ERYTHROID-SPECIFIC GENE EXPRESSION SYSTEM

摘要

The present invention relates to the synthesis of proteins of interest, other than α-globin or β-globin, in erythroid tissues of transgenic non-human animals and erythroid cell lines. It is based on the discovery that two of the five hypersensitive sites of the β-globin locus are sufficient to result in high level expression of associated transgenes. The present invention also provides for novel recombinant nucleic acid vectors which may be used to produce proteins of interest, other than α-globin or β-globin, 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 hypersensitive sites associated with the β-globin locus together with the gene of interest. Because the proteins of interest are produced in non-human animals, they are free of such human pathogens as hepatitis virus and human retroviruses, including human immunodeficiency virus (HIV) and human T-cell leukemia virus (HTLV). Finally, the invention provides methods for treating a patient suffering from either a hemoglobinopathy or high cholesterol.