Genetically modified non-human animal with human or chimeric GITR
AssigneeBiocytogen Pharmaceuticals (Beijing) Co., Ltd.
InventorsYuelei Shen, Yanan Guo, Yang Bai, Jiawei Yao, Rui Huang, Lei Zhao, Meiling Zhang
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Abstract
The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) glucocorticoid-induced TNFR-related protein (GITR), and methods of use thereof.
Claims23
A genetically-modified, non-human mammal whose genome comprises at least one chromosome comprising a replacement of a portion of the endogenous GITR gene with a portion of the human GITR gene, wherein the replacement creates a sequence encoding a humanized GITR protein comprising a humanized GITR extracellular region operably linked to an endogenous regulatory element at the endogenous GITR gene locus in the at least one chromosome, wherein the mammal detectably expresses the humanized GITR protein on the surface of activated T-cells.
A genetically modified rodent or a progeny thereof, whose genome comprises a replacement of a portion of the endogenous GITR gene with a portion of the human GITR gene, wherein the replacement creates a sequence encoding a humanized GITR protein comprising a humanized extracellular region operably linked to an endogenous regulatory element at the endogenous GITR gene locus in the at least one chromosome, wherein the mammal detectably expresses the humanized GITR protein on the surface of activated T-cells, wherein the genetically modified rodent is made by a method comprising the steps of:
- modifying genome of an embryo of a rodent by CRISPR with sgRNAs that target SEQ ID NO:
- 1 and SEQ ID NO:
- 11, wherein the portion of the endogenous GITR gene is replaced with the portion of the human GITR gene;
- and
- transplanting the embryo to a recipient rodent to produce the genetically-modified rodent, whose genome comprises the replacement of the portion of the endogenous GITR gene with the portion of the human GITR gene.
A genetically-modified, non-human mammal whose genome comprises at least one chromosome comprising a replacement of a portion of the endogenous GITR gene encoding the extracellular region of the endogenous GITR protein with a nucleic acid sequence encoding the corresponding portion of the extracellular region of the human GITR protein, wherein the mammal detectably expresses a humanized GITR protein on the surface of activated T-cells.
Dependencies are inferred from the claim text.