Non-human animals expressing humanized c1q complex
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsBrinda PRASAD, Naxin TU, Karolina MEAGHER, Lynn MACDONALD, Andrew MURPHY, Sean STEVENS
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Abstract
Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.
Claims92
A genetically modified non-human animal comprising in its genome a nucleic acid encoding a chimeric C1q polypeptide, wherein the nucleic acid comprises a non-human nucleic acid sequence and a human nucleic acid sequence, wherein the chimeric C1q polypeptide is selected from the group consisting of a chimeric C1qa polypeptide, a chimeric C1qb polypeptide, and a chimeric C1qc polypeptide, and wherein the chimeric C1q polypeptide comprises a globular head domain that is substantially human and an N-terminal stalk-stem region that is substantially non-human.
The genetically modified non-human animal of any of the preceding claims, wherein the chimeric C1q polypeptide comprises a non-human C1q signal peptide, optionally an endogenous non-human C1q signal peptide.
A method of making a genetically modified non-human animal, comprising modifying the genome of a non-human animal to comprise a nucleic acid encoding a chimeric C1q polypeptide, wherein the nucleic acid comprises a non-human nucleic acid sequence and a human nucleic acid sequence, wherein the chimeric C1q polypeptide is selected from the group consisting of a chimeric C1qa polypeptide, a chimeric C1qb polypeptide, a chimeric C1qc polypeptide, and a combination thereof, and wherein the chimeric C1q polypeptide comprises a globular head domain that is substantially human and an N-terminal stalk-stem region that is substantially non-human.
A chimeric C1q polypeptide comprising a globular head domain that is substantially human and an N-terminal stalk-stem region that is substantially non-human, wherein the chimeric C1q polypeptide is selected from the group consisting of a chimeric C1qa polypeptide, a chimeric C1qb polypeptide, and a chimeric C1qc polypeptide.
An isolated nucleic acid encoding a functional chimeric C1q polypeptide comprising a non-human mammal nucleic acid sequence and a human nucleic acid sequence, wherein the human nucleic acid sequence encodes substantially the globular head domain of a human C1q polypeptide and the non-human nucleic acid sequence encodes substantially the N-terminal stalk-stem region of a cognate non-human C1q polypeptide, and wherein the C1q polypeptide is selected from a C1qa polypeptide, a C1qb polypeptide or a C1qc polypeptide.
An isolated nucleic acid encoding a chimeric non-human mammal C1q protein, comprising one or more of a first, second or third nucleotide sequences, wherein:
- a. the first nucleotide sequence encodes a chimeric C1qa polypeptide,
- b. the second nucleotide sequence encodes a chimeric C1qb polypeptide, and
- c. the third nucleotide sequence encodes a chimeric C1qc polypeptide,
- wherein each of the first, second, and third nucleotide sequences comprises a non-human mammal nucleic acid sequence and a human nucleic acid sequence, wherein the human nucleic acid sequence encodes substantially the globular head domain of a human C1qa, C1qb, and C1qc polypeptide, respectively, and the non-human nucleic acid sequence encodes substantially the N-terminal stalk-stem region of a cognate non-human C1q polypeptide C1qa, C1qb, and C1qc polypeptide, respectively.
A cell comprising an isolated nucleic acid of claim 73 or 74.
Dependencies are inferred from the claim text.