Viral vectors for prophylaxis and therapy of hemoglobinopathies

A self-inactivating lentiviral vector for inducing expression of human beta-globin in erythrocytes and/or erythrocyte progenitor cells for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual, the lentiviral vector comprising:

• i) a 5′ long terminal repeat (LTR) and a self-inactivating 3′ LTR;
• ii) a first polyadenylation signal;
• iii) at least one promoter;
• iv) a globin gene locus control region (LCR);
• v) an ankyrin insulator element (Ank);
• vi) a Woodchuck Post-Regulatory Element (WPRE);
• vii) a second polyadenylation signal;
• and
• viii) a sequence that is the reverse complement of a sequence encoding modified adult human beta-globin comprising a βT87Q mutation (B-globinM), wherein the sequence encoding the B-globinM comprises a first intron (intron 1) between exon 1 and exon 2, and a second intron (intron 2) between exon 2 and exon 3 of said B-globinM sequence, wherein intron 2 comprises the full-length of the adult human B-globinM intron 2 sequence;
• wherein the lentiviral vector comprises in the 5′ to 3′ direction:
• said 5′ long terminal repeat (LTR), said sequence that is the reverse complement of a sequence encoding modified adult human beta-globin comprising a βT87Q mutation (B-globinM) under the control of said promoter and linked to said first polyadenylation signal, said globin gene locus control region (LCR), said self-inactivating 3′ LTR comprising said ankyrin insulator element (Ank), said Woodchuck Post-Regulatory Element (WPRE), and said second polyadenylation signal.