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AssigneeCrystal Bioscience Inc.
InventorsWilliam Don HARRIMAN, Philip A. LEIGHTON
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This disclosure provides, among other things, a transgenic chicken. In some embodiments, the transgenic chicken comprises B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding a heavy chain variable domain in which the CDR3 is in the range of 30-60 amino acids in length and comprises at least 2 cysteine residues; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the heavy chain variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene.
A transgenic chicken comprising B cells in which the endogenous immunoglobulin heavy chain locus comprises:
The transgenic chicken of any prior claim, wherein non-B cells of the chicken comprise the functional immunoglobulin heavy chain gene of (a) and the pseudogenes of (b).
The transgenic chicken of any prior claim, wherein the pseudogenes do not comprise a sequence that corresponds to the CDR3 region of the heavy chain variable domain of (a).
The transgenic chicken of any prior claim, wherein the pseudogenes comprise a sequence that diversifies the coding sequence for the CDR3 region of the heavy chain variable domain of (a) by gene conversion.
The transgenic chicken of any prior claim, wherein the sequences in the pseudogenes that diversify the coding sequence for the CDR3 region of the heavy chain variable domain of (a) by gene conversion encode an amino acid sequence that is in the range of 30-60 amino acids in length and comprises at least 2 cysteine residues
The transgenic chicken of any prior claim, wherein the heavy chain variable domain of (a) is an autonomous heavy chain (AHC) variable domain.
The transgenic chicken of any prior claim, wherein the pseudogenes of (b) encode human germline antibody sequences.
The transgenic chicken of any prior claim, wherein the pseudogenes are 300-600 nucleotides in length.
The transgenic chicken of any prior claim, wherein the endogenous immunoglobulin heavy chain locus encodes a heavy chain that comprises a CH1 deletion.
The transgenic chicken of any prior claim, wherein the genome of the chicken comprises a light chain immunoglobulin gene that has been knocked out.
The transgenic chicken of any prior claim, wherein the genome of the animal comprises a light chain immunoglobulin gene that encodes a truncated light chain that comprises a constant region but not a variable region.
The transgenic chicken of any prior claim, wherein animal is homozygous for the locus.
The transgenic chicken of any prior claim, wherein animal is heterozygous for the locus.
A method comprising:
Dependencies are inferred from the claim text.