutation
AssigneeCornell Research Foundation, Inc.
InventorsP. Bergsagel, Davide Robbiani
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Abstract
The invention provides an inactivated or attenuated gene functionally linked to a hotspot for somatic hypermutation. Inventive nucleic acids include inactivated genes operatively linked to immunoglobulin gene control elements. Embodiments of the invention include murine models of plasma cell disease and germinal center cell lymphoma.
Claims31
An isolated and purified nucleic acid comprising a gene functionally linked to a hotspot for somatic hypermutation, wherein the nucleic acid further comprises a nucleic acid sequence that inactivates or attenuates the gene.
An isolated and purified nucleic acid comprising an inactivated or attenuated gene, wherein the gene is operatively linked to one or more immunoglobulin gene regulatory elements.
An isolated and purified nucleic acid comprising an inactivated or attenuated gene, wherein the nucleic acid sequence inactivating the gene is within about one to about five nucleotides of a rgyw or a dgyw nucleic acid sequence.
A method of regulating the expression of a gene in a cell, the method comprising
- (a) engineering a gene that is functionally inactive,
- (b) cloning the functionally inactivated gene so as to be operatively linked to control elements that subject the gene to somatic hypermutation, and
- (c) transforming cells with the inactivated gene functionally linked to somatic hypermutation control elements.
Dependencies are inferred from the claim text.