Nucleic acid vectors comprising DNase I hypersensitive sites

摘要

The present invention provides 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 present invention also provides for the transgenic animals which contain these recombinant nucleic acid vectors. 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. According to various embodiments of the invention, the vectors may be used to create transgenic animals or to transfect cells in culture. 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.