Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1995-06-06
1998-06-16
Chambers, Jasemine C.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
800 2, 435 691, 4351723, 4353201, 4352402, 435 696, 935 11, 935 62, C12N 1500, C12N 1585, C12N 1579
Patent
active
057668841
ABSTRACT:
The present invention relates to the synthesis of functional human hemoglobin and other proteins in erythroid tissues of transgenic non-human animals and erythroid cell lines. It is based on the discovery that two of the five hypersensitivity sites of the .beta.-globin locus are sufficient to result in high level expression of human .alpha.- or .beta.-globin transgenes. The present invention also provides for novel recombinant nucleic acid vectors which may be used to produce .alpha.-globin as well as other proteins of interest in quantity in the red blood cells of transgenic animals or cell cultures of erythroid lineage. The vectors of the invention comprise at least one of the major DNase I hypersensitivity sites associated with the .beta.-globin locus together with a gene of interest. In a specific embodiment of the invention, a vector which comprises two DNase I hypersensitivity sites together with the human .alpha.-globin gene is used to create transgenic animals which produce human .alpha.-globin protein in erythroid tissues, including red blood cells. In a preferred specific embodiment of the invention, transgenic animals are created which comprise human .alpha.-globin and .beta.-globin genes, each under the transcriptional influence of two .beta.-globin locus DNase hypersensitivity sites; these transgenic animals express human hemoglobin in their erythroid tissues, and can be used to produce human hemoglobin in quantity.
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Behringer Richard R.
Brinster Ralph L.
Palmiter Richard D.
Ryan Thomas M.
Townes Tim M.
Chambers Jasemine C.
Hauda Karen M.
The Board of Regents of the University of Washington
The Trustees of the University of Pennsylvania
The UAB Research Foundation
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