Genetically modified non-human animal with human or chimeric PD-L1
AssigneeBiocytogen Pharmaceuticals (Beijing) Co., Ltd.
InventorsYuelei Shen, Yang Bai, Yanan Guo, Rui Huang, Xiaofei Zhou, Chaoshe Guo
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Abstract
This disclosure relates to genetically modified animal expressing human or chimeric (e.g., humanized) programmed death-ligand 1 (PD-L1, PDL1, or B7-H1), and methods of use thereof. In one aspect, the disclosure relates to genetically-modified, non-human animals whose genome comprises at least one chromosome comprising a sequence encoding a human or chimeric programmed death-ligand 1 (PD-L1).
Claims11
A genetically-modified mouse whose genome comprises at least one chromosome comprising a nucleotide sequence encoding a chimeric programmed death-ligand 1 (PD-L1) at an endogenous PD-L1 gene locus, wherein the chimeric PD-L1 comprises SEQ ID NO:
- 33, wherein the mouse expresses the chimeric PD-L1 on the surface of one or more spleen cells after the genetically modified mouse is challenged by anti-CD3 antibody.
A genetically modified mouse or a progeny thereof, wherein the genetically modified mouse is made by a method comprising the steps of:
- modifying genome of an embryo of a mouse by CRISPR with sgRNAs that target SEQ ID NO:
- 1 and SEQ ID NO:
- 11 to introduce a fragment of human PD-L1 gene, wherein an endogenous PD-L1 gene locus in the genome of the embryo is modified;
- and transplanting the embryo to a recipient mouse to produce the genetically-modified mouse, wherein the genetically-modified mouse expresses a chimeric PD-L1 comprising a fragment of human PD-L1 protein on the surface of one or more spleen cells after the genetically-modified mouse is challenged by anti-CD3 antibody.
A genetically-modified mouse whose genome comprises at least one chromosome comprising a sequence encoding a human PD-L1 at an endogenous PD-L1 gene locus, wherein the sequence encoding the human PD-L1 is operably linked to an endogenous regulatory element at the endogenous PD-L1 gene locus in the at least one chromosome, wherein the mouse expresses a human PD-L1 on the surface of one or more spleen cells after the genetically modified mouse is challenged by anti-CD3 antibody.
Dependencies are inferred from the claim text.