Method of using a transgenic chicken to produce exogenous proteins in its eggs
A transgenic avian containing in its genome an exogenous nucleotide sequence which includes a promoter component and a vector with reduced promoter interference wherein the exogenous nucleotide sequence is integrated into the genome and the avian.
1. A method of using a transgenic chicken to produce an exogenous protein comprising:
providing a transgenic chicken whose genome comprises a self-inactivating avian leukosis viral (ALV) vector encoding an exogenous protein operably linked to a promoter;
obtaining a hard shell egg containing the exogenous protein from the transgenic chicken,
wherein the promoter comprises a nucleic acid sequence that is at least 90% identical to a nucleic acid molecule comprising from 5′ to 3′:
i) an ovalbumin Dnase hypersensitive site (DNS) III consisting of nucleotides 3253-3559 of SEQ ID NO: 22;
ii) an ovalbumin DNS II consisting of nucleotides 5629-6009 of SEQ ID NO: 22;
iii) an ovalbumin DNS I consisting of nucleotides 6359-6659 of SEQ ID NO: 22;
iv) a 5′ UTR-5′ portion from Exon L consisting of nucleotides 6659-6705 of SEQ ID NO: 22;
v) intron A consisting of nucleotides 6706-8294 of SEQ ID NO: 22;
vi) a 5′ UTR-3′ portion from Exon I consisting of nucleotides 8295-8311 of SEQ ID NO: 22;
vii) a 3′ UTR.
2. The method of claim 1 , wherein the exogenous protein is a human protein.
3. The method of claim 1 , wherein the exogenous protein is a therapeutic protein.
4. The method of claim 1 wherein the exogenous protein is selected from the group consisting of erythropoietin, GM-C SF, interferon, fusion protein, CTLA4-Fc fusion protein, growth hormones, cytokines, structural, interferon, lysozyme, β-casein, albumin, α-1 antitrypsin, antithrombin III, collagen, factors VIII, IX, X (and the like), fibrinogen, lactoferrin, protein C, tissue-type plasminogen activator (tPA), somatotropin, chymotrypsin, immunoglobulins, antibodies, immunotoxins, factor VIII, b-domain deleted factor VIII, factor VIIa, factor IX, anticoagulants; hirudin, alteplase, reteplase, tPA- 3 of 5 domains deleted, insulin, insulin lispro, insulin aspart, insulin glargine, long-acting insulin analogs, glucagons, thyroid-stimulating hormone (tsh), follitropin-beta, follicle-stimulating hormone (fsh), pdgh, inf-beta, inf-alpha 1, ifn-alpha 2, inf-beta, inf-beta 1b, ifn-beta 1a, ifn-gamma, ifn-gamma 1b, il-2, il-11, HBsAg, dornase-alpha dnase, beta glucocerebrosidase, tnf-alpha, il-2-diptheria toxin fusion protein, tnfr-lgg fragment fusion protein laronidase, DNAses, alefacept, tositumomab, murine mab, alemtuzumab, rasburicase, agalsidase beta, teriparatide, parathyroid hormone derivatives, adalimumab (lgg1), anakinra, biological modifier, nesiritide, human b-type natriuretic peptide (hbnp), colony stimulating factors, pegvisomant, human growth hormone receptor antagonist, recombinant activated protein c, omalizumab, immunoglobulin E blocker, lbritumomab tiuxetan, ACTH, glucagon, somatostatin, somatotropin, thymosin, parathyroid hormone, pigmentary hormones, somatomedin, luteinizing hormone, chorionic gonadotropin, hypothalmic releasing factors, etanercept, antidiuretic hormones, prolactin, thyroid stimulating hormone, human immunoglobulin polypeptide D region, human immunoglobulin polypeptide J region, human immunoglobulin polypeptide C region, human immunoglobulin light chain, human immunoglobulin heavy chain, an human immunoglobulin heavy chain variable region, and an immunoglobulin light chain variable region.
5. The method of claim 1 further comprising isolating said protein.