Ungulates with Genetically Modified Immune Systems
AssigneeRevivicor, Inc.
InventorsKevin Wells, David Ayares
Life of this patent
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Abstract
The present invention provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional endogenous immunoglobulin loci. The present invention also provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which express xenogenous, such as human, immunoglobulin loci. The present invention further provides ungulate, such as porcine genomic DNA sequence of porcine heavy and light chain immunogobulins. Such animals, tissues, organs and cells can be used in research and medical therapy. In addition, methods are provided to prepare such animals, organs, tissues, and cells.
Claims14
A targeting vector comprising:
- (a) a first nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 28 or 31;
- (b) a selectable marker gene;
- and (c) a second nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 28 or 31, which does not overlap with the first nucleotide sequence.
A transgenic ungulate that lacks any expression of functional endogenous immunoglobulins.
A transgenic ungulate that expresses a xenogenous immunoglobulin loci or fragment thereof, wherein the immunoglobulin is expressed from an immunoglobulin locus that is integrated within an endogenous ungulate chromosome.
A method of producing xenogenous antibodies, the method comprising the steps of:
- (a) administering one or more antigens of interest to an ungulate whose cells comprise one or more artificial chromosomes and lack any expression of functional endogenous immunoglobulin, each artificial chromosome comprising one or more xenogenous immunoglobulin loci that undergo rearrangement, resulting in production of xenogenous antibodies against the one or more antigens;
- and (b) recovering the xenogenous antibodies from the ungulate.
The method of claim 8, wherein the immunoglobulin loci undergo rearrangement in a B cell.
An isolated nucleotide sequence comprising porcine heavy chain immunoglobulin or fragment thereof, wherein the heavy chain immunoglobulin includes at least one joining region and at least one constant immunoglobulin region or an ungulate kappa light chain immunoglobulin locus or fragment thereof.
A targeting vector selected from a heavy chain targeting vector comprising:
- (a) a first nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 29 or at least 17 contiguous nucleic acids homologous to SEQ ID No 30;
- (b) a selectable marker gene;
- and (c) a second nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 29 or at least 17 contiguous nucleic acids homologous to SEQ ID No 30, which does not overlap with the first nucleotide sequence;
- and a light chain targeting vector comprising:
- (a) a first nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 28 or 31;
- (b) a selectable marker gene;
- and (c) a second nucleotide sequence comprising at least 17 contiguous nucleic acids homologous to SEQ ID No 28 or 31, which does not overlap with the first nucleotide sequence.
Dependencies are inferred from the claim text.