Retroviral vectors for transducing .beta.-globin gene and .beta.-locus control region derivatives

A retroviral vector for transducing .beta.-globin genes and .beta.-LCR sequences comprising:

• (a) a left and a right long terminal repeat (LTR),
• (b) a tRNA primer binding site for initiation of synthesis of vital minus strand strong-stop,
• (c) a polypurine track primer binding site for initiation of synthesis of viral plus strand strong-stop,
• (d) a packaging signal,
• (e) a .beta.-globin gene, and
• (f) an effective portion of the HS2 enhancer of the .beta.-LCR to achieve transduction and expression of the .beta.-globin gene,
• wherein the DNA sequence of the second intron of the .beta.-globin gene is modified, and complementary/reverse splice-signals or polyadenylation signals of the transduced .beta.-globin gene or .beta.-LCR are modified, or both are modified, to inactivate or remove splicing sites or polyadenylation signals within the vector so that the retroviral vector exhibits stability of proviral transmission upon infection of cell-lines and murine bone marrow cells, viral titer effective to achieve infection of bone marrow cells, and high erythroid expression of the transduced human .beta.-globin gene.